Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Completed 18 and over NCI MDA-ID-02063 NCI-4772, NCT00055809, 4772

Objectives

1. Determine the progression-free survival rate in patients with metastatic or unresectable carcinoid tumors treated with bevacizumab and PEG-interferon alfa-2b.
2. Determine the tumor response rate (complete and partial) in patients treated with this regimen.
3. Determine the biochemical response rate of patients treated with this regimen.
4. Determine the qualitative and quantitative toxicity and reversibility of toxicity of this regimen in these patients.

Entry 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)

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

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/mm³
• Platelet count > 100,000/mm³
• 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 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

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

Expected Enrollment

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

Outcomes

Tumor response rate as measured by RECIST criteria after 18 weeks of treatment, and then after completion of study treatment

Progression free survival measured after treatment
Biochemical response rate measured after treatment
Safety as measured by CTC v3.0 criteria for adverse outcomes throughout the trial

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.

Yao JC, Phan A, Hoff PM, et al.: Targeting vascular endothelial growth factor in advanced carcinoid tumor: a random assignment phase II study of depot octreotide with bevacizumab and pegylated interferon alpha-2b. J Clin Oncol 26 (8): 1316-23, 2008.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

M. D. Anderson Cancer Center at University of Texas

James Yao, MD, Protocol chair		Ph: 713-792-2828; 800-392-1611

Registry Information
Official Title		Phase II Study Of Bevacizumab And PEG Interferon Alpha-2b (PEG Intron) In Patients With Metastatic, Or Unresectable Carcinoid Tumors
Trial Start Date		2003-01-22
Registered in ClinicalTrials.gov		NCT00055809
Date Submitted to PDQ		2003-01-13
Information Last Verified		2006-01-17
NCI Grant/Contract Number		CM17003, CA16672

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