Trial Outcomes & Findings for Everolimus and Letrozole in Treating Patients With Recurrent Hormone Receptor Positive Ovarian, Fallopian Tube, or Primary Peritoneal Cavity Cancer (NCT NCT02283658)

NCT ID: NCT02283658

Last Updated: 2020-10-23

Results Overview

The percentage of PFS12 successes will be estimated by the number of successes divided by the total number of evaluable patients. Ninety-five percent confidence intervals for the true success proportion will be calculated according to the exact binomial method. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), Disease progression in evaluable patients will be defined as one or more of the following: * Any new disease and/or clear progression of evaluable disease; OR * 2 fold elevation in CA-125 from its lowest level (either initial level or nadir, whichever is lowest, since study enrollment) combined with CA-125 elevation confirmed by re-assay at any time.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 20 participants
• Primary outcome timeframe: 12 weeks
• Results posted on: 2020-10-23

Participant Flow

Participant milestones

Measure	Treatment (Everolimus and Letrozole) Patients receive everolimus PO QD and letrozole PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Overall Study STARTED	20
Overall Study COMPLETED	19
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Measure	Treatment (Everolimus and Letrozole) Patients receive everolimus PO QD and letrozole PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Overall Study Withdrawal by Subject	1

Baseline Characteristics

Everolimus and Letrozole in Treating Patients With Recurrent Hormone Receptor Positive Ovarian, Fallopian Tube, or Primary Peritoneal Cavity Cancer

Baseline characteristics by cohort

Measure	Treatment (Everolimus and Letrozole) n=19 Participants Patients receive everolimus PO QD and letrozole PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Age, Continuous	60.0 years n=5 Participants
Sex: Female, Male Female	19 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	19 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: 12 weeks

Population: All evaluable patients

The percentage of PFS12 successes will be estimated by the number of successes divided by the total number of evaluable patients. Ninety-five percent confidence intervals for the true success proportion will be calculated according to the exact binomial method. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), Disease progression in evaluable patients will be defined as one or more of the following:

• Any new disease and/or clear progression of evaluable disease; OR
• 2 fold elevation in CA-125 from its lowest level (either initial level or nadir, whichever is lowest, since study enrollment) combined with CA-125 elevation confirmed by re-assay at any time.

Outcome measures

Measure	Treatment (Everolimus and Letrozole) n=19 Participants Patients receive everolimus PO QD and letrozole PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Percentage of Patients Alive and Progression Free Survival at 12 Weeks	47 percentage of patients Interval 24.0 to 71.0

SECONDARY outcome

Timeframe: Up to 2 years

Population: All evaluable patients

CA-125 response: The key secondary endpoint of the study will be a CA-125 response, defined as a 50% or greater reduction in baseline CA-125. The null hypothesis will be set at CA-125 response rate of 8.3%, based on the response of single agent letrozole, as reported by Bowman et al (7). The treatment of letrozole and everolimus will be considered promising, based on CA-125, if the observed CA-125 response rate is 30% or more.

Outcome measures

Measure	Treatment (Everolimus and Letrozole) n=19 Participants Patients receive everolimus PO QD and letrozole PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Percentage of Participants With CA-125 Response	21 percentage of patients Interval 6.0 to 46.0

SECONDARY outcome

Timeframe: Up to 24 weeks

Population: All evaluable patients

A confirmed tumor response is defined to be either a complete response or partial response noted as the objective status on 2 consecutive evaluations at least 4 weeks apart. A complete response (CR) in evaluable patients will be defined as:

• Disappearance of any sign of (evaluable) disease, AND
• Normalization of CA-125; if CA-125 normalizes, it should be confirmed at any time.

A partial response (PR) in evaluable patients will be defined as:

• Decrement in CA-125 by >50%, and
• Improvement in any additional evaluable disease (if present) as assessed by the enrolling physician.

Outcome measures

Measure	Treatment (Everolimus and Letrozole) n=19 Participants Patients receive everolimus PO QD and letrozole PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Confirmed Response Rate, Estimated Using RECIST 1.1 Criteria	16 percentage of patients Interval 3.0 to 40.0

SECONDARY outcome

Timeframe: Up to 30 days post-treatment

Population: All evaluable patients

The number of patients with adverse events.The maximum grade for each type of adverse event (AE) will be recorded for each patient, and frequency tables will be reviewed to determine AE patterns. These tables are reported in the adverse events section of this report.

Outcome measures

Measure	Treatment (Everolimus and Letrozole) n=19 Participants Patients receive everolimus PO QD and letrozole PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Number of Participants Experiencing Adverse Events	19 Participants

SECONDARY outcome

Timeframe: Time from registration to death from any cause, assessed up to 2 years

Population: All evaluable patients

OS will be estimated using the method of Kaplan-Meier.

