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

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ClinicalTrials.gov Identifier: NCT01121939
Recruitment Status : Completed
First Posted : May 12, 2010
Results First Posted : September 23, 2015
Last Update Posted : February 5, 2016
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
SCRI Development Innovations, LLC

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Neuroendocrine Carcinoma
Interventions Drug: Bevacizumab
Drug: Pertuzumab
Drug: Sandostatin LAR® Depot
Enrollment 43
Recruitment Details  
Pre-assignment Details  
Arm/Group Title All Patients
Hide Arm/Group Description

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.

Period Title: Overall Study
Started 43
Completed 0 [1]
Not Completed 43
[1]
Patients remained on-study until disease progression or unacceptable toxicity occurred.
Arm/Group Title All Patients
Hide Arm/Group Description

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 Number of Baseline Participants 43
Hide Baseline Analysis Population Description
All Patients
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 43 participants
62
(33 to 88)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 43 participants
Female
21
  48.8%
Male
22
  51.2%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 43 participants
43
1.Primary Outcome
Title Objective Response Rate (ORR)
Hide Description 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.
Time Frame 18 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Includes all patients
Arm/Group Title Typical Carcinoid Pancreatic Islet Cell All Patients
Hide Arm/Group Description:
Patients with typical carcinoid disease
Patients with pancreatic islet cell disease
All patients on study (treatment is same for all patients)
Overall Number of Participants Analyzed 32 11 43
Measure Type: Number
Unit of Measure: percentage of participants
16 18 16
2.Secondary Outcome
Title Define Toxicity and Safety
Hide Description 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
Time Frame 18 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All patients on study
Arm/Group Title All Patients
Hide Arm/Group Description:

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 Number of Participants Analyzed 43
Measure Type: Number
Unit of Measure: participants
Hypertension 11
Pain 5
Left ventricular systolic dysfunction 5
Diarrhea 3
Anemia 1
Leukopenia 1
3.Secondary Outcome
Title Progression-Free Survival (PFS)
Hide Description 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.
Time Frame 18 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Includes all patients (patients in both the typical carcinoid and pancreatic islet cell groups received the same treatment)
Arm/Group Title Typical Carcinoid Pancreatic Islet Cell
Hide Arm/Group Description:
Patients with typical carcinoid disease
Patients with pancreatic islet cell disease
Overall Number of Participants Analyzed 32 11
Median (95% Confidence Interval)
Unit of Measure: months
11.96
(3.9 to 15.7)
5.49
(1.1 to 6.5)
4.Secondary Outcome
Title Overall Survival (OS)
Hide Description The Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death
Time Frame 18 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Includes all patients (patients in both the typical carcinoid and pancreatic islet cell groups received the same treatment)
Arm/Group Title Typical Carcinoid Pancreatic Islet Cell
Hide Arm/Group Description:
Patients with typical carcinoid disease
Patients with pancreatic islet cell disease
Overall Number of Participants Analyzed 32 11
Median (95% Confidence Interval)
Unit of Measure: months
NA [1] 
(22.4 to NA)
26.4 [2] 
(3.0 to NA)
[1]
Median OS and upper bound of 95% confidence interval not reached (NR) at this time
[2]
Upper bound of 95% confidence interval not reached (NR) at this time
5.Secondary Outcome
Title Disease Control Rate
Hide Description 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.
Time Frame 18 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Includes all patients
Arm/Group Title Typical Carcinoid Pancreatic Islet Cell All Patients
Hide Arm/Group Description:
Patients with typical carcinoid disease
Patients with pancreatic islet cell disease
All patients on study (treatment is same for all patients)
Overall Number of Participants Analyzed 32 11 43
Measure Type: Number
Unit of Measure: percentage of participants
72 91 77
Time Frame 18 months
Adverse Event Reporting Description Includes adverse events of all grades, regardless of their relationship to study treatment
 
Arm/Group Title All Patients
Hide Arm/Group Description

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.

