Trial Outcomes & Findings for Combination Chemotherapy With or Without Vismodegib in Treating Patients With Advanced Stomach Cancer or Gastroesophageal Junction Cancer (NCT NCT00982592)

NCT ID: NCT00982592

Last Updated: 2016-01-25

Results Overview

PFS is defined as the time from randomization until objective tumor progression or death from any cause and is evaluated per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 124 participants
• Primary outcome timeframe: up to 4 years
• Results posted on: 2016-01-25

Participant Flow

From October 2009 to February 2012, 124 patients were enrolled from multi sites to this study.

Participant milestones

Measure	Arm I (FOLFOX Regimen and Placebo) Patients receive FOLFOX chemotherapy comprising oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil bolus and then IV over 46-48 hours on day 1. Patients also receive placebo PO QD on days 1-14. Courses repeat every 2 weeks in the absence of unacceptable toxicity or disease progression.	Arm II (FOLFOX Regimen and Vismodegib) Patients receive FOLFOX chemotherapy as in arm I. Patients also receive vismodegib PO on days 1-14. Courses repeat every 2 weeks in the absence of unacceptable toxicity or disease progression.
Overall Study STARTED	64	60
Overall Study Treatment Received	63	52
Overall Study COMPLETED	33	27
Overall Study NOT COMPLETED	31	33

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Combination Chemotherapy With or Without Vismodegib in Treating Patients With Advanced Stomach Cancer or Gastroesophageal Junction Cancer

Baseline characteristics by cohort

Measure	Arm I (FOLFOX Regimen and Placebo) n=64 Participants Patients receive FOLFOX chemotherapy comprising oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil bolus and then IV over 46-48 hours on day 1. Patients also receive placebo PO QD on days 1-14. Courses repeat every 2 weeks in the absence of unacceptable toxicity or disease progression.	Arm II (FOLFOX Regimen and Vismodegib) n=60 Participants Patients receive FOLFOX chemotherapy as in arm I. Patients also receive vismodegib PO on days 1-14. Courses repeat every 2 weeks in the absence of unacceptable toxicity or disease progression.	Total n=124 Participants Total of all reporting groups
Age, Continuous	61.5 years n=5 Participants	57.5 years n=7 Participants	60 years n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	21 Participants n=7 Participants	32 Participants n=5 Participants
Sex: Female, Male Male	53 Participants n=5 Participants	39 Participants n=7 Participants	92 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	50 participants n=5 Participants	42 participants n=7 Participants	92 participants n=5 Participants
Race/Ethnicity, Customized Asian	3 participants n=5 Participants	6 participants n=7 Participants	9 participants n=5 Participants
Race/Ethnicity, Customized African American	6 participants n=5 Participants	4 participants n=7 Participants	10 participants n=5 Participants
Race/Ethnicity, Customized Hispanic	4 participants n=5 Participants	8 participants n=7 Participants	12 participants n=5 Participants
Race/Ethnicity, Customized Nor reported	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Region of Enrollment United States	64 participants n=5 Participants	60 participants n=7 Participants	124 participants n=5 Participants

PRIMARY outcome

Timeframe: up to 4 years

Population: Intent-to-treat population

PFS is defined as the time from randomization until objective tumor progression or death from any cause and is evaluated per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

Outcome measures

Measure	Arm I (FOLFOX Regimen and Placebo) n=64 Participants Patients receive FOLFOX chemotherapy comprising oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil bolus and then IV over 46-48 hours on day 1. Patients also receive placebo PO QD on days 1-14. Courses repeat every 2 weeks in the absence of unacceptable toxicity or disease progression.	Arm II (FOLFOX Regimen and Vismodegib) n=60 Participants Patients receive FOLFOX chemotherapy as in arm I. Patients also receive vismodegib PO on days 1-14. Courses repeat every 2 weeks in the absence of unacceptable toxicity or disease progression.
Median Progression-free Survival (PFS)	8.77 months Interval 5.65 to 10.61	8.35 months Interval 5.55 to 10.61

SECONDARY outcome

Timeframe: Up to 4 years

Population: Intent-to-treat population

Defined as the percentage of the patients who had complete response (CR) or partial response (PR) per RECIST 1.1.

