Cetuximab and Bevacizumab With or Without Gemcitabine to Treat Metastatic Pancreatic Cancer

NCT00326911 | Terminated Phase 2 Results DMC

• 1 other identifier: CP02-0555
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 16

Brief Summary

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

Conditions

Metastatic Pancreatic Cancer

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS)

  Progression-free survival is the time from randomization until the date of progressive disease (PD) or death from any cause whichever is first reported. Patients who die without a reported prior progression were considered to have progresssed on the day of their death. Patients who did not progress were censored at the day of their last tumor assessment.

  Time from randomization to disease progression or death from any cause (Range: 0 -10 months)

Secondary Outcomes (22)

• Overall Survival (OS)

  Survival information was collected continuously every 3 months after completion of therapy and/or follow-up (range: 1-19 months).

• The Number of Patients With a Best Overall Response of Either a Complete Response (CR) or Partial Response (PR)

  Tumor evaluations were performed every 8 weeks while on cetuximab therapy until PD or recurrence. Patients with a PR or CR had a confirmatory tumor assessment no less than 4 weeks after the initial evaluation.

• Percentage of Patients With Carbohydrate Antigen 19-9 (CA19-9) Response at End of Cycle 2 in Patients With Elevated Baseline Values (Equal or Greater Than 2 x Upper Limit of Normal).

  First day of treatment to the end of Cycle 2, Week 1

• Time to Progression (TTP)

  Time from randomization until the date of objective tumor progression was first reported (range: 11 -38 months)

• Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

  An AE was included in the safety analysis if its onset date occurred anytime during cetuximab treatment or up to 30 days after the last dose of cetuximab.

Study Arms (2)

cetuximab + bevacizumab + gemcitabine

EXPERIMENTAL

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. All 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; Biological: bevacizumab; Drug: gemcitabine

cetuximab + bevacizumab

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; Biological: bevacizumab

Interventions

cetuximab BIOLOGICAL

I.V. infusion of 400 mg/m2 (over 120 minutes) on day 1 of cycle 1

Also known as: Erbitux®

cetuximab + bevacizumab; cetuximab + bevacizumab + gemcitabine

bevacizumab BIOLOGICAL

10 mg/kg (over 60 minutes) on day 1 and repeated every 2 weeks.

Also known as: Avastin®

cetuximab + bevacizumab; cetuximab + bevacizumab + gemcitabine

gemcitabine DRUG

1000 mg/m2 administered intravenously at 10 mg/m2/minute over 100 minutes weekly x 3 of 4 weeks.

Also known as: Gemzar®

cetuximab + bevacizumab + gemcitabine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 Version 1.0 (RECIST) or (b) non-measurable disease with an elevated baseline CA19-9 level (≥2 x the upper limit of normal \[ULN\]).
• The patient's Eastern Cooperative Oncology Group (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 International Normalized Ratio (\[INR\]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 partial thromboplastin (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.

You may not qualify if:

• Endocrine tumors or lymphoma of the pancreas
• Known brain metastases
• Prior therapy with an epidermal growth factor receptor (EGFR) inhibitor or vascular endothelial growth factor (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

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (16)

ImClone Investigational Site

Jonesboro, Arkansas, 72401, United States

Location

ImClone Investigational Site

San Francisco, California, 94115, United States

Location

ImClone Investigational Site

Stamford, Connecticut, 06902, United States

Location

ImClone Investigational Site

Miami, Florida, 33176, United States

Location

ImClone Investigational Site

Orlando, Florida, 32804, United States

Location

ImClone Investigational Site

Orlando, Florida, 32806, United States

Location

ImClone Investigational Site

Atlanta, Georgia, 30309, United States

Location

ImClone Investigational Site

Augusta, Georgia, 30901, United States

Location

ImClone Investigational Site

Marietta, Georgia, 30060, United States

Location

ImClone Investigational Site

Metairie, Louisiana, 70006, United States

Location

ImClone Investigational Site

Billings, Montana, 59101, United States

Location

ImClone Investigational Site

Concord, North Carolina, 28025, United States

Location

ImClone Investigational Site

Philadelphia, Pennsylvania, 19106, United States

Location

ImClone Investigational Site

Charleston, South Carolina, 29406, United States

Location

ImClone Investigational Site

Arlington, Texas, 76012, United States

Location

ImClone Investigational Site

Dallas, Texas, 75230, United States

Location

Related Publications (1)

• Ko AH, Youssoufian H, Gurtler J, Dicke K, Kayaleh O, Lenz HJ, Keaton M, Katz T, Ballal S, Rowinsky EK. A phase II randomized study of cetuximab and bevacizumab alone or in combination with gemcitabine as first-line therapy for metastatic pancreatic adenocarcinoma. Invest New Drugs. 2012 Aug;30(4):1597-606. doi: 10.1007/s10637-011-9691-8. Epub 2011 Jun 1.

  PMID: 21629990 DERIVED

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Cetuximab; Bevacizumab; Gemcitabine

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Limitations and Caveats

Accrual on the trial was stopped earlier than planned due to insufficient efficacy in both arms.

Results Point of Contact

• Title: Chief Medical Officer
• Organization: ImClone LLC

ClinicalTrials@ImClone.com

Study Officials

• E-mail: ClinicalTrials@ ImClone.com

  Eli Lilly and Company

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: May 15, 2006
• First Posted: May 17, 2006
• Study Start: May 1, 2006
• Primary Completion: October 1, 2008
• Study Completion: December 1, 2008
• Last Updated: May 25, 2011
• Results First Posted: December 4, 2009

Record last verified: 2011-05

Locations

US (16)