Bevacizumab and PEG-Interferon Alfa-2b in Treating Patients With Metastatic or Unresectable Carcinoid Tumors

Study Overview
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Brief Summary
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This randomized phase II trial is to see if combining bevacizumab with PEG-interferon alfa-2b works in treating patients who have metastatic or unresectable carcinoid tumors. Monoclonal antibodies, such as bevacizumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or deliver cancer-killing substances to them. PEG-interferon alfa-2b may stop the growth of cancer by stopping blood flow to the tumor. Combining bevacizumab with PEG-interferon alfa-2b may kill more cancer cells

Detailed Description
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OBJECTIVES: I. Determine the progression-free survival rate in patients with metastatic or unresectable carcinoid tumors treated with bevacizumab and PEG-interferon alfa-2b. II. Determine the tumor response rate (complete and partial) in patients treated with this regimen. III. Determine the biochemical response rate of patients treated with this regimen. IV. Determine the qualitative and quantitative toxicity and reversibility of toxicity of this regimen in these patients. OUTLINE: This is a randomized study. Patients are treated in 2 stages. Stage I: Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive bevacizumab IV on day 1. Arm II: Patients receive PEG-interferon alfa-2b subcutaneously (SC) on days 1, 8, and 15. In both arms, courses repeat every 3 weeks. Patients with progressive disease at 9 weeks proceed to stage II. All other patients proceed to stage II after 18 weeks on stage I. Stage II: Patients receive bevacizumab IV on day 1 and PEG-interferon alfa-2b SC once weekly. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients who achieve a complete response (CR) and remain in CR for 2 additional courses come off study. Patients are followed for survival.

Official Title
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Phase II Study Of Bevacizumab And PEG Interferon Alpha-2b (PEG Intron) In Patients With Metastatic, Or Unresectable Carcinoid Tumors

Conditions
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Metastatic Gastrointestinal Carcinoid Tumor, Recurrent Gastrointestinal Carcinoid Tumor, Regional Gastrointestinal Carcinoid Tumor

Intervention / Treatment
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* Biological: PEG-interferon alfa-2b
* Biological: bevacizumab
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed carcinoid tumor Metastatic or unresectable local-regional disease Measurable disease No osseous metastasis as the only site of disease No history or clinical evidence of CNS disease (e.g., primary brain tumor or any brain metastasis) Performance status - Zubrod 0-2 Performance status - Karnofsky 70-100% At least 12 weeks See Immunologic Absolute granulocyte count > 1,500/mm^3 Platelet count > 100,000/mm^3 Hemoglobin > 8 g/dL No bleeding diathesis or coagulopathy No hemoglobinopathies (e.g., thalassemia) or any other cause of hemolytic anemia Bilirubin < 1.5 mg/dL INR < 1.5 (if receiving warfarin) No evidence of decompensated liver disease (e.g., ascites, bleeding varices, or spontaneous encephalopathy) Creatinine < 1.5 mg/dL No baseline proteinuria Patients with proteinuria (≥ 2+ or ≥ 100 mg/dL on urinalysis) are allowed provided 24-hour urinary protein is < 500 mg No New York Heart Association grade II-IV congestive heart failure No serious cardiac arrhythmia requiring medication No clinically significant peripheral vascular disease No history of stroke None of the following within the past 6 months: Uncontrolled hypertension Transient ischemic attack Cerebrovascular accident Unstable angina Myocardial infarction No chronic pulmonary disease (e.g., chronic obstructive pulmonary disease) No documented pulmonary hypertension None of the following immunologically mediated diseases: Inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis) Rheumatoid arthritis Idiopathic thrombocytopenia purpura Systemic lupus erythematosus Autoimmune hemolytic anemia Scleroderma Severe psoriasis No serious concurrent infections No active infection requiring parental antibiotics on day 0 No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies No known hypersensitivity to interferon alfa or to any excipient or vehicle included in its formulation or delivery system Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No significant traumatic injury within the past 4 weeks No preexisting thyroid abnormality for which thyroid function can not be normalized by medication No concurrent nonmalignant uncontrolled medical illness or one whose control may be jeopardized by the complications of this study therapy No uncontrolled psychiatric disorder No psychiatric disorders that would preclude study compliance No other malignancy within the past 5 years except nonmelanoma skin cancer or carcinoma in situ of the cervix No serious nonhealing wound ulcer or bone fracture No seizures not controlled with standard medical therapy Prior immunotherapy allowed No prior interferon No concurrent immunotherapy At least 4 weeks since prior chemotherapy, including radiosensitizers No more than 1 prior chemotherapy regimen, including radiosensitizers No concurrent chemotherapy At least 4 weeks since prior radiotherapy Prior radiotherapy must not have contained the single evaluable lesion of this study in a radiation field No concurrent radiotherapy At least 4 weeks since prior major surgery or open biopsy (1 week for minor surgery) and recovered No concurrent or recent full-dose anticoagulants or thrombolytic agents (except as required to maintain patency of preexisting, permanent indwelling IV catheters) No concurrent chronic daily aspirin (more than 325 mg/day) or nonsteroidal anti-inflammatory medications known to inhibit platelet function

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (bevacizumab)<br>Patients receive bevacizumab IV on day 1. | Biological: bevacizumab<br>* Given IV<br>* Other names: rhuMAb VEGF;Other: laboratory biomarker analysis<br>* Optional correlative studies<br>|
| Experimental: Arm II (PEG-interferon alfa-2b)<br>Patients receive PEG-interferon alfa-2b SC on days 1, 8, and 15. | Biological: PEG-interferon alfa-2b<br>* Given SC<br>* Other names: polyethylene glycol IFN-A2b;Other: laboratory biomarker analysis<br>* Optional correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor response rate (CR + PR) as measured by RECIST criteria |  | Up to 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival |  | From the time of initial treatment to the time of PD or death, assessed up to 4 years | 
| Biochemical response rate measured after treatment |  | Up to 4 years | 
| Toxicity graded according to CTC v3.0 criteria for adverse outcomes |  | Up to 4 years |