Outcome measures

Measure	Treatment (Everolimus and Letrozole) n=19 Participants Patients receive everolimus PO QD and letrozole PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Overall Suravival(OS)	13 Months Interval 8.8 to Not Reached;Median was not reached due to too few PFS events.

SECONDARY outcome

Timeframe: Time from registration to the first of either disease progression or death from any cause, assessed up to 2 years

Population: All evaluable patients

PFS will be estimated using the method of Kaplan-Meier. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), Disease progression in evaluable patients will be defined as one or more of the following:

Any new disease and/or clear progression of evaluable disease; OR 2 fold elevation in CA-125 from its lowest level (either initial level or nadir, whichever is lowest, since study enrollment) combined with CA-125 elevation confirmed by re-assay at any time.

Outcome measures

Measure	Treatment (Everolimus and Letrozole) n=19 Participants Patients receive everolimus PO QD and letrozole PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Progression Free Survival (PFS)	3.9 Months Interval 2.8 to 11.0

OTHER_PRE_SPECIFIED outcome

Timeframe: 28 days following treatment initiation

The Fisher's Exact test will be used to measure the associations.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 28 days following treatment initiation

Will determine if response rates to letrozole and everolimus in PDX avatars correlate to responses noted in the patients. The Fisher's Exact test will be used to measure the associations.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 28 days following treatment initiation

"Response" will be defined as tumors with at least a 50% reduction in tumor volume at study end. "Unresponsive" will be defined as tumors with less than 10% tumor volume reduction at study end. Intermediate values will be defined as "Stable". Tumor growth curves will be plotted graphically and notated to indicate the outcome status of the originating patients. End of study tumor volumes will be correlated with outcome status of the originating patient as well. The Fisher's Exact test will be used to measure the associations.

Outcome measures

Outcome data not reported

Adverse Events

Treatment (Everolimus and Letrozole)

Serious events: 10 serious events

Other events: 19 other events

Deaths: 1 deaths

Serious adverse events

Measure	Treatment (Everolimus and Letrozole) n=19 participants at risk Patients receive everolimus PO QD and letrozole PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Blood and lymphatic system disorders Anemia	15.8% 3/19 • Number of events 4 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
Gastrointestinal disorders Abdominal pain	10.5% 2/19 • Number of events 3 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
Gastrointestinal disorders Colonic obstruction	5.3% 1/19 • Number of events 1 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
Gastrointestinal disorders Constipation	5.3% 1/19 • Number of events 1 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
Gastrointestinal disorders Diarrhea	5.3% 1/19 • Number of events 1 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
Gastrointestinal disorders Ileus	5.3% 1/19 • Number of events 1 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
Gastrointestinal disorders Nausea	15.8% 3/19 • Number of events 3 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
Gastrointestinal disorders Small intestinal obstruction	15.8% 3/19 • Number of events 4 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
Gastrointestinal disorders Vomiting	15.8% 3/19 • Number of events 3 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
General disorders Death NOS	5.3% 1/19 • Number of events 1 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
General disorders Edema limbs	5.3% 1/19 • Number of events 1 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
General disorders Fatigue	5.3% 1/19 • Number of events 1 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
General disorders Fever	5.3% 1/19 • Number of events 1 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
General disorders Pain	5.3% 1/19 • Number of events 1 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
Infections and infestations Infections and infestations - Other, specify	5.3% 1/19 • Number of events 1 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
Infections and infestations Skin infection	5.3% 1/19 • Number of events 1 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
Investigations Creatinine increased	5.3% 1/19 • Number of events 1 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
Investigations Neutrophil count decreased	10.5% 2/19 • Number of events 2 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
Investigations White blood cell decreased	10.5% 2/19 • Number of events 2 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumor pain	5.3% 1/19 • Number of events 1 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.

