Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Related Information
Registry Information

Alternate Title

Bevacizumab or Cetuximab Combined With Gemcitabine, Capecitabine, and Radiation Therapy in Treating Patients With Pancreatic Cancer That Has Been Completely Removed By Surgery

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Biomarker/Laboratory analysis, Treatment Closed 18 and over NCI ECOG-E2204 CALGB-ECOG-E2204, SWOG-ECOG-E2204, NCCTG-ECOG-E2204, E2204, NCT00305877

Special Category: NCI Web site featured trial, NCI - CMS pilot project trial

Objectives

Primary

1. Compare the toxicity profile of adjuvant therapy comprising bevacizumab vs cetuximab in combination with gemcitabine hydrochloride, capecitabine, and radiotherapy in patients with completely resected carcinoma of the pancreas.
2. Compare the safety profile of bevacizumab vs cetuximab in combination with gemcitabine hydrochloride in these regimens.
3. Obtain tissue specimens from these patients for correlative studies and further evaluations.

Secondary

1. Compare disease-free and overall survival of patients treated with these regimens.
2. Compare the safety profile of these regimens in these patients.
3. Compare the 2-year survival rate in patients treated with these regimens.

Entry Criteria

Disease Characteristics:

• Histologically or cytologically confirmed carcinoma of the pancreas



• Underwent prior surgical resection of all gross disease more than 4 but no more than 8 weeks ago
  • R0 (surgical margins clear) or R1 (microscopic involvement of margins) resection
  • No R2 resection



• No acinar cell carcinoma, neuroendocrine carcinoma, cystadenocarcinoma, or carcinosarcoma



• No known metastases

Prior/Concurrent Therapy:

• See Disease Characteristics
• Recovered from prior surgery
• No prior chemotherapy or radiotherapy for pancreatic cancer
• No prior epidermal growth factor receptor or vascular epithelial growth factor inhibitors
• No other concurrent investigational agents
• No concurrent full-dose anticoagulation
• No concurrent intensity-modulated radiotherapy

Patient Characteristics:

• ECOG performance status 0-2
• WBC ≥ 3,000/mm³
• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Bilirubin normal
• AST/ALT ≤ 2.5 times upper limit of normal (ULN)
• Creatinine normal

  OR

• Creatinine clearance ≥ 60 mL/min
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for ≥ 6 months after completion of study treatment
• No history of allergic reactions attributed to compounds of similar chemical or biologic composition to cetuximab, bevacizumab, or other agents used in study
• No cardiac arrhythmia
• No known HIV infection
• No unhealed wound
• No psychiatric or addictive disorders or other condition that would preclude study participation
• No history of transient ischemic attack or cerebrovascular accident
• No arterial thromboembolic event within the past year
• No unstable angina within the past year
• No myocardial infarction within the past year

Expected Enrollment

A total of 126 patients will be accrued for this study.

Outcomes

Toxicity

Overall and disease-free survival
Correlation between biomarkers (changes in serum alphiregulin and TGF alpha) and outcome in patients treated with cetuximab

Outline

This is a randomized, multicenter study. Patients are stratified according to degree of prior resection of the pancreatic tumor (R0 vs R1). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive cetuximab IV over 60-120 minutes on day 1, once weekly, in weeks 1-24; gemcitabine hydrochloride IV over 30 minutes on day 1, once weekly, in weeks 1-3, 13-15, 17-19, and 21-23; oral capecitabine twice daily on days 1-5, 5 days a week, in weeks 5-10. Patients also undergo radiotherapy once daily, 5 days a week, beginning in week 5 and continuing for approximately 5½ weeks (25 fractions).



• Arm II: Patients receive bevacizumab IV over 60-90 minutes on day 1 in weeks 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, and 23. Patients also receive gemcitabine hydrochloride and capecitabine and undergo radiotherapy as in arm I.

In both arms, treatment continues in the absence of disease progression or unacceptable toxicity.

Tumor samples are analyzed for epidermal growth factor receptor (EGFR) status and microvessel density.

After completion of study treatment, patients are followed periodically for up to 3 years.

Trial Contact Information

Trial Lead Organizations

Eastern Cooperative Oncology Group

Jordan Berlin, MD, Protocol chair		Ph: 615-322-4967; 800-811-8480 Email: jordan.berlin@vanderbilt.edu

Cancer and Leukemia Group B

Arthur William Blackstock, MD, Protocol chair		Ph: 336-713-6501; 800-446-2255

Southwest Oncology Group

Andrew Lowy, MD, Protocol chair		Ph: 858-822-5354

North Central Cancer Treatment Group

Robert McWilliams, MD, Protocol chair		Ph: 507-284-2511

Related Information

Featured trial article

Registry Information
Official Title		An Intergroup Randomized Phase II Study of Bevacizumab (NSC 704865) or Cetuximab (NSC 714692) in Combination with Gemcitabine and in Combination with Chemoradiation (Capecitabine and Radiation) in Patients with Completely-Resected Pancreatic Carcinoma
Trial Start Date		2006-02-17
Trial Completion Date		2008-08-31 (estimated)
Registered in ClinicalTrials.gov		NCT00305877
Date Submitted to PDQ		2005-11-28
Information Last Verified		2008-10-22
NCI Grant/Contract Number		CA21115