Trial Outcomes & Findings for Combination of Bevacizumab, Pertuzumab, and Sandostatin for Adv. Neuroendocrine Cancers (NCT NCT01121939)

NCT ID: NCT01121939

Last Updated: 2016-02-05

Results Overview

The Percentage of Patients Who Experience an Objective Benefit From Treatment. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

43 participants

Primary outcome timeframe

18 months

Results posted on

2016-02-05

Participant Flow

Participant milestones

Participant milestones
Measure	All Patients Bevacizumab: 15 mg/kg IV Day 1. The first dose should be administered over 90 minutes. If no adverse reactions occur after the initial dose, the second dose should be administered over a minimum of 60 minutes. If no adverse reactions occur after the second dose, all subsequent doses should be administered over a minimum of 30 minutes. Bevacizumab will be infused prior to pertuzumab. Pertuzumab: 840 mg IV loading dose infused over 60 minutes. The loading dose is given on Cycle 1, Day 1 or as below. Subsequent doses of pertuzumab are 420 mg IV. If the patient tolerates the initial infusion over 60 minutes, the patient may receive subsequent infusions over 30 minutes. Sandostatin LAR® Depot: 30 mg will be given every 28 days by IM injection.
Overall Study STARTED	43
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	43

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Combination of Bevacizumab, Pertuzumab, and Sandostatin for Adv. Neuroendocrine Cancers

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Patients n=43 Participants Bevacizumab: 15 mg/kg IV Day 1. The first dose should be administered over 90 minutes. If no adverse reactions occur after the initial dose, the second dose should be administered over a minimum of 60 minutes. If no adverse reactions occur after the second dose, all subsequent doses should be administered over a minimum of 30 minutes. Bevacizumab will be infused prior to pertuzumab. Pertuzumab: 840 mg IV loading dose infused over 60 minutes. The loading dose is given on Cycle 1, Day 1 or as below. Subsequent doses of pertuzumab are 420 mg IV. If the patient tolerates the initial infusion over 60 minutes, the patient may receive subsequent infusions over 30 minutes. Sandostatin LAR® Depot: 30 mg will be given every 28 days by IM injection.
Age, Continuous	62 years n=5 Participants
Sex: Female, Male Female	21 Participants n=5 Participants
Sex: Female, Male Male	22 Participants n=5 Participants
Region of Enrollment United States	43 participants n=5 Participants

PRIMARY outcome

Timeframe: 18 months

Population: Includes all patients

Outcome measures

Outcome measures
Measure	Typical Carcinoid n=32 Participants Patients with typical carcinoid disease	Pancreatic Islet Cell n=11 Participants Patients with pancreatic islet cell disease	All Patients n=43 Participants All patients on study (treatment is same for all patients)
Objective Response Rate (ORR)	16 percentage of participants	18 percentage of participants	16 percentage of participants

SECONDARY outcome

Timeframe: 18 months

Population: All patients on study

To define the toxicity and safety of the combination of bevacizumab, pertuzumab and Sandostatin LAR® when used in patients with advanced low grade neuroendocrine cancer - defined by grade 3/4, treatment-related toxicity

Outcome measures

Outcome measures
Measure	Typical Carcinoid n=43 Participants Patients with typical carcinoid disease	Pancreatic Islet Cell Patients with pancreatic islet cell disease	All Patients All patients on study (treatment is same for all patients)
Define Toxicity and Safety Hypertension	11 participants	—	—
Define Toxicity and Safety Pain	5 participants	—	—
Define Toxicity and Safety Left ventricular systolic dysfunction	5 participants	—	—
Define Toxicity and Safety Diarrhea	3 participants	—	—
Define Toxicity and Safety Anemia	1 participants	—	—
Define Toxicity and Safety Leukopenia	1 participants	—	—

SECONDARY outcome

Timeframe: 18 months

Population: Includes all patients (patients in both the typical carcinoid and pancreatic islet cell groups received the same treatment)

The Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Worsening of Their Disease. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Outcome measures

Outcome measures
Measure	Typical Carcinoid n=32 Participants Patients with typical carcinoid disease	Pancreatic Islet Cell n=11 Participants Patients with pancreatic islet cell disease	All Patients All patients on study (treatment is same for all patients)
Progression-Free Survival (PFS)	11.96 months Interval 3.9 to 15.7	5.49 months Interval 1.1 to 6.5	—

SECONDARY outcome

Timeframe: 18 months

Population: Includes all patients (patients in both the typical carcinoid and pancreatic islet cell groups received the same treatment)

The Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death

Outcome measures

Outcome measures
Measure	Typical Carcinoid n=32 Participants Patients with typical carcinoid disease	Pancreatic Islet Cell n=11 Participants Patients with pancreatic islet cell disease	All Patients All patients on study (treatment is same for all patients)
Overall Survival (OS)	NA months Interval 22.4 to Median OS and upper bound of 95% confidence interval not reached (NR) at this time	26.4 months Interval 3.0 to Upper bound of 95% confidence interval not reached (NR) at this time	—

SECONDARY outcome

Timeframe: 18 months

Population: Includes all patients

The Percentage of Patients Who Experience an Objective Benefit From Treatment or Experience Stable Disease. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), Neither Sufficient Shrinkage to Qualify For PR, Nor Sufficient Increase to Qualify for Progressive Disease; Disease Control Rate = CR + PR + SD.