Outcome measures

Measure	Arm I (FOLFOX Regimen and Placebo) n=64 Participants Patients receive FOLFOX chemotherapy comprising oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil bolus and then IV over 46-48 hours on day 1. Patients also receive placebo PO QD on days 1-14. Courses repeat every 2 weeks in the absence of unacceptable toxicity or disease progression.	Arm II (FOLFOX Regimen and Vismodegib) n=60 Participants Patients receive FOLFOX chemotherapy as in arm I. Patients also receive vismodegib PO on days 1-14. Courses repeat every 2 weeks in the absence of unacceptable toxicity or disease progression.
Objective Response Rate	44 percentage of patients	37 percentage of patients

SECONDARY outcome

Timeframe: up to 4 years

Population: Intent-to-treat population

Defined as time from randomization day until death from any cause.

Outcome measures

Measure	Arm I (FOLFOX Regimen and Placebo) n=64 Participants Patients receive FOLFOX chemotherapy comprising oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil bolus and then IV over 46-48 hours on day 1. Patients also receive placebo PO QD on days 1-14. Courses repeat every 2 weeks in the absence of unacceptable toxicity or disease progression.	Arm II (FOLFOX Regimen and Vismodegib) n=60 Participants Patients receive FOLFOX chemotherapy as in arm I. Patients also receive vismodegib PO on days 1-14. Courses repeat every 2 weeks in the absence of unacceptable toxicity or disease progression.
Overall Survival	15.38 months Interval 12.32 to 19.52	12.12 months Interval 10.28 to 17.77

SECONDARY outcome

Timeframe: Up to 4 years

Population: All the patients who started the treatment.

Defined as percentage of patients who experienced a toxicity with grade 3 or higher related to the protocol therapy. Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0

Outcome measures

Measure	Arm I (FOLFOX Regimen and Placebo) n=63 Participants Patients receive FOLFOX chemotherapy comprising oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil bolus and then IV over 46-48 hours on day 1. Patients also receive placebo PO QD on days 1-14. Courses repeat every 2 weeks in the absence of unacceptable toxicity or disease progression.	Arm II (FOLFOX Regimen and Vismodegib) n=52 Participants Patients receive FOLFOX chemotherapy as in arm I. Patients also receive vismodegib PO on days 1-14. Courses repeat every 2 weeks in the absence of unacceptable toxicity or disease progression.
Incidence of Toxicities (Grade 3 and Higher) Fatigue	10 percentage of patients	15 percentage of patients
Incidence of Toxicities (Grade 3 and Higher) Thrombosis	11 percentage of patients	14 percentage of patients
Incidence of Toxicities (Grade 3 and Higher) Dehydration	6 percentage of patients	8 percentage of patients
Incidence of Toxicities (Grade 3 and Higher) Neutropenia	32 percentage of patients	50 percentage of patients
Incidence of Toxicities (Grade 3 and Higher) Hypokalemia	5 percentage of patients	10 percentage of patients
Incidence of Toxicities (Grade 3 and Higher) Hyperglycemia	10 percentage of patients	4 percentage of patients
Incidence of Toxicities (Grade 3 and Higher) Neuropathy (sensory)	13 percentage of patients	19 percentage of patients
Incidence of Toxicities (Grade 3 and Higher) Nausea	8 percentage of patients	8 percentage of patients
Incidence of Toxicities (Grade 3 and Higher) Hemorrhage_GI	11 percentage of patients	8 percentage of patients
Incidence of Toxicities (Grade 3 and Higher) Vomiting	6 percentage of patients	8 percentage of patients
Incidence of Toxicities (Grade 3 and Higher) Febrile neutropenia	5 percentage of patients	2 percentage of patients
Incidence of Toxicities (Grade 3 and Higher) Anemia	10 percentage of patients	10 percentage of patients
Incidence of Toxicities (Grade 3 and Higher) Thrombocytopenia	0 percentage of patients	6 percentage of patients
Incidence of Toxicities (Grade 3 and Higher) Hyponatremia	10 percentage of patients	2 percentage of patients

SECONDARY outcome

Timeframe: Up to 4 years

Population: All the patients who started the treatment.

