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

Sponsor:	Eastern Cooperative Oncology Group
Collaborators:	National Cancer Institute (NCI) Cancer and Leukemia Group B Southwest Oncology Group North Central Cancer Treatment Group
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00305877

Purpose

RATIONALE: Monoclonal antibodies, such as bevacizumab and cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Cetuximab may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as gemcitabine and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving bevacizumab or cetuximab together with gemcitabine, capecitabine, and radiation therapy after surgery may kill any tumor cells that remain after surgery. It is not yet known whether bevacizumab is more effective than cetuximab when given together with gemcitabine, capecitabine, and radiation therapy in treating pancreatic cancer.

PURPOSE: This randomized phase II trial is studying bevacizumab to see how well it works compared to cetuximab when given together with gemcitabine, capecitabine, and radiation therapy in treating patients with pancreatic cancer that has been completely removed by surgery.

Condition	Intervention	Phase
Pancreatic Cancer	Biological: bevacizumab Biological: cetuximab Drug: capecitabine Drug: gemcitabine hydrochloride Radiation: radiation therapy	Phase II

Study Type:	Interventional
Study Design:	Allocation: Randomized Primary Purpose: Treatment
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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Pancreatic Cancer

Drug Information available for: Gemcitabine Gemcitabine hydrochloride Capecitabine Cetuximab Bevacizumab

U.S. FDA Resources

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

Primary Outcome Measures:

Toxicity [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Overall and disease-free survival [ Designated as safety issue: No ]
Correlation between biomarkers (changes in serum alphiregulin and TGF alpha) and outcome in patients treated with cetuximab [ Designated as safety issue: No ]

Estimated Enrollment:	126
Study Start Date:	February 2006
Estimated Primary Completion Date:	August 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 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).	Biological: cetuximab Given IV Drug: capecitabine Given orally Drug: gemcitabine hydrochloride Given IV Radiation: radiation therapy Given 5 days a week for 5½ weeks
Experimental: 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.	Biological: bevacizumab Given IV Drug: capecitabine Given orally Drug: gemcitabine hydrochloride Given IV Radiation: radiation therapy Given 5 days a week for 5½ weeks

Arms

Assigned Interventions

Experimental: 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).

Biological: cetuximab

Given IV

Drug: capecitabine

Given orally

Drug: gemcitabine hydrochloride

Given IV

Radiation: radiation therapy

Given 5 days a week for 5½ weeks

Experimental: 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.

Biological: bevacizumab

Given IV

Drug: capecitabine

Given orally

Drug: gemcitabine hydrochloride

Given IV

Radiation: radiation therapy

Given 5 days a week for 5½ weeks

Detailed Description:

OBJECTIVES:

Primary

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.
Compare the safety profile of bevacizumab vs cetuximab in combination with gemcitabine hydrochloride in these regimens.
Obtain tissue specimens from these patients for correlative studies and further evaluations.

Secondary

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

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.

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

Eligibility

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

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

PATIENT CHARACTERISTICS:

ECOG performance status 0-2
WBC ≥ 3,000/mm^3
Absolute neutrophil count ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
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

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00305877

Show 360 Study Locations

Sponsors and Collaborators

Eastern Cooperative Oncology Group

National Cancer Institute (NCI)

Cancer and Leukemia Group B

Southwest Oncology Group

North Central Cancer Treatment Group

Investigators

Study Chair:	Jordan D. Berlin, MD	Vanderbilt-Ingram Cancer Center
Study Chair:	Arthur William Blackstock, MD	Comprehensive Cancer Center of Wake Forest University
Study Chair:	Andrew M. Lowy, MD	University of California, San Diego
Study Chair:	Robert McWilliams, MD	Mayo Clinic

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Featured trial article This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Robert L. Comis, ECOG Group Chair's Office
ClinicalTrials.gov Identifier:	NCT00305877 History of Changes
Other Study ID Numbers:	CDR0000462441, ECOG-E2204, CALGB-ECOG-E2204, SWOG-ECOG-E2204, NCCTG-ECOG-E2204
Study First Received:	March 21, 2006
Last Updated:	April 14, 2009
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):

stage I pancreatic cancer
stage II pancreatic cancer
duct cell adenocarcinoma of the pancreas

Additional relevant MeSH terms:

Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Gemcitabine
Capecitabine
Fluorouracil
Bevacizumab
Cetuximab
Antimetabolites, Antineoplastic
Antimetabolites

Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors

ClinicalTrials.gov processed this record on February 09, 2012