Outcome measures

Outcome measures
Measure	Typical Carcinoid n=32 Participants Patients with typical carcinoid disease	Pancreatic Islet Cell n=11 Participants Patients with pancreatic islet cell disease	All Patients n=43 Participants All patients on study (treatment is same for all patients)
Disease Control Rate	72 percentage of participants	91 percentage of participants	77 percentage of participants

Adverse Events

All Patients

Serious events: 6 serious events

Other events: 42 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	All Patients n=43 participants at risk Bevacizumab: 15 mg/kg IV Day 1. The first dose should be administered over 90 minutes. If no adverse reactions occur after the initial dose, the second dose should be administered over a minimum of 60 minutes. If no adverse reactions occur after the second dose, all subsequent doses should be administered over a minimum of 30 minutes. Bevacizumab will be infused prior to pertuzumab. Pertuzumab: 840 mg IV loading dose infused over 60 minutes. The loading dose is given on Cycle 1, Day 1 or as below. Subsequent doses of pertuzumab are 420 mg IV. If the patient tolerates the initial infusion over 60 minutes, the patient may receive subsequent infusions over 30 minutes. Sandostatin LAR® Depot: 30 mg will be given every 28 days by IM injection.
Gastrointestinal disorders Abdominal Pain	2.3% 1/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Renal and urinary disorders Acute Kidney Injury	2.3% 1/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Gastrointestinal disorders Colonic Obstruction	2.3% 1/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Investigations Creatinine Increased	2.3% 1/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Gastrointestinal disorders Diarrhea	2.3% 1/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Musculoskeletal and connective tissue disorders Flank Pain	2.3% 1/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Infections and infestations Kidney Infection	2.3% 1/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Gastrointestinal disorders Nausea	4.7% 2/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms Benign, Malignant And Unspecified (Incl Cysts And Polyps) - Other, Carcinoid Syndrome	2.3% 1/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Respiratory, thoracic and mediastinal disorders Respiratory Failure	2.3% 1/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Gastrointestinal disorders Vomiting	4.7% 2/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment

Other adverse events

Other adverse events
Measure	All Patients n=43 participants at risk Bevacizumab: 15 mg/kg IV Day 1. The first dose should be administered over 90 minutes. If no adverse reactions occur after the initial dose, the second dose should be administered over a minimum of 60 minutes. If no adverse reactions occur after the second dose, all subsequent doses should be administered over a minimum of 30 minutes. Bevacizumab will be infused prior to pertuzumab. Pertuzumab: 840 mg IV loading dose infused over 60 minutes. The loading dose is given on Cycle 1, Day 1 or as below. Subsequent doses of pertuzumab are 420 mg IV. If the patient tolerates the initial infusion over 60 minutes, the patient may receive subsequent infusions over 30 minutes. Sandostatin LAR® Depot: 30 mg will be given every 28 days by IM injection.
Gastrointestinal disorders Diarrhea	62.8% 27/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
General disorders Fatigue	62.8% 27/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Respiratory, thoracic and mediastinal disorders Epistaxis	41.9% 18/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Nervous system disorders Headache	41.9% 18/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Vascular disorders Hypertension	41.9% 18/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Gastrointestinal disorders Nausea	39.5% 17/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Renal and urinary disorders Proteinuria	37.2% 16/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Blood and lymphatic system disorders Anemia	30.2% 13/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Gastrointestinal disorders Vomiting	25.6% 11/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Nervous system disorders Dizziness	23.3% 10/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Skin and subcutaneous tissue disorders Rash	23.3% 10/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Metabolism and nutrition disorders Anorexia	20.9% 9/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Gastrointestinal disorders Abdominal Pain	18.6% 8/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Metabolism and nutrition disorders Hyperglycemia	18.6% 8/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Investigations Aspartate Aminotransferase Increased	16.3% 7/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Respiratory, thoracic and mediastinal disorders Dyspnea	16.3% 7/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Metabolism and nutrition disorders Hypokalemia	16.3% 7/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Gastrointestinal disorders Mucositis	16.3% 7/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Musculoskeletal and connective tissue disorders Pain In Extremity	16.3% 7/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Gastrointestinal disorders Constipation	14.0% 6/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Nervous system disorders Dysgeusia	14.0% 6/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
General disorders Edema Limbs	14.0% 6/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Skin and subcutaneous tissue disorders Pruritus	14.0% 6/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Investigations Weight Loss	14.0% 6/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Investigations Alkaline Phosphatase Increased	11.6% 5/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Musculoskeletal and connective tissue disorders Arthralgia	11.6% 5/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Investigations Creatinine Increased	11.6% 5/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Skin and subcutaneous tissue disorders Dry Skin	11.6% 5/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Psychiatric disorders Insomnia	11.6% 5/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Musculoskeletal and connective tissue disorders Myalgia	11.6% 5/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Respiratory, thoracic and mediastinal disorders Nasal Congestion	11.6% 5/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Investigations Platelet Count Decreased	11.6% 5/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Infections and infestations Sinusitis	11.6% 5/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Investigations Alanine Aminotransferase Increased	9.3% 4/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Gastrointestinal disorders Bloating	9.3% 4/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Respiratory, thoracic and mediastinal disorders Cough	9.3% 4/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Investigations Ejection Fraction Decreased	9.3% 4/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Gastrointestinal disorders Gastroesophageal Reflux Disease	9.3% 4/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Musculoskeletal and connective tissue disorders Musculoskeletal And Connective Tissue Disorders - Other, Body Ache	9.3% 4/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Skin and subcutaneous tissue disorders Rash Acneiform	9.3% 4/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Investigations White Blood Cell Decreased	9.3% 4/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Skin and subcutaneous tissue disorders Alopecia	7.0% 3/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Musculoskeletal and connective tissue disorders Back Pain	7.0% 3/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Investigations Blood Bilirubin Increased	7.0% 3/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Metabolism and nutrition disorders Dehydration	7.0% 3/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
General disorders Fever	7.0% 3/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Musculoskeletal and connective tissue disorders Flank Pain	7.0% 3/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Vascular disorders Flushing	7.0% 3/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Gastrointestinal disorders Gastrointestinal Disorders - Other, Stomatitis	7.0% 3/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Respiratory, thoracic and mediastinal disorders Hoarseness	7.0% 3/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Metabolism and nutrition disorders Hypoalbuminemia	7.0% 3/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Metabolism and nutrition disorders Hypocalcemia	7.0% 3/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Infections and infestations Infections And Infestations - Other, Unknown	7.0% 3/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Injury, poisoning and procedural complications Injury, Poisoning And Procedural Complications - Other, Abrasion	7.0% 3/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Investigations Investigations - Other, Blood Urea Nitrogen Increased	7.0% 3/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
General disorders Pain	7.0% 3/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Gastrointestinal disorders Rectal Hemorrhage	7.0% 3/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Gastrointestinal disorders Rectal Pain	7.0% 3/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Infections and infestations Skin Infection	7.0% 3/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Respiratory, thoracic and mediastinal disorders Sore Throat	7.0% 3/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Infections and infestations Upper Respiratory Infection	7.0% 3/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Infections and infestations Urinary Tract Infection	7.0% 3/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Eye disorders Watering Eyes	7.0% 3/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Respiratory, thoracic and mediastinal disorders Allergic Rhinitis	4.7% 2/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Psychiatric disorders Anxiety	4.7% 2/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Injury, poisoning and procedural complications Bruising	4.7% 2/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Skin and subcutaneous tissue disorders Bullous Dermatitis	4.7% 2/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Psychiatric disorders Depression	4.7% 2/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
General disorders Edema	4.7% 2/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Injury, poisoning and procedural complications Fracture	4.7% 2/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Cardiac disorders Heart Failure	4.7% 2/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Renal and urinary disorders Hematuria	4.7% 2/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Vascular disorders Hot Flashes	4.7% 2/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Metabolism and nutrition disorders Hyponatremia	4.7% 2/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
General disorders Injection Site Reaction	4.7% 2/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Investigations Investigations - Other, Blood Protein Decreased	4.7% 2/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Cardiac disorders Left Ventricular Systolic Dysfunction	4.7% 2/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Infections and infestations Nail Infection	4.7% 2/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Gastrointestinal disorders Oral Hemorrhage	4.7% 2/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Gastrointestinal disorders Oral Pain	4.7% 2/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Respiratory, thoracic and mediastinal disorders Respiratory, Thoracic And Mediastinal Disorders - Other, Nasal Dryness	4.7% 2/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Respiratory, thoracic and mediastinal disorders Respiratory, Thoracic And Mediastinal Disorders - Other, Runny Nose	4.7% 2/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Infections and infestations Rhinitis Infective	4.7% 2/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Skin and subcutaneous tissue disorders Skin And Subcutaneous Tissue Disorders - Other	4.7% 2/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Skin and subcutaneous tissue disorders Skin And Subcutaneous Tissue Disorders - Other, Cold Sores	4.7% 2/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Skin and subcutaneous tissue disorders Skin And Subcutaneous Tissue Disorders - Other, Nail Changes	4.7% 2/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Ear and labyrinth disorders Tinnitus	4.7% 2/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment
Injury, poisoning and procedural complications Wound Complication	4.7% 2/43 • 18 months Includes adverse events of all grades, regardless of their relationship to study treatment

Additional Information

John D Hainsworth, MD

Sarah Cannon Research Institute

Phone: 1-877-691-7274

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The sponsor can review/embargo results communications prior to public release for a period that is \>60 but =180 days from date submitted to sponsor, who may require changes to the communication in order to remove specifically identified confidential information (other than study data) and/or delay the proposed publication to enable the sponsor to seek patent protection for inventions. The PI may not publish its results until 18 mos. after the trial has been completed at all sites
Publication restrictions are in place

Restriction type: OTHER