Defined as percentage of patients who experienced a toxicity with grade 1 or 2 (worst grade) related to the protocol therapy. Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0.

Outcome measures

Measure	Arm I (FOLFOX Regimen and Placebo) n=63 Participants Patients receive FOLFOX chemotherapy comprising oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil bolus and then IV over 46-48 hours on day 1. Patients also receive placebo PO QD on days 1-14. Courses repeat every 2 weeks in the absence of unacceptable toxicity or disease progression.	Arm II (FOLFOX Regimen and Vismodegib) n=52 Participants Patients receive FOLFOX chemotherapy as in arm I. Patients also receive vismodegib PO on days 1-14. Courses repeat every 2 weeks in the absence of unacceptable toxicity or disease progression.
Incidence of Toxicities (grades1 and 2) Neuropathy (sensory)	56 percentage of patients	62 percentage of patients
Incidence of Toxicities (grades1 and 2) Fatigue	54 percentage of patients	73 percentage of patients
Incidence of Toxicities (grades1 and 2) Diarrhea	48 percentage of patients	40 percentage of patients
Incidence of Toxicities (grades1 and 2) Nausea	54 percentage of patients	71 percentage of patients
Incidence of Toxicities (grades1 and 2) Dysguesia	16 percentage of patients	42 percentage of patients
Incidence of Toxicities (grades1 and 2) Vomiting	38 percentage of patients	37 percentage of patients
Incidence of Toxicities (grades1 and 2) Anorexia	41 percentage of patients	35 percentage of patients
Incidence of Toxicities (grades1 and 2) Hyperglycemia	41 percentage of patients	37 percentage of patients
Incidence of Toxicities (grades1 and 2) Weight loss	30 percentage of patients	29 percentage of patients
Incidence of Toxicities (grades1 and 2) Leukocytes	57 percentage of patients	46 percentage of patients
Incidence of Toxicities (grades1 and 2) Anemia	51 percentage of patients	60 percentage of patients
Incidence of Toxicities (grades1 and 2) Thrombocytopenia	57 percentage of patients	56 percentage of patients
Incidence of Toxicities (grades1 and 2) Hypoalbuminemia	52 percentage of patients	40 percentage of patients
Incidence of Toxicities (grades1 and 2) Elevated AST	29 percentage of patients	46 percentage of patients

Adverse Events

Arm I (FOLFOX Regimen and Placebo)

Serious events: 24 serious events

Other events: 63 other events

Deaths: 0 deaths

Arm II (FOLFOX Regimen and Vismodegib)