Other adverse events

Measure	Treatment (Everolimus and Letrozole) n=19 participants at risk Patients receive everolimus PO QD and letrozole PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Blood and lymphatic system disorders Anemia	36.8% 7/19 • Number of events 37 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
Gastrointestinal disorders Abdominal pain	15.8% 3/19 • Number of events 5 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
Gastrointestinal disorders Ascites	5.3% 1/19 • Number of events 1 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
Gastrointestinal disorders Bloating	10.5% 2/19 • Number of events 2 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
Gastrointestinal disorders Constipation	10.5% 2/19 • Number of events 2 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
Gastrointestinal disorders Diarrhea	63.2% 12/19 • Number of events 28 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
Gastrointestinal disorders Esophageal ulcer	5.3% 1/19 • Number of events 2 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
Gastrointestinal disorders Fecal incontinence	5.3% 1/19 • Number of events 1 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
Gastrointestinal disorders Gastroesophageal reflux disease	5.3% 1/19 • Number of events 1 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
Gastrointestinal disorders Gastrointestinal disorders - Other, specify	10.5% 2/19 • Number of events 2 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
Gastrointestinal disorders Mucositis oral	73.7% 14/19 • Number of events 36 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
Gastrointestinal disorders Nausea	42.1% 8/19 • Number of events 17 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
Gastrointestinal disorders Rectal pain	5.3% 1/19 • Number of events 1 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
Gastrointestinal disorders Vomiting	15.8% 3/19 • Number of events 3 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
General disorders Chills	5.3% 1/19 • Number of events 13 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
General disorders Edema limbs	10.5% 2/19 • Number of events 3 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
General disorders Fatigue	100.0% 19/19 • Number of events 89 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
General disorders Fever	5.3% 1/19 • Number of events 12 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
Investigations Alanine aminotransferase increased	10.5% 2/19 • Number of events 11 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
Investigations Alkaline phosphatase increased	15.8% 3/19 • Number of events 4 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
Investigations Aspartate aminotransferase increased	21.1% 4/19 • Number of events 11 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
Investigations Cholesterol high	15.8% 3/19 • Number of events 23 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
Investigations Neutrophil count decreased	26.3% 5/19 • Number of events 14 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
Investigations Platelet count decreased	31.6% 6/19 • Number of events 28 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
Investigations Urine output decreased	5.3% 1/19 • Number of events 1 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
Investigations White blood cell decreased	21.1% 4/19 • Number of events 21 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
Metabolism and nutrition disorders Anorexia	31.6% 6/19 • Number of events 28 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
Metabolism and nutrition disorders Dehydration	5.3% 1/19 • Number of events 1 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
Metabolism and nutrition disorders Hyperglycemia	5.3% 1/19 • Number of events 2 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
Metabolism and nutrition disorders Hyperkalemia	5.3% 1/19 • Number of events 1 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
Metabolism and nutrition disorders Hypertriglyceridemia	21.1% 4/19 • Number of events 23 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
Metabolism and nutrition disorders Hypoalbuminemia	5.3% 1/19 • Number of events 1 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
Metabolism and nutrition disorders Hypophosphatemia	5.3% 1/19 • Number of events 1 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
Musculoskeletal and connective tissue disorders Arthralgia	47.4% 9/19 • Number of events 41 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
Musculoskeletal and connective tissue disorders Back pain	5.3% 1/19 • Number of events 1 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
Nervous system disorders Dizziness	10.5% 2/19 • Number of events 3 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
Nervous system disorders Dysgeusia	5.3% 1/19 • Number of events 4 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
Nervous system disorders Headache	5.3% 1/19 • Number of events 1 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
Nervous system disorders Peripheral sensory neuropathy	5.3% 1/19 • Number of events 1 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
Nervous system disorders Tremor	5.3% 1/19 • Number of events 1 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
Psychiatric disorders Insomnia	5.3% 1/19 • Number of events 4 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
Renal and urinary disorders Hematuria	5.3% 1/19 • Number of events 1 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
Renal and urinary disorders Urinary frequency	5.3% 1/19 • Number of events 1 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
Reproductive system and breast disorders Pelvic pain	5.3% 1/19 • Number of events 1 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
Respiratory, thoracic and mediastinal disorders Epistaxis	5.3% 1/19 • Number of events 3 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
Respiratory, thoracic and mediastinal disorders Pneumonitis	5.3% 1/19 • Number of events 3 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
Skin and subcutaneous tissue disorders Alopecia	5.3% 1/19 • Number of events 4 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
Skin and subcutaneous tissue disorders Nail loss	5.3% 1/19 • Number of events 8 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
Skin and subcutaneous tissue disorders Pruritus	5.3% 1/19 • Number of events 2 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
Skin and subcutaneous tissue disorders Rash acneiform	36.8% 7/19 • Number of events 13 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
Skin and subcutaneous tissue disorders Rash maculo-papular	31.6% 6/19 • Number of events 12 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, specify	5.3% 1/19 • Number of events 1 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
Vascular disorders Hot flashes	15.8% 3/19 • Number of events 3 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.
Vascular disorders Hypertension	5.3% 1/19 • Number of events 1 • 2 years The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. All appropriate treatment areas should have access to a copy of the CTCAE version 4.0.

Additional Information

Gerardo Colon-Otero, M.D.

Mayo Clinic

Phone: (904) 953-2000

Email: gcolonotero@mayo.edu

Results disclosure agreements

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