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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00305877
First received: March 21, 2006
Last updated: May 6, 2014
Last verified: December 2012
  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. 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.


Condition Intervention Phase
Stage IA Pancreatic Cancer
Stage IB Pancreatic Cancer
Stage IIA Pancreatic Cancer
Stage IIB Pancreatic Cancer
Biological: cetuximab
Drug: gemcitabine hydrochloride
Drug: capecitabine
Radiation: radiation therapy
Biological: bevacizumab
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
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:


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

Primary Outcome Measures:
  • Proportion of Patients With Specific Protocol Defined Adverse Event at Conclusion of All Therapy [ Time Frame: Every 2 weeks while on treatment and for 30 days after the end of treatment ] [ Designated as safety issue: Yes ]

    Specific toxicities to be monitored pursuant to the primary endpoint include:

    1. Any grade 5 toxicities
    2. Grade 4 dyspnea, neutropenic fever, allergic reaction, rash, wound dehiscence, wound infection, hypertension
    3. Grade 3 or higher arterial thromboembolic phenomena, bleeding, phlebitis/deep vein thrombosis (DVT)/pulmonary embolism (PE), hemorrhage, ileus, bowel perforation, diarrhea, and mucositis
    4. ECOG performance status decline by 2 or greater for >24 hours
    5. Weight loss >10%


Secondary Outcome Measures:
  • Two-year Overall Survival Rate [ Time Frame: Assessed every 3 months for 2 years ] [ Designated as safety issue: No ]
    Overall survival (OS) is defined as the time from randomization to death from any cause, or censored at last known date of survival.

  • Two-year Disease-free Survival (DFS) [ Time Frame: Assessed every 3 months for 2 years, and every 6 months after completion of treatment for 2 years, then annually for 3 years ] [ Designated as safety issue: No ]
    Disease-free survival (DFS) is defined as the time from randomization to the first treatment failure (recurrence or death before recurrence).


Enrollment: 137
Study Start Date: February 2006
Study Completion Date: February 2012
Primary Completion Date: July 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (cetuximab, gemcitabine, capecitabine, radiation)
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
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
Drug: capecitabine
Given orally
Other Names:
  • CAPE
  • Ro 09-1978/000
  • Xeloda
Radiation: radiation therapy
Undergo radiation therapy
Other Names:
  • irradiation
  • radiotherapy
  • therapy, radiation
Other: laboratory biomarker analysis
Correlative studies
Experimental: Arm II (bevacizumab, gemcitabine, capecitabine, radiation)
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.
Drug: gemcitabine hydrochloride
Given IV
Other Names:
  • dFdC
  • difluorodeoxycytidine hydrochloride
  • gemcitabine
  • Gemzar
Drug: capecitabine
Given orally
Other Names:
  • CAPE
  • Ro 09-1978/000
  • Xeloda
Radiation: radiation therapy
Undergo radiation therapy
Other Names:
  • irradiation
  • radiotherapy
  • therapy, radiation
Biological: bevacizumab
Given IV
Other Names:
  • anti-VEGF humanized monoclonal antibody
  • anti-VEGF monoclonal antibody
  • Avastin
  • rhuMAb VEGF
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To describe the toxicity profile of cetuximab and bevacizumab when combined with gemcitabine, before and after capecitabine plus radiation and during capecitabine plus radiation in patients with completely-resected pancreatic carcinoma in the adjuvant setting.

II. To assess the safety profile of either cetuximab or bevacizumab plus gemcitabine in patients with resected pancreatic cancer.

III. To obtain tissue specimens from resections of patients enrolled on study for correlative studies and further evaluations.

SECONDARY OBJECTIVES:

I. To evaluate disease-free and overall survival for patients receiving either cetuximab or bevacizumab in combination with gemcitabine before and after capecitabine plus radiation.

II. To assess the safety profile for patients receiving either capecitabine plus cetuximab plus radiation, or capecitabine plus bevacizumab plus radiation.

III. To correlate changes in serum amphiregulin and TGF alpha to survival, DFS and rash for patients receiving cetuximab.

IV. To determine the 2-year survival rate for patients receiving either cetuximab plus gemcitabine before and after capecitabine plus cetuximab plus radiation, or bevacizumab plus gemcitabine before and after capecitabine plus bevacizumab plus radiation.

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.

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

  Eligibility

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

Inclusion Criteria:

  • Patients must have histologically or cytologically confirmed evidence of pancreatic carcinoma
  • Patients must have had all gross disease resected (R0 or R1 resection)
  • Patients undergoing an R2 resection are not eligible
  • Patients must have had no prior chemotherapy or radiation therapy for pancreatic cancer and must have had no prior EGFR/VEGF inhibition
  • Patient must have ECOG performance status of 0-2
  • Leukocytes >= 3,000/μL
  • ANC >= 1,500/μL
  • Platelets >= 100,000/μL
  • Total bilirubin Within normal institutional limits
  • AST (SGOT)/ALT(SGPT) =< 2.5 X institutional upper limit of normal
  • Creatinine clearance >= 60 mL/min for patients with creatinine levels above institutional normal
  • Patients must be > 4 weeks and =< 8 weeks post-surgery at time of study registration (may be up to 10 weeks post-surgery prior to start of study therapy)
  • Women of childbearing potential and sexually active males are strongly advised to use an accepted and effective method of contraception prior to study entry
  • Women must not be pregnant or breast-feeding; all agents used in this study as well as radiation therapy to the abdomen have the potential for teratogenic or abortifacient effects; all females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy
  • Patients must not be receiving any other investigational agents
  • Patients with known metastases are not eligible
  • Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to cetuximab, bevacizumab or other agents used in the study are not eligible
  • Patients with wounds that have not fully healed are not eligible
  • Patients must not have cardiac arrhythmia
  • Patients must have no known HIV infection
  • Patients must not have any of the following: acinar cell carcinoma, neuroendocrine carcinoma, cystadenocarcinoma, carcinosarcoma
  • Patients with psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude them from meeting the study requirements are not eligible
  • Patients requiring full dose anticoagulation are not eligible
  • Patients with a history of transient ischemic attack (TIA) or cerebrovascular accident (CVA) are not eligible
  • Patients with a history of the following within twelve months of study entry are not eligible:

    • Arterial thrombembolic events
    • Unstable angina
    • Myocardial infarction
  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: NCT00305877

Locations
United States, Massachusetts
Eastern Cooperative Oncology Group
Boston, Massachusetts, United States, 02215
Sponsors and Collaborators
Investigators
Principal Investigator: Jordan Berlin Eastern Cooperative Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00305877     History of Changes
Other Study ID Numbers: NCI-2012-02969, NCI-2012-02969, CALGB-ECOG-E2204, SWOG-ECOG-E2204, ECOG-E2204, NCCTG-ECOG-E2204, E2204, E2204, U10CA021115
Study First Received: March 21, 2006
Results First Received: September 24, 2013
Last Updated: May 6, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Antibodies
Antibodies, Monoclonal
Gemcitabine
Fluorouracil
Capecitabine
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
Radiation-Sensitizing Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents

ClinicalTrials.gov processed this record on August 27, 2014