Serious events: 20 serious events

Other events: 52 other events

Deaths: 0 deaths

Serious adverse events

Measure	Arm I (FOLFOX Regimen and Placebo) n=63 participants at risk Patients receive FOLFOX chemotherapy comprising oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil bolus and then IV over 46-48 hours on day 1. Patients also receive placebo PO QD on days 1-14. Courses repeat every 2 weeks in the absence of unacceptable toxicity or disease progression.	Arm II (FOLFOX Regimen and Vismodegib) n=52 participants at risk Patients receive FOLFOX chemotherapy as in arm I. Patients also receive vismodegib PO on days 1-14. Courses repeat every 2 weeks in the absence of unacceptable toxicity or disease progression.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pain: Tumor pain	1.6% 1/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	0.00% 0/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Respiratory, thoracic and mediastinal disorders Pleural effusion (non-malignant)	1.6% 1/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	0.00% 0/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Respiratory, thoracic and mediastinal disorders Pneumonitis/pulmonary infiltrates	1.6% 1/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	0.00% 0/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Vascular disorders Portal vein flow	1.6% 1/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	0.00% 0/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Respiratory, thoracic and mediastinal disorders Pulmonary/Upper Respiratory - Other (Specify, __)MALIGNANT PLEURAL EFFUSION	1.6% 1/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	0.00% 0/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Metabolism and nutrition disorders Sodium, serum-low (hyponatremia)	1.6% 1/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	0.00% 0/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Metabolism and nutrition disorders Potassium, serum-low (hypokalemia)	0.00% 0/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	1.9% 1/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Renal and urinary disorders Renal failure	0.00% 0/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	1.9% 1/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Gastrointestinal disorders Stricture/stenosis (including anastomotic), GI: Stomach	0.00% 0/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	1.9% 1/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Nervous system disorders Syncope (fainting)	1.6% 1/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	1.9% 1/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Vascular disorders Thrombosis/thrombus/embolism	7.9% 5/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	3.8% 2/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Vascular disorders Thrombosis/embolism (vascular access-related)	3.2% 2/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	0.00% 0/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Gastrointestinal disorders Vomiting	4.8% 3/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	3.8% 2/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Nervous system disorders Neuropathy: motor	0.00% 0/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	1.9% 1/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Blood and lymphatic system disorders Neutrophils/granulocytes (ANC/AGC)	1.6% 1/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	7.7% 4/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Musculoskeletal and connective tissue disorders Musculoskeletal/Soft Tissue - Other (Specify, __)KNEE PAIN AND SWELLING	0.00% 0/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	1.9% 1/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Renal and urinary disorders Obstruction, GU: Ureter	0.00% 0/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	1.9% 1/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Gastrointestinal disorders Obstruction, GI: Colon	1.6% 1/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	0.00% 0/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Gastrointestinal disorders Pain: Abdomen NOS	1.6% 1/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	5.8% 3/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Musculoskeletal and connective tissue disorders Pain: Chest wall	1.6% 1/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	0.00% 0/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Gastrointestinal disorders Pain: Intestine	1.6% 1/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	0.00% 0/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Musculoskeletal and connective tissue disorders Pain: Joint	1.6% 1/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	0.00% 0/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Gastrointestinal disorders Nausea	1.6% 1/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	5.8% 3/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Nervous system disorders Neurology - Other (Specify, __)DECREASED RESPONSIVENESS AFTER SEDATION	1.6% 1/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	0.00% 0/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Nervous system disorders Neuropathy: sensory	1.6% 1/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	0.00% 0/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Gastrointestinal disorders Ascites (non-malignant)	1.6% 1/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	0.00% 0/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Metabolism and nutrition disorders Albumin, serum-low (hypoalbuminemia)	0.00% 0/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	1.9% 1/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Cardiac disorders Cardiac General - Other (Specify, __)SINUS BRADYCARDIA	0.00% 0/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	1.9% 1/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Cardiac disorders Cardiac ischemia/infarction	1.6% 1/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	0.00% 0/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Nervous system disorders CNS cerebrovascular ischemia	0.00% 0/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	1.9% 1/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
