Bevacizumab or Cetuximab With Gemcitabine Hydrochloride, Capecitabine, and Radiation Therapy in Treating Patients With Pancreatic 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: September 24, 2013
Last verified: September 2013
  Purpose

This trial is designed to primarily evaluate the toxicity of two combinations of cytotoxic chemotherapy with novel non-cytotoxic therapies. Both novel agents have not been well-studied in the post-operative setting, especially with regard to pancreas cancer. Safety in that setting may not be the same as safety in other settings as these patients have several unique characteristics including slower recovery from surgery, nutritional deficiencies and significantly altered GI tract function. Both combinations have shown promise in the treatment of advanced pancreatic cancer and are in phase III trials in that setting. Both novel agents have rationale as to why they may work better (as cytostatic agents) in a minimal residual disease setting than in a metastatic setting and therefore may have benefits in an adjuvant setting without significant benefit in the metastatic setting. Therefore, a smaller phase II trial of both agents in the adjuvant setting is realistic for determining the toxicity profile in this unique adjuvant setting. Additionally, as the results of three large cooperative group studies become available with potentially better outcomes with bevacizumab, cetuximab or oxaliplatin in combination with gemcitabine, the data on efficacy from this trial may help to elucidate the best option for study in future phase III adjuvant trials.


Condition Intervention Phase
Pancreatic Cancer
Biological: cetuximab
Drug: gemcitabine hydrochloride
Drug: capecitabine
Radiation: radiotherapy
Biological: bevacizumab
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: January 2013
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A (cetuximab, gemcitabine, capecitabine, radiation)
Patients receive cetuximab intravenously (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
  • NSC 714692
  • Erbitux
Drug: gemcitabine hydrochloride
Given IV
Other Names:
  • 2'-Deoxy-2'
  • 2'-difluorocytidine monohydrochloride
  • Gemzar
  • gemcitabine
Drug: capecitabine
Given orally
Other Name: Xeloda
Radiation: radiotherapy
Undergo radiation therapy
Other Names:
  • irradiation
  • radiation therapy
Experimental: Arm B (bevacizumab, gemcitabine, capecitabine, radiation)
Patients receive bevacizumab IV over 60-90 minutes on day 1 every other week for 24 weeks. Patients also receive gemcitabine hydrochloride and capecitabine and undergo radiotherapy as in Arm A.
Drug: gemcitabine hydrochloride
Given IV
Other Names:
  • 2'-Deoxy-2'
  • 2'-difluorocytidine monohydrochloride
  • Gemzar
  • gemcitabine
Drug: capecitabine
Given orally
Other Name: Xeloda
Radiation: radiotherapy
Undergo radiation therapy
Other Names:
  • irradiation
  • radiation therapy
Biological: bevacizumab
Given IV
Other Names:
  • NSC 704865
  • RhuMAb VEGF
  • Recombinant Humanized Monoclonal Anti-VEGF Antibody

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 transforming growth factor (TGF) alpha to survival, disease-free survival 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 A: 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 B: 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 5 years.

  Eligibility

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

Inclusion Criteria:

  • Histologically or cytologically confirmed evidence of pancreatic carcinoma
  • All gross disease resected (R0 or R1 resection)
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
  • Normal organ and marrow function measured within 4 weeks prior to randomization
  • 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

Exclusion Criteria:

  • R2 resection
  • Prior chemotherapy or radiation therapy for pancreatic cancer
  • Prior epidermal growth factor receptor (EGFR)/vascular endothelial growth factor (VEGF) inhibition
  • Pregnant or breast-feeding
  • Receiving other investigational agents
  • Known metastases
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to cetuximab, bevacizumab or other agents used in the study
  • Patients with wounds that have not fully healed
  • Cardiac arrhythmia
  • Known HIV infection
  • Acinar cell carcinoma, neuroendocrine carcinoma, cystadenocarcinoma, carcinosarcoma
  • Psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude them from meeting the study requirements
  • Requiring full dose anticoagulation
  • History of transient ischemic attack (TIA) or cerebrovascular accident (CVA)
  • History of the following within twelve months of study entry:

    • Arterial thromboembolic events
    • Unstable angina
    • Myocardial infarction
  Contacts and Locations
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, E2204, U10CA021115
Study First Received: March 21, 2006
Results First Received: September 24, 2013
Last Updated: September 24, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
Bevacizumab
Cetuximab
Chemoradiation
Pancreatic carcinoma

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 April 17, 2014