Bevacizumab and Gemcitabine Combined With Either Cetuximab or Erlotinib in Treating Patients With Advanced Pancreatic Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00091026
First received: September 7, 2004
Last updated: April 28, 2014
Last verified: December 2012
  Purpose

This randomized phase II trial is studying bevacizumab, gemcitabine, and cetuximab to see how well they work compared to bevacizumab, gemcitabine, and erlotinib in treating patients with advanced pancreatic cancer. Monoclonal antibodies, such as cetuximab and bevacizumab, can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop tumor cells from dividing so they stop growing or die. Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Combining bevacizumab and gemcitabine with either cetuximab or erlotinib may kill more tumor cells.


Condition Intervention Phase
Adenocarcinoma of the Pancreas
Recurrent Pancreatic Cancer
Stage II Pancreatic Cancer
Stage III Pancreatic Cancer
Stage IV Pancreatic Cancer
Biological: cetuximab
Drug: gemcitabine hydrochloride
Biological: bevacizumab
Drug: erlotinib hydrochloride
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Phase II Study of Bevacizumab (NSC# 704865) and Gemcitabine in Combination With Either Cetuximab (NSC# 714692) or OSI-774 (NSC# 718781) in Patients With Advanced Pancreatic Cancer

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Objective Response Rate (Complete or Partial Response) Evaluated Using the Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression-free Survival [ Time Frame: 36 months ] [ Designated as safety issue: No ]
    Median progression-free survival time (time from randomization to disease progression or death from any cause). Analyzed using the Kaplan-Meier (1958) estimator and their associated 95% confidence intervals determined using the method described in Brookmeyer and Crowley.

  • Overall Survival [ Time Frame: 36 months ] [ Designated as safety issue: No ]
    Time from randomization until death from any cause. Analyzed using the Kaplan-Meier (1958) estimator and their associated 5% confidence intervals determined using the method described in Brookmeyer and Crowley.


Enrollment: 143
Study Start Date: July 2004
Study Completion Date: January 2011
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (cetuximab, gemcitabine hydrochloride, bevacizumab)
Patients receive cetuximab IV over 1-2 hours on days 1, 8, 15, and 22; gemcitabine IV over 30 minutes on days 1, 8, and 15; and bevacizumab IV over 30-90 minutes on days 1 and 15.
Biological: cetuximab
Given IV
Other Names:
  • C225
  • C225 monoclonal antibody
  • IMC-C225
  • MOAB C225
  • monoclonal antibody C225
Drug: gemcitabine hydrochloride
Given IV
Other Names:
  • dFdC
  • difluorodeoxycytidine hydrochloride
  • gemcitabine
  • Gemzar
Biological: bevacizumab
Given IV
Other Names:
  • anti-VEGF humanized monoclonal antibody
  • anti-VEGF monoclonal antibody
  • Avastin
  • rhuMAb VEGF
Experimental: Arm II (gemcitabine hydrochloride, bevacizumab, erlotinib)
Patients receive gemcitabine and bevacizumab as in arm I. Patients also receive oral erlotinib once daily on days 1-5, 8-12, and 15-26.
Drug: gemcitabine hydrochloride
Given IV
Other Names:
  • dFdC
  • difluorodeoxycytidine hydrochloride
  • gemcitabine
  • Gemzar
Biological: bevacizumab
Given IV
Other Names:
  • anti-VEGF humanized monoclonal antibody
  • anti-VEGF monoclonal antibody
  • Avastin
  • rhuMAb VEGF
Drug: erlotinib hydrochloride
Given orally
Other Names:
  • CP-358,774
  • erlotinib
  • OSI-774

Detailed Description:

OBJECTIVES:

I. Compare the objective response rate in patients with advanced adenocarcinoma of the pancreas treated with bevacizumab and gemcitabine with cetuximab vs erlotinib.

II. Compare the toxicity of these regimens in these patients. III. Compare median progression-free and overall survival of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center (University of Chicago vs other) and ECOG performance status (0-1 vs 2). Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients receive cetuximab IV over 1-2 hours on days 1, 8, 15, and 22; gemcitabine IV over 30 minutes on days 1, 8, and 15; and bevacizumab IV over 30-90 minutes on days 1 and 15.

Arm II: Patients receive gemcitabine and bevacizumab as in arm I. Patients also receive oral erlotinib once daily on days 1-5, 8-12, and 15-26.