General disorders Death not associated with CTCAE term: Death NOS	4.8% 3/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	3.8% 2/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Death not associated with CTCAE term: Disease progression NOS	0.00% 0/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	5.8% 3/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Gastrointestinal disorders Dehydration	4.8% 3/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	5.8% 3/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Gastrointestinal disorders Diarrhea	4.8% 3/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	1.9% 1/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Gastrointestinal disorders Distension/bloating, abdominal	1.6% 1/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	0.00% 0/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Gastrointestinal disorders Dysphagia (difficulty swallowing)	1.6% 1/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	3.8% 2/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Respiratory, thoracic and mediastinal disorders Dyspnea (shortness of breath)	7.9% 5/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	1.9% 1/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Gastrointestinal disorders Esophagitis	1.6% 1/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	0.00% 0/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
General disorders Fatigue (asthenia, lethargy, malaise)	1.6% 1/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	5.8% 3/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Infections and infestations Febrile neutropenia	3.2% 2/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	1.9% 1/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
General disorders Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)	0.00% 0/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	5.8% 3/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Gastrointestinal disorders Gastrointestinal - Other (Specify, __)MALIGNANT ASCITES	0.00% 0/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	1.9% 1/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Gastrointestinal disorders Gastrointestinal - Other (Specify, __)GASTRIC PERFORATION	1.6% 1/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	0.00% 0/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Blood and lymphatic system disorders Hemoglobin	1.6% 1/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	0.00% 0/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Gastrointestinal disorders Hemorrhage, GI: Esophagus	1.6% 1/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	0.00% 0/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Gastrointestinal disorders Hemorrhage, GI: Stomach	1.6% 1/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	3.8% 2/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Gastrointestinal disorders Hemorrhage, GI: Lower GI NOS	1.6% 1/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	0.00% 0/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
General disorders Hemorrhage, GI: Upper GI NOS	4.8% 3/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	0.00% 0/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Hepatobiliary disorders Hepatobiliary/Pancreas - Other (Specify, __)VENO-OCCLUSIVE DISEASE	1.6% 1/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	0.00% 0/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Cardiac disorders Hypotension	1.6% 1/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	0.00% 0/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Infections and infestations Infection - Other (Specify, __)PLEURAL ABSCESS	1.6% 1/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	0.00% 0/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Infections and infestations Infection - Other (Specify, __)THRUSH	1.6% 1/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	0.00% 0/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Infections and infestations Infection with Grade 3 or 4 neutrophils: Lung (pneumonia)	1.6% 1/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	0.00% 0/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils: Catheter-related	1.6% 1/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	0.00% 0/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils: Kidney	1.6% 1/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	0.00% 0/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils: Lung (pneumonia)	3.2% 2/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	0.00% 0/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils: Wound	1.6% 1/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	0.00% 0/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Infections and infestations Infection with unknown ANC: Lung (pneumonia)	1.6% 1/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	0.00% 0/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Infections and infestations Infection with unknown ANC: Pleura (empyema)	1.6% 1/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	0.00% 0/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Blood and lymphatic system disorders Leukocytes (total WBC)	0.00% 0/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	3.8% 2/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Blood and lymphatic system disorders Lymphopenia	0.00% 0/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	1.9% 1/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Nervous system disorders Mental status	0.00% 0/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	1.9% 1/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Musculoskeletal and connective tissue disorders Muscle weakness, generalized or specific area (not due to neuropathy): Extremity-lower	0.00% 0/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	1.9% 1/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Musculoskeletal and connective tissue disorders Muscle weakness, generalized or specific area (not due to neuropathy): Extremity-upper	1.6% 1/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	0.00% 0/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.

