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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00055809
First received: March 6, 2003
Last updated: January 22, 2013
Last verified: January 2013
  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. 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


Condition Intervention Phase
Metastatic Gastrointestinal Carcinoid Tumor
Recurrent Gastrointestinal Carcinoid Tumor
Regional Gastrointestinal Carcinoid Tumor
Biological: PEG-interferon alfa-2b
Biological: bevacizumab
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study Of Bevacizumab And PEG Interferon Alpha-2b (PEG Intron) In Patients With Metastatic, Or Unresectable Carcinoid Tumors

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Tumor response rate (CR + PR) as measured by RECIST criteria [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression free survival [ Time Frame: From the time of initial treatment to the time of PD or death, assessed up to 4 years ] [ Designated as safety issue: No ]
  • Biochemical response rate measured after treatment [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
  • Toxicity graded according to CTC v3.0 criteria for adverse outcomes [ Time Frame: Up to 4 years ] [ Designated as safety issue: Yes ]

Enrollment: 44
Study Start Date: January 2003
Primary Completion Date: June 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (bevacizumab)
Patients receive bevacizumab IV on day 1.
Biological: bevacizumab
Given IV
Other Names:
  • anti-VEGF humanized monoclonal antibody
  • anti-VEGF monoclonal antibody
  • Avastin
  • rhuMAb VEGF
Other: laboratory biomarker analysis
Optional correlative studies
Experimental: Arm II (PEG-interferon alfa-2b)
Patients receive PEG-interferon alfa-2b SC on days 1, 8, and 15.
Biological: PEG-interferon alfa-2b
Given SC
Other Names:
  • PEG-IFN alfa-2b
  • pegylated interferon alfa-2b
  • polyethylene glycol IFN-A2b
Other: laboratory biomarker analysis
Optional correlative studies

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00055809

Locations
United States, Texas
M D Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Investigators
Principal Investigator: James Yao M.D. Anderson Cancer Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00055809     History of Changes
Other Study ID Numbers: NCI-2012-02519, MDA-ID-02063, N01CM62202, CDR0000271225
Study First Received: March 6, 2003
Last Updated: January 22, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoid Tumor
Malignant Carcinoid Syndrome
Gastrointestinal Neoplasms
Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Bevacizumab
Interferons
Antibodies
Antibodies, Monoclonal
Interferon-alpha
Peginterferon alfa-2b
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 22, 2014