A Phase II Study of Pre-operative Chemotherapy Plus Bevacizumab With Early Salvage Therapy Based on PET Assessment of Response in Patients With Locally Advanced But Resectable Gastric and GEJ Adenocarcinoma
Overview
- Phase
- Phase 2
- Intervention
- epirubicin, cisplatin, capecitabine, bevacizumab, docetaxel and irinotecan
- Conditions
- Esophageal Cancer
- Sponsor
- Memorial Sloan Kettering Cancer Center
- Enrollment
- 22
- Locations
- 2
- Primary Endpoint
- Overall Response Will be Characterized by the Patient's FDG-PET Scan
- Status
- Completed
- Last Updated
- 10 years ago
Overview
Brief Summary
This study is being done to find out how effective a new treatment strategy is on your cancer. In this strategy, the response your tumor has to the first cycle of therapy will help select the next treatments. We also will find out the effects, both good and/or bad, a drug called bevacizumab has on you and your tumor when given with chemotherapy.
Investigators
Eligibility Criteria
Inclusion Criteria
- •All patients must have microscopically confirmed adenocarcinoma of the stomach or GE junction. Tumors involving the GE junction must have the bulk of their disease in the stomach; tumors of the distal esophagus that extend less than 2cm into the stomach are ineligible for this study.
- •All patients must be considered candidates for surgical resection.
- •Patients must have FDG-avid malignancies.
- •FDG avid tumors are defined as primary tumors with an increased tracer uptake in the region of the tumor that has an SUV \> or = to 3.5 or a tumor:liver ratio \> or = to 1.5, and felt to be "probably" or "definitely malignant" (i.e. likelihood score of 3 or 4) by the reference nuclear medicine physician.
- •All patients must have localized cancer potentially curable by surgery. The tumor stage should be T any N+ M0 or T3-T4a N any M0(AJCC 7th Edition), by staging that includes a CT scan and either laparoscopy or endoscopic ultrasound. Patients with T1-2 N0M0 or patients with distant metastatic disease (i.e. M1) are ineligible. Any sites of suspected M1 disease by these criteria must be proven to be M0 prior to entrance into the neoadjuvant study.
- •Patients may not have received prior chemotherapy or radiation for this disease.
- •The patient is at least 18 years of age.
- •If female and of child bearing potential, the patient has a negative serum pregnancy test within 14 days of starting therapy, and, if male or female and of child bearing potential, currently uses (and agree to continue to use throughout the study) an acceptable method of birth control (IUD, oral contraceptive, or barrier device). They should agree to continue to use these for three months after the study is completed. The patient also agrees to refrain from nursing during the duration of the study and for at least two months after the study is completed. Pregnant or lactating females are not included because the anti-proliferative effects of bevacizumab may be harmful to the fetus or developing infant.
- •Karnofsky performance status \> or = to 70%.
- •The patient has adequate hematopoietic function, defined as having a total neutrophil count (ANC) ≥ or = to 1500/mm3, a platelet count ≥ or = 100,000/mm
Exclusion Criteria
- •Any metastatic disease.
- •Significant cardiac disease as defined as:
- •New York Heart Association (NYHA) grade II or greater (see Appendix B for NYHA Class),
- •congestive heart failure, or history of myocardial infarction or unstable angina within 12 months of study enrollment
- •Any history of stroke or transient ischemic attack at any time.
- •Pregnant (positive pregnancy test) or lactating women. A pregnancy test will be performed on sexually active women of childbearing potential prior to entry into the study. Treatment may not begin until the results of the pregnancy test are ascertained.
- •Inadequately controlled hypertension (defined as systolic blood pressure \> 150 mmHg and/or diastolic blood pressure \> 100 mmHg) on antihypertensive therapy.
- •Any prior history of hypertensive crisis or hypertensive encephalopathy.
- •Significant vascular disease (e.g. aortic aneurysm, aortic dissection)
- •Symptomatic peripheral vascular disease (ie. grade 2 or higher).
Arms & Interventions
1
Initial chemo for ALL pts (ECX + BEV): Epirubicin 50 mg/m2 d1 every 21 days Cisplatin 60 mg/m2 d1 every 21 days, Capecitabine 625 mg/m2 po bid days 2-21 (held for 48 hours prior to FDG-PET/CT in week 3) Bev 15 mg/kg d1 every 21 days (cycle 1 \& cycle 2 only) Salvage chemotherapy for metabolic non-responders (DI + BEV): Docetaxel 30 mg/m2 d1, d8 every 21 days, CPT-11 50 mg/m2 d1, d8 every 21 days, Bev 15 mg/kg d1, cycle 2 only 2 cycles are planned prior to resection. Pts who aren't Cisplatin candidates (i.e. Creatinine clearance 40-60/cc, older age, marginal PS,etc.) may get oxaliplatin instead of cisplatin after discus with the PI. Oxaliplatin will be admin at 130 mg/m2 on day 1 every 21 days. Pts who aren't able to get Capecitabine (i.e. insurance restriction, unable to swallow, etc.) may get infusional fluorouracil instead of capecitabine after discus with the PI. Fluorouracil will be admin at 200 mg/m2/d x 21 days (held for 48 hours prior to FDGPET/ CT scan in week 3 of cycle 1).
Intervention: epirubicin, cisplatin, capecitabine, bevacizumab, docetaxel and irinotecan
Outcomes
Primary Outcomes
Overall Response Will be Characterized by the Patient's FDG-PET Scan
Time Frame: 2 years
A good early FDG Response is a reduction in FDG uptake on the week 3 PET scan of \> or = to 35% from baseline. An FDG PET non-responder will be defined as having a decrease of \< 35% on the week 3 PET scan compared with baseline.