Clinical trial NCT00055809: Bevacizumab and PEG-Interferon Alfa-2b in Treating Patients With Metastatic or Unresectable Carcinoid Tumors
Official title: Phase II Study Of Bevacizumab And PEG Interferon Alpha-2b (PEG Intron) In Patients With Metastatic, Or Unresectable Carcinoid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Gastrointestinal Carcinoid Tumor
Recurrent Gastrointestinal Carcinoid Tumor
Regional Gastrointestinal Carcinoid Tumor
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-03-07
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Tumor response rate (CR + PR) as measured by RECIST criteria
timeFrame: Up to 4 years
Secondary outcomes:
measure: Progression free survival
timeFrame: From the time of initial treatment to the time of PD or death, assessed up to 4 years
measure: Biochemical response rate measured after treatment
timeFrame: Up to 4 years
measure: Toxicity graded according to CTC v3.0 criteria for adverse outcomes
timeFrame: Up to 4 years
Other outcomes:
Locations:
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: James Yao
role: PRINCIPAL_INVESTIGATOR
References: