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Cetuximab and Bevacizumab With or Without Gemcitabine to Treat Pancreatic Cancer
This study has been terminated.
( Due to lack of efficacy in both study arms. )
First Received: May 15, 2006   Last Updated: August 6, 2009   History of Changes
Sponsored by: ImClone LLC
Information provided by: ImClone LLC
ClinicalTrials.gov Identifier: NCT00326911
  Purpose

Eligible patients with pancreatic cancer will be treated with dual agent monoclonal antibody consisting of cetuximab and bevacizumab alone or in combination with gemcitabine


Condition Intervention Phase
Pancreatic Cancer
Biological: Cetuximab
Biological: Bevacizumab
Drug: Gemcitabine
Phase II

Study Type: Interventional
Study Design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study
Official Title: A Phase II, Randomized, Open-Label Study of Cetuximab and Bevacizumab Alone or in Combination With Fixed-Dose Rate Gemcitabine as First-Line Therapy of Patients With Metastatic Adenocarcinoma of the Pancreas

Resource links provided by NLM:


Further study details as provided by ImClone LLC:

Primary Outcome Measures:
  • Progression-free survival of patients with stage IV adenocarcinoma of the pancreas treated with either dual monoclonal antibody therapy consisting of cetuximab and bevacizumab or cetuximab and bevacizumab in combination with gemcitabine chemotherapy. [ Time Frame: Tumor response and progression ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Overall survival (OS) [ Time Frame: Patients will receive this regimen on 4-week cycles in the absence of PD or other withdrawal criteria. ] [ Designated as safety issue: No ]
  • Response rate in the subset of patients with measurable disease by RECIST [ Time Frame: Patients will receive this regimen on 4-week cycles in the absence of PD or other withdrawal criteria. ] [ Designated as safety issue: No ]
  • CA19-9 response rate in the subset of patients with elevated baseline values [ Time Frame: Patients will receive this regimen on 4-week cycles in the absence of PD or other withdrawal criteria. ] [ Designated as safety issue: No ]
  • Time to progression [ Time Frame: Patients will receive this regimen on 4-week cycles in the absence of PD or other withdrawal criteria. ] [ Designated as safety issue: No ]
  • Safety and tolerability [ Time Frame: Patients will receive this regimen on 4-week cycles in the absence of PD or other withdrawal criteria. ] [ Designated as safety issue: Yes ]
  • Quality of Life and pain control assessments [ Time Frame: Patients will receive this regimen on 4-week cycles in the absence of PD or other withdrawal criteria. ] [ Designated as safety issue: No ]
  • Evaluation of pharmacodynamic parameters, including analysis of tumor tissue, if available, for EGFR expression and for exploratory markers of tumor progression or response to therapy [ Time Frame: Patients will receive this regimen on 4-week cycles in the absence of PD or other withdrawal criteria. ] [ Designated as safety issue: No ]

Enrollment: 61
Study Start Date: May 2006
Study Completion Date: December 2008
Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
CBG: Active Comparator
Cetuximab 400 mg/m2 weekly (over 120 minutes) on day 1 of cycle 1 with subsequent weekly infusions of 250 mg/m2 (over 60 minutes), followed by bevacizumab 10 mg/kg (over 60 minutes) on day 1 and repeated every 2 weeks, and gemcitabine 1000 mg/m2/minute over 100 minutes weekly x 3 of 4 weeks. Both medications will be administered by intravenous infusion on the same day. The order of study drug administration will be cetuximab,bevacizumab, and gemcitabine . On day 1 of cycle 1, one hour must elapse between administration of cetuximab and bevacizumab.
Biological: Cetuximab
An initial infusion of 400 mg/m2 (over 120 minutes) on day 1 of cycle 1 with subsequent weekly infusions of 250 mg/m2 (over 60 minutes)
Biological: Bevacizumab
10 mg/kg (over 60 minutes) on day 1 and repeated every 2 weeks.
Drug: Gemcitabine
1000 mg/m2 administered intravenously at 10 mg/m2/minute over 100 minutes weekly x 3 of 4 weeks.
CB: Active Comparator
Cetuximab 400 mg/m2 weekly (over 120 minutes) on day 1 of cycle 1 with subsequent weekly infusions of 250 mg/m2 (over 60 minutes), followed by bevacizumab 10 mg/kg (over 60 minutes) on day 1 and repeated every 2 weeks. Both medications will be administered by intravenous infusion on the same day. The order of study drug administration will be cetuximab and bevacizumab. On day 1 of cycle 1, one hour must elapse between administration of cetuximab and bevacizumab.
Biological: Cetuximab
An initial infusion of 400 mg/m2 (over 120 minutes) on day 1 of cycle 1 with subsequent weekly infusions of 250 mg/m2 (over 60 minutes)
Biological: Bevacizumab
10 mg/kg (over 60 minutes) on day 1 and repeated every 2 weeks.