In both arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 54-126 patients (27-63 per treatment arm) will be accrued for this study within 16 months.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically confirmed adenocarcinoma of the pancreas

    • Advanced disease

      • Patients with locally advanced disease must have disease that extends outside the boundaries of a standard radiation port
  • Not amenable to curative surgery or radiotherapy
  • Measurable disease

    • At least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan
    • Pleural effusions and ascites are not considered measurable lesions
  • No CNS disease, including primary brain tumors or brain metastasis
  • No tumor invasion into the duodenum
  • Performance status - ECOG 0-2
  • More than 3 months
  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • WBC ≥ 3,000/mm^3
  • No history of bleeding diatheses
  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • SGOT and SGPT ≤ 2.5 times ULN (5 times ULN if liver metastases are present)
  • INR ≤ 1.5 (≤ 3 for patients on warfarin)
  • No esophageal varices
  • Creatinine ≤ 1.5 mg/dL
  • Creatinine clearance ≥ 60 mL/min
  • Urine protein < 1+
  • 24-hour urine protein < 500 mg
  • No history of a recent cerebrovascular accident
  • No clinically significant cardiovascular disease
  • No uncontrolled hypertension
  • No New York Heart Association class II-IV congestive heart failure
  • No serious cardiac arrhythmia requiring medication
  • No peripheral vascular disease ≥ grade II
  • None of the following arterial thromboembolic events within the past 6 months:

    • Transient ischemic attack
    • Cerebrovascular accident
    • Unstable angina
    • Myocardial infarction
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for at least 3 months after study participation
  • HIV negative
  • No significant traumatic injury within the past 28 days
  • No gastrointestinal tract disease resulting in an inability to take oral medication
  • No allergic reactions to compounds similar to bevacizumab, cetuximab, or erlotinib (e.g., Chinese hamster ovary cell products or recombinant humanized antibodies)
  • No serious or non-healing wound, ulcer, or bone fracture
  • No active infection requiring antibiotics
  • No other active malignancy within the past 5 years except nonmelanoma skin cancer or carcinoma in situ of the cervix
  • No prior bevacizumab or cetuximab
  • No other prior vascular endothelial growth factor inhibitors
  • No prior gemcitabine
  • No prior cytotoxic chemotherapy for metastatic disease
  • At least 4 weeks since prior adjuvant chemotherapy (6 weeks for mitomycin or nitrosoureas)
  • At least 4 weeks since prior radiotherapy

    • Must have a site of measurable disease outside the radiation port
  • No prior surgical procedure affecting absorption
  • More than 28 days since prior major surgical procedure or open biopsy
  • More than 7 days since prior core biopsy
  • No concurrent major surgical procedures
  • No prior erlotinib
  • No other prior epidermal growth factor receptor inhibitors
  • At least 30 days since prior investigational drugs
  • More than 1 month since prior thrombolytic agents
  • Concurrent warfarin or low molecular weight heparin allowed provided the following criteria are met:

    • Currently therapeutic on a stable dose
    • INR target range ≤ 3
    • Patients undergo weekly INR testing
    • No evidence of active bleeding or pathological condition that carries high risk of bleeding (e.g., tumor invading adjacent organs or esophageal varices)
  • No concurrent chronic daily therapy with aspirin (> 325 mg/day) or nonsteroidal anti-inflammatory medications known to inhibit platelet function
  • No other concurrent antiplatelet medications
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • No other concurrent anticancer therapies or agents
  • No other concurrent investigational drugs
  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: NCT00091026

Locations
United States, Illinois
University of Chicago
Chicago, Illinois, United States, 60637
Sponsors and Collaborators
Investigators
Principal Investigator: Hedy Kindler University of Chicago
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00091026     History of Changes
Other Study ID Numbers: NCI-2012-02622, NCI-2012-02622, NCI-6580, UCCRC-13200A, CDR0000383145, 13200A, 6580, N01CM62204, N01CM62203, N01CM62201, U01CA099118, P30CA014599
Study First Received: September 7, 2004
Results First Received: August 6, 2013
Last Updated: April 28, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Adenocarcinoma
Pancreatic Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Antibodies
Antibodies, Monoclonal
Gemcitabine
Erlotinib
Bevacizumab
Cetuximab
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents

ClinicalTrials.gov processed this record on August 25, 2014