Other adverse events

Measure	Arm I (FOLFOX Regimen and Placebo) n=63 participants at risk Patients receive FOLFOX chemotherapy comprising oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil bolus and then IV over 46-48 hours on day 1. Patients also receive placebo PO QD on days 1-14. Courses repeat every 2 weeks in the absence of unacceptable toxicity or disease progression.	Arm II (FOLFOX Regimen and Vismodegib) n=52 participants at risk Patients receive FOLFOX chemotherapy as in arm I. Patients also receive vismodegib PO on days 1-14. Courses repeat every 2 weeks in the absence of unacceptable toxicity or disease progression.
Metabolism and nutrition disorders Albumin, serum-low (hypoalbuminemia)	55.6% 35/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	40.4% 21/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Metabolism and nutrition disorders Alkaline phosphatase	34.9% 22/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	42.3% 22/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Immune system disorders Allergic reaction/hypersensitivity (including drug fever)	6.3% 4/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	3.8% 2/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Respiratory, thoracic and mediastinal disorders Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip)	0.00% 0/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	9.6% 5/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Metabolism and nutrition disorders ALT, SGPT (serum glutamic pyruvic transaminase)	17.5% 11/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	44.2% 23/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Gastrointestinal disorders Anorexia	42.9% 27/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	38.5% 20/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Gastrointestinal disorders Ascites (non-malignant)	4.8% 3/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	0.00% 0/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Metabolism and nutrition disorders AST, SGOT(serum glutamic oxaloacetic transaminase)	31.7% 20/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	44.2% 23/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Metabolism and nutrition disorders Bicarbonate, serum-low	3.2% 2/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	13.5% 7/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Metabolism and nutrition disorders Bilirubin (hyperbilirubinemia)	12.7% 8/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	7.7% 4/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Blood and lymphatic system disorders Blood/Bone Marrow - Other (Specify, __)LOW EOSINOPHILS	3.2% 2/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	0.00% 0/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Blood and lymphatic system disorders Blood/Bone Marrow - Other (Specify, __)HIGH LYMPHOCYTES	4.8% 3/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	0.00% 0/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Blood and lymphatic system disorders Blood/Bone Marrow - Other (Specify, __)MONOCYTOSIS	6.3% 4/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	3.8% 2/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Metabolism and nutrition disorders Calcium, serum-low (hypocalcemia)	30.2% 19/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	17.3% 9/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Skin and subcutaneous tissue disorders Cheilitis	3.2% 2/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	0.00% 0/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Gastrointestinal disorders Constipation	38.1% 24/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	42.3% 22/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Respiratory, thoracic and mediastinal disorders Cough	20.6% 13/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	17.3% 9/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Metabolism and nutrition disorders Creatinine	4.8% 3/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	7.7% 4/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Gastrointestinal disorders Dehydration	6.3% 4/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	11.5% 6/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Gastrointestinal disorders Diarrhea	50.8% 32/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	40.4% 21/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Gastrointestinal disorders Distension/bloating, abdominal	0.00% 0/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	9.6% 5/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Nervous system disorders Dizziness	20.6% 13/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	23.1% 12/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Gastrointestinal disorders Dry mouth/salivary gland (xerostomia)	4.8% 3/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	3.8% 2/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Skin and subcutaneous tissue disorders Dry skin	11.1% 7/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	5.8% 3/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Gastrointestinal disorders Dysphagia (difficulty swallowing)	17.5% 11/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	23.1% 12/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Respiratory, thoracic and mediastinal disorders Dyspnea (shortness of breath)	20.6% 13/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	15.4% 8/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Blood and lymphatic system disorders Edema:limb	14.3% 9/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	7.7% 4/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
General disorders Fatigue (asthenia, lethargy, malaise)	69.8% 44/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	84.6% 44/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
General disorders Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)	11.1% 7/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	9.6% 5/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Musculoskeletal and connective tissue disorders Fracture	0.00% 0/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	3.8% 2/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Gastrointestinal disorders Flatulence	3.2% 2/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	0.00% 0/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