  Eligibility

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

Inclusion Criteria:

  • The patient has provided signed written informed consent.
  • The patient is ≥18 years of age.
  • The patient has histologically or cytologically-confirmed pancreatic adenocarcinoma not amenable to curative treatment with surgery or has documented or suspected extrapancreatic metastases.
  • The patient has either (a) measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) (see Section 11.3) or (b) non-measurable disease with an elevated baseline CA19-9 level (≥2 x the upper limit of normal [ULN]).
  • The patient's ECOG performance status is ≤2.
  • The patient has adequate hematologic function as defined by an absolute neutrophil count (ANC) ≥1500/mm3 and a platelet count ≥100,000/mm3 obtained within 2 weeks prior to the first dose of study medication.
  • The patient has adequate hepatic function as defined by a total bilirubin ≤2.0 mg/dL and transaminases ≤5.0 x ULN obtained within 2 weeks prior to the first dose of study medication.
  • The patient has adequate renal function as defined by serum creatinine ≤2.0 x ULN and urine dipstick for proteinuria ≤1+ obtained within 2 weeks prior to the first dose of study medication. If urine dipstick is ≥2+, then a 24-hour urine for protein must demonstrate < 1000 mg of protein in 24 hours to allow participation in the study. Urinalysis is also acceptable.
  • If the patient is on full-dose anticoagulation therapy (eg, warfarin or low molecular weight [LMW] heparin), the following criteria must be met:

    • The patient has an in-range INR (usually between 2 and 3) on a stable dose of oral anticoagulant or be on a stable dose of LMW heparin
    • The patient has no active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices)
  • If the patient is not on full-dose anticoagulation therapy, the following criteria must be met:

    • The patient has adequate coagulation function as defined by INR ≤1.5
    • The patient has a PTT ≤ULN obtained within 2 weeks prior to the first dose of study medication
  • If a woman, the patient agrees to use an accepted and effective method of contraception (hormonal or barrier methods, abstinence) prior to study entry and for the duration of the study. If a male and sexually active, the patient agrees to use effective contraception.
  • The patient is accessible for treatment and follow-up. Patients enrolled in this trial must be treated at the participating center.

Exclusion Criteria:

  • Endocrine tumors or lymphoma of the pancreas
  • Known brain metastases
  • Prior therapy with an EGFR inhibitor or VEGF inhibitor
  • Prior chemotherapy, hormonal therapy, or radiation therapy for advanced pancreatic cancer, patients who received chemotherapy and/or radiation therapy in the adjuvant setting will be eligible as long as the adjuvant therapy was completed >6 months prior
  • Concurrent malignancy other than non-melanomatous skin cancer or carcinoma in situ of the cervix
  • Concurrent treatment with other anti-cancer therapy, including other chemotherapy, immunotherapy, hormonal therapy, radiotherapy, chemoembolization, or targeted therapy
  • Ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations
  • History of arterial thrombotic events within 9 months
  • History of uncontrolled hypertension (>150/100 mmHg) not on a stable regimen of anti-hypertensive therapy
  • History of significant bleeding events or upper or lower gastrointestinal bleeding within 9 months
  • History of gastrointestinal perforation within 12 months
  • Serious non-healing wound ulcer, bone fracture, or major surgical procedure with 28 days
  • If a woman, is pregnant or lactating
  • An employee of the investigator or study center as well as family members of the employees
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00326911