All-Cause Mortality
All Patients
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
All Patients
Affected / at Risk (%)
Total   6/43 (13.95%) 
Gastrointestinal disorders   
Abdominal Pain  1  1/43 (2.33%) 
Colonic Obstruction  1  1/43 (2.33%) 
Diarrhea  1  1/43 (2.33%) 
Nausea  1  2/43 (4.65%) 
Vomiting  1  2/43 (4.65%) 
Infections and infestations   
Kidney Infection  1  1/43 (2.33%) 
Investigations   
Creatinine Increased  1  1/43 (2.33%) 
Musculoskeletal and connective tissue disorders   
Flank Pain  1  1/43 (2.33%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Neoplasms Benign, Malignant And Unspecified (Incl Cysts And Polyps) - Other, Carcinoid Syndrome  1  1/43 (2.33%) 
Renal and urinary disorders   
Acute Kidney Injury  1  1/43 (2.33%) 
Respiratory, thoracic and mediastinal disorders   
Respiratory Failure  1  1/43 (2.33%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (4.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
All Patients
Affected / at Risk (%)
Total   42/43 (97.67%) 
Blood and lymphatic system disorders   
Anemia  1  13/43 (30.23%) 
Cardiac disorders   
Heart Failure  1  2/43 (4.65%) 
Left Ventricular Systolic Dysfunction  1  2/43 (4.65%) 
Ear and labyrinth disorders   
Tinnitus  1  2/43 (4.65%) 
Eye disorders   
Watering Eyes  1  3/43 (6.98%) 
Gastrointestinal disorders   
Diarrhea  1  27/43 (62.79%) 
Nausea  1  17/43 (39.53%) 
Vomiting  1  11/43 (25.58%) 
Abdominal Pain  1  8/43 (18.60%) 
Mucositis  1  7/43 (16.28%) 
Constipation  1  6/43 (13.95%) 
Bloating  1  4/43 (9.30%) 
Gastroesophageal Reflux Disease  1  4/43 (9.30%) 
Gastrointestinal Disorders - Other, Stomatitis  1  3/43 (6.98%) 
Rectal Hemorrhage  1  3/43 (6.98%) 
Rectal Pain  1  3/43 (6.98%) 
Oral Hemorrhage  1  2/43 (4.65%) 
Oral Pain  1  2/43 (4.65%) 
General disorders   
Fatigue  1  27/43 (62.79%) 
Edema Limbs  1  6/43 (13.95%) 
Fever  1  3/43 (6.98%) 
Pain  1  3/43 (6.98%) 
Edema  1  2/43 (4.65%) 
Injection Site Reaction  1  2/43 (4.65%) 
Infections and infestations   
Sinusitis  1  5/43 (11.63%) 
Infections And Infestations - Other, Unknown  1  3/43 (6.98%) 
Skin Infection  1  3/43 (6.98%) 
Upper Respiratory Infection  1  3/43 (6.98%) 
Urinary Tract Infection  1  3/43 (6.98%) 
Nail Infection  1  2/43 (4.65%) 
Rhinitis Infective  1  2/43 (4.65%) 
Injury, poisoning and procedural complications   
Injury, Poisoning And Procedural Complications - Other, Abrasion  1  3/43 (6.98%) 
Bruising  1  2/43 (4.65%) 
Fracture  1  2/43 (4.65%) 
Wound Complication  1  2/43 (4.65%) 
Investigations   
Aspartate Aminotransferase Increased  1  7/43 (16.28%) 
Weight Loss  1  6/43 (13.95%) 
Alkaline Phosphatase Increased  1  5/43 (11.63%) 
Creatinine Increased  1  5/43 (11.63%) 
Platelet Count Decreased  1  5/43 (11.63%) 
Alanine Aminotransferase Increased  1  4/43 (9.30%) 
Ejection Fraction Decreased  1  4/43 (9.30%) 
White Blood Cell Decreased  1  4/43 (9.30%) 
Blood Bilirubin Increased  1  3/43 (6.98%) 
Investigations - Other, Blood Urea Nitrogen Increased  1  3/43 (6.98%) 
Investigations - Other, Blood Protein Decreased  1  2/43 (4.65%) 
Metabolism and nutrition disorders   
Anorexia  1  9/43 (20.93%) 
Hyperglycemia  1  8/43 (18.60%) 
Hypokalemia  1  7/43 (16.28%) 
Dehydration  1  3/43 (6.98%) 
Hypoalbuminemia  1  3/43 (6.98%) 
Hypocalcemia  1  3/43 (6.98%) 
Hyponatremia  1  2/43 (4.65%) 
Musculoskeletal and connective tissue disorders   
Pain In Extremity  1  7/43 (16.28%) 
Arthralgia  1  5/43 (11.63%) 
Myalgia  1  5/43 (11.63%) 
Musculoskeletal And Connective Tissue Disorders - Other, Body Ache  1  4/43 (9.30%) 
Back Pain  1  3/43 (6.98%) 
Flank Pain  1  3/43 (6.98%) 
Nervous system disorders   
Headache  1  18/43 (41.86%) 
Dizziness  1  10/43 (23.26%) 
Dysgeusia  1  6/43 (13.95%) 
Psychiatric disorders   
Insomnia  1  5/43 (11.63%) 
Anxiety  1  2/43 (4.65%) 
Depression  1  2/43 (4.65%) 
Renal and urinary disorders   
Proteinuria  1  16/43 (37.21%) 
Hematuria  1  2/43 (4.65%) 
Respiratory, thoracic and mediastinal disorders   
Epistaxis  1  18/43 (41.86%) 
Dyspnea  1  7/43 (16.28%) 
Nasal Congestion  1  5/43 (11.63%) 
Cough  1  4/43 (9.30%) 
Hoarseness  1  3/43 (6.98%) 
Sore Throat  1  3/43 (6.98%) 
Allergic Rhinitis  1  2/43 (4.65%) 
Respiratory, Thoracic And Mediastinal Disorders - Other, Nasal Dryness  1  2/43 (4.65%) 
Respiratory, Thoracic And Mediastinal Disorders - Other, Runny Nose  1  2/43 (4.65%) 
Skin and subcutaneous tissue disorders   
Rash  1  10/43 (23.26%) 
Pruritus  1  6/43 (13.95%) 
Dry Skin  1  5/43 (11.63%) 
Rash Acneiform  1  4/43 (9.30%) 
Alopecia  1  3/43 (6.98%) 
Bullous Dermatitis  1  2/43 (4.65%) 
Skin And Subcutaneous Tissue Disorders - Other  1  2/43 (4.65%) 
Skin And Subcutaneous Tissue Disorders - Other, Cold Sores  1  2/43 (4.65%) 
Skin And Subcutaneous Tissue Disorders - Other, Nail Changes  1  2/43 (4.65%) 
Vascular disorders   
Hypertension  1  18/43 (41.86%) 
Flushing  1  3/43 (6.98%) 
Hot Flashes  1  2/43 (4.65%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (4.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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
Results Point of Contact
Name/Title: John D Hainsworth, MD
Organization: Sarah Cannon Research Institute
Phone: 1-877-691-7274
Responsible Party: SCRI Development Innovations, LLC
ClinicalTrials.gov Identifier: NCT01121939     History of Changes
Other Study ID Numbers: SCRI GI 135
First Submitted: May 10, 2010
First Posted: May 12, 2010
Results First Submitted: February 26, 2015
Results First Posted: September 23, 2015
Last Update Posted: February 5, 2016