General disorders Flu-like syndrome	4.8% 3/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	0.00% 0/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Gastrointestinal disorders Gastritis (including bile reflux gastritis)	3.2% 2/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	3.8% 2/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Metabolism and nutrition disorders Glucose, serum-high (hyperglycemia)	49.2% 31/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	42.3% 22/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Metabolism and nutrition disorders Glucose, serum-low (hypoglycemia)	4.8% 3/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	9.6% 5/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Skin and subcutaneous tissue disorders Hair loss/alopecia (scalp or body)	11.1% 7/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	17.3% 9/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Gastrointestinal disorders Heartburn/dyspepsia	6.3% 4/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	19.2% 10/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Blood and lymphatic system disorders Hemoglobin	58.7% 37/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	65.4% 34/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Blood and lymphatic system disorders Hemolysis (e.g., immune hemolytic anemia, drug-related hemolysis)	4.8% 3/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	3.8% 2/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Gastrointestinal disorders Hemorrhage, GI: Esophagus	0.00% 0/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	3.8% 2/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Gastrointestinal disorders Hemorrhage, GI: Rectum	3.2% 2/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	0.00% 0/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Respiratory, thoracic and mediastinal disorders Hemorrhage, pulmonary/upper respiratory: Nose	12.7% 8/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	9.6% 5/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Respiratory, thoracic and mediastinal disorders Hiccoughs (hiccups, singultus)	3.2% 2/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	0.00% 0/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Cardiac disorders Hypertension	6.3% 4/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	0.00% 0/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Cardiac disorders Hypotension	4.8% 3/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	0.00% 0/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Infections and infestations Infection - Other (Specify, __)THRUSH	6.3% 4/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	5.8% 3/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Infections and infestations Infection with normal ANC or Grade 1 or 2 neutrophils: External ear (otitis externa)	3.2% 2/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	0.00% 0/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Infections and infestations Infection with unknown ANC: Urinary tract NOS	0.00% 0/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	3.8% 2/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Investigations INR (International Normalized Ratio of prothrombin time)	0.00% 0/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	3.8% 2/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
General disorders Insomnia	7.9% 5/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	21.2% 11/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Blood and lymphatic system disorders Leukocytes (total WBC)	63.5% 40/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	55.8% 29/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Blood and lymphatic system disorders Lymphopenia	36.5% 23/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	30.8% 16/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Metabolism and nutrition disorders Magnesium, serum-low (hypomagnesemia)	0.00% 0/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	7.7% 4/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Nervous system disorders Memory impairment	3.2% 2/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	0.00% 0/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Metabolism and nutrition disorders Metabolic/Laboratory - Other (Specify, __)LOW CO2	3.2% 2/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	0.00% 0/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Metabolism and nutrition disorders Metabolic/Laboratory - Other (Specify, __)TOTAL PROTEIN DECREASED	6.3% 4/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	0.00% 0/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Nervous system disorders Mood alteration: Anxiety	6.3% 4/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	5.8% 3/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Nervous system disorders Mood alteration: Depression	6.3% 4/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	11.5% 6/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Gastrointestinal disorders Mucositis/stomatitis (clinical exam): Oral cavity	19.0% 12/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	13.5% 7/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Gastrointestinal disorders Mucositis/stomatitis (functional/symptomatic): Oral cavity	14.3% 9/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	7.7% 4/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Musculoskeletal and connective tissue disorders Muscle weakness, generalized or specific area (not due to neuropathy): Whole body/generalized	4.8% 3/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	0.00% 0/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Respiratory, thoracic and mediastinal disorders Nasal cavity/paranasal sinus reactions	3.2% 2/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	0.00% 0/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Gastrointestinal disorders Nausea	63.5% 40/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	78.8% 41/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Nervous system disorders Neurology - Other (Specify, __)COLD SENSITIVITY	7.9% 5/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	7.7% 4/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Nervous system disorders Neuropathy: motor	6.3% 4/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	5.8% 3/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Nervous system disorders Neuropathy: sensory	66.7% 42/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	80.8% 42/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Blood and lymphatic system disorders Neutrophils/granulocytes (ANC/AGC)	44.4% 28/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	63.5% 33/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Musculoskeletal and connective tissue disorders Pain - Other (Specify, __)GROIN	3.2% 2/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	0.00% 0/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Musculoskeletal and connective tissue disorders Pain - Other (Specify, __)RIB	3.2% 2/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	0.00% 0/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Gastrointestinal disorders Pain: Abdomen NOS	36.5% 23/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	7.7% 4/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Musculoskeletal and connective tissue disorders Pain: Back	14.3% 9/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	7.7% 4/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Musculoskeletal and connective tissue disorders Pain: Bone	3.2% 2/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	0.00% 0/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Musculoskeletal and connective tissue disorders Pain: Chest wall	4.8% 3/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	0.00% 0/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
