RATIONALE: 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.

PURPOSE: 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.

Condition	Treatment or Intervention	Phase
recurrent gastrointestinal carcinoid tumor metastatic gastrointestinal carcinoid tumor regional gastrointestinal carcinoid tumor	Drug: PEG-interferon alfa-2b  Drug: bevacizumab  Procedure: anti-cytokine therapy  Procedure: antiangiogenesis therapy  Procedure: antibody therapy  Procedure: biological response modifier therapy  Procedure: cytokine therapy  Procedure: growth factor antagonist therapy  Procedure: interferon therapy  Procedure: monoclonal antibody therapy	Phase II

OBJECTIVES:

• Determine the progression-free survival rate in patients with metastatic or unresectable carcinoid tumors treated with bevacizumab and PEG-interferon alfa-2b.
• Determine the tumor response rate (complete and partial) in patients treated with this regimen.
• Determine the biochemical response rate of patients treated with this regimen.
• 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.

• 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.

PROJECTED ACCRUAL: A total of 44 patients will be accrued for this study.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• 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)

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• Zubrod 0-2 OR
• Karnofsky 70-100%

Life expectancy

• At least 12 weeks

Hematopoietic

• 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

Hepatic

• 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)

Renal

• 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

Cardiovascular

• No clinically significant cardiovascular disease
• No prior myocardial infarction
• No uncontrolled hypertension
• No New York Heart Association grade II-IV congestive heart failure
• No serious cardiac arrhythmia requiring medication
• No unstable angina
• No grade II or greater peripheral vascular disease within the past year
• No history of stroke

Pulmonary

• No chronic pulmonary disease (e.g., chronic obstructive pulmonary disease)
• No documented pulmonary hypertension

Immunologic

• 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

Other

• 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 CONCURRENT THERAPY: Biologic therapy

• Prior immunotherapy allowed
• No prior interferon
• No concurrent immunotherapy

Chemotherapy

• At least 4 weeks since prior chemotherapy, including radiosensitizers
• No more than 1 prior chemotherapy regimen, including radiosensitizers
• No concurrent chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• 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

Surgery

• At least 4 weeks since prior major surgery or open biopsy (1 week for minor surgery) and recovered

Other

• 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

Texas
      University of Texas - MD Anderson Cancer Center, Houston,  Texas,  77030-4009,  United States; Recruiting

Study chairs or principal investigators

James Yao, MD,  Study Chair,  M.D. Anderson Cancer Center   

Study ID Numbers:  CDR0000271225; MDA-ID-02063; NCI-4772
Record last reviewed:  March 2004
Record first received:  March 6, 2003
ClinicalTrials.gov Identifier:  NCT00055809
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2004-11-05