|Phase II||Biomarker/Laboratory analysis, Treatment||Completed||18 and over||NCI||NCI-2012-02969|
E2204, U10CA021115, ECOG-E2204, CALGB-ECOG-E2204, SWOG-ECOG-E2204, NCCTG-ECOG-E2204, NCT00305877
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.
Further Study Information
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.
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.
- 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
- 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
Trial Lead Organizations/Sponsors
National Cancer Institute
|Jordan Berlin||Principal Investigator|
Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00305877
ClinicalTrials.gov processed this data on November 26, 2013
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