General disorders Pain: Chest/thorax NOS	9.5% 6/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	7.7% 4/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Gastrointestinal disorders Pain: Esophagus	3.2% 2/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	0.00% 0/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Musculoskeletal and connective tissue disorders Pain: Extremity-limb	14.3% 9/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	13.5% 7/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Nervous system disorders Pain: Head/headache	9.5% 6/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	15.4% 8/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Musculoskeletal and connective tissue disorders Pain: Joint	9.5% 6/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	11.5% 6/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Musculoskeletal and connective tissue disorders Pain: Muscle	3.2% 2/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	3.8% 2/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Musculoskeletal and connective tissue disorders Pain: Neck	3.2% 2/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	9.6% 5/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Gastrointestinal disorders Pain: Oral cavity	9.5% 6/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	3.8% 2/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Gastrointestinal disorders Pain: Stomach	4.8% 3/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	3.8% 2/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Respiratory, thoracic and mediastinal disorders Pain: Throat/pharynx/larynx	9.5% 6/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	0.00% 0/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Cardiac disorders Palpitations	4.8% 3/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	0.00% 0/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Metabolism and nutrition disorders Phosphate, serum-low (hypophosphatemia)	7.9% 5/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	5.8% 3/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Skin and subcutaneous tissue disorders Photosensitivity	0.00% 0/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	3.8% 2/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Blood and lymphatic system disorders Platelets	57.1% 36/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	61.5% 32/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Metabolism and nutrition disorders Potassium, serum-high (hyperkalemia)	9.5% 6/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	0.00% 0/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Metabolism and nutrition disorders Potassium, serum-low (hypokalemia)	34.9% 22/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	23.1% 12/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Skin and subcutaneous tissue disorders Pruritus/itching	3.2% 2/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	3.8% 2/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Respiratory, thoracic and mediastinal disorders Pulmonary/Upper Respiratory - Other (Specify, __)RUNNY NOSE	3.2% 2/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	0.00% 0/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Skin and subcutaneous tissue disorders Rash/desquamation	9.5% 6/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	11.5% 6/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Skin and subcutaneous tissue disorders Rash: acne/acneiform	3.2% 2/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	3.8% 2/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Skin and subcutaneous tissue disorders Rash: hand-foot skin reaction	4.8% 3/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	7.7% 4/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
General disorders Rigors/chills	4.8% 3/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	11.5% 6/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Metabolism and nutrition disorders Sodium, serum-high (hypernatremia)	3.2% 2/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	0.00% 0/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Metabolism and nutrition disorders Sodium, serum-low (hyponatremia)	34.9% 22/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	32.7% 17/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Gastrointestinal disorders Taste alteration (dysgeusia)	15.9% 10/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	46.2% 24/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Vascular disorders Thrombosis/thrombus/embolism	0.00% 0/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	11.5% 6/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Nervous system disorders Tremor	0.00% 0/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	3.8% 2/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Renal and urinary disorders Urinary frequency/urgency	4.8% 3/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	5.8% 3/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Renal and urinary disorders Urinary retention (including neurogenic bladder)	4.8% 3/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	0.00% 0/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Eye disorders Vision-blurred vision	7.9% 5/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	3.8% 2/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Respiratory, thoracic and mediastinal disorders Voice changes/dysarthria (e.g., hoarseness, loss or alteration in voice, laryngitis)	3.2% 2/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	3.8% 2/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
Gastrointestinal disorders Vomiting	44.4% 28/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	42.3% 22/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.
General disorders Weight loss	30.2% 19/63 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.	28.8% 15/52 • Up to 4 years. All the adverse events above the reporting threshold are reported here regardless of attributions. Sixty three patients on the placebo arm and 52 on the Vismodegib arm started treatments; 1 and 8 patients did not receive treatments, respectively.

Additional Information

Deirdre Cohen, MD

Perlmutter Cancer Center at NYU Langone

Phone: 212-731-5656

Email: deirdre.cohen@nyumc.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: LTE60