Locations
United States, Arizona
Clopton Clinic
Jonesboro, Arizona, United States, 72401
United States, California
UCSF Comprehensive Cancer Center
San Francisco, California, United States, 94115
United States, Connecticut
Hematology Oncology, PC
Stamford, Connecticut, United States, 06902
United States, Florida
Hematology & Oncology Consultants
Orlando, Florida, United States, 32804
M. D. Anderson Cancer Center Orlando
Orlando, Florida, United States, 32806
Advanced Medical Specialties
Miami, Florida, United States, 33176
United States, Georgia
Peachtree Hematology - Oncology Consultants, PC
Atlanta, Georgia, United States, 30309
Augusta Oncology Associates, PC
Augusta, Georgia, United States, 30901
Northwest Georgia Oncology Centers, PC
Marietta, Georgia, United States, 30060
United States, Louisiana
Jayne Gurtler, MD, Laura Brinz, MD , & Angelo Russo, MD
Metairie, Louisiana, United States, 70006
United States, Montana
Hematology, Oncology Centers of the Northern Rockies, PC
Billings, Montana, United States, 59101
United States, North Carolina
NorthEast Oncology Associates
Concord, North Carolina, United States, 28025
United States, Pennsylvania
Pennsylvania Oncology Hematology Associates
Philadelphia, Pennsylvania, United States, 19106
United States, South Carolina
Charleston Cancer Center
Charleston, South Carolina, United States, 29406
United States, Texas
Arlington Cancer Center
Arlington, Texas, United States, 76012
Center for Oncology Research and Treatment, PA
Dallas, Texas, United States, 75230
Sponsors and Collaborators
ImClone LLC
Investigators
Principal Investigator: Andrew Ko, MD University of California, San Francisco
  More Information

No publications provided

Responsible Party: ImClone LLC ( Eric Rowinsky/ Chief Medical Officer )
Study ID Numbers: CP02-0555
Study First Received: May 15, 2006
Last Updated: August 6, 2009
ClinicalTrials.gov Identifier: NCT00326911     History of Changes
Health Authority: United States: Food and Drug Administration

Study placed in the following topic categories:
Antimetabolites
Anti-Infective Agents
Digestive System Neoplasms
Immunologic Factors
Pancreatic Neoplasms
Cetuximab
Endocrine System Diseases
Bevacizumab
Angiogenesis Inhibitors
Immunosuppressive Agents
Antiviral Agents
Pancrelipase
Digestive System Diseases
Radiation-Sensitizing Agents
Gastrointestinal Neoplasms
Pancreatic Diseases
Endocrinopathy
Adenocarcinoma
Gemcitabine
Endocrine Gland Neoplasms

Additional relevant MeSH terms:
Antimetabolites
Anti-Infective Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Pancreatic Neoplasms
Physiological Effects of Drugs
Bevacizumab
Neoplasms by Site
Therapeutic Uses
Growth Inhibitors
Angiogenesis Modulating Agents
Gemcitabine
Endocrine Gland Neoplasms
Digestive System Neoplasms
Growth Substances
Cetuximab
Endocrine System Diseases
Enzyme Inhibitors
Antiviral Agents
Immunosuppressive Agents
Angiogenesis Inhibitors
Pharmacologic Actions
Neoplasms
Digestive System Diseases
Radiation-Sensitizing Agents
Pancreatic Diseases

ClinicalTrials.gov processed this record on September 01, 2009