FOLFOX +/- Ziv-Aflibercept for Esophageal and Gastric Cancer

Status: Recruiting
Phase: Phase 2
Diagnosis: Gastrointestinal Malignancies, Esophageal Cancer, Stomach Cancer
NCT ID: NCT01747551 (View complete trial on ClinicalTrials.gov)
DFCI Protocol ID: 12-401

 

This research study is a Phase II clinical trial to test the safety and effectiveness of the investigational drug Ziv-aflibercept in combination with mFOLFOX6 compared to mFOLFOX6 alone. The drugs used in mFOLFOX6 include Fluorouracil (5-FU), Leucovorin and Oxaliplatin. In patients with esophagogastric cancer, mFOLFOX6 has been used in both clinical trials and standard of care. "Investigational" means that the FDA has not yet approved this combination for the treatment of esophagogastric cancer. Every person has molecules in their bloodstream called vascular endothelial growth factors (VEGFs). These molecules help grow and sustain new blood vessels needed by the human body. Cancer tumors hijack this mechanism because they need new blood vessels and oxygen to grow. Ziv-aflibercept is an antibody, a "targeted therapy" called a "VEGF Trap", that "traps" (binds) these VEGFs and prevents the cancer from using them to grow. Ziv-aflibercept has recently been approved by the FDA for patients with treatment-resistant colorectal cancer. Patients who received standard 5-fluoruracil based chemotherapy pus ziv-aflibercept lived significantly longer than those patients who received standard 5-fluoruracil alone. In this research study, investigators will see if adding ziv-aflibercept to standard chemotherapy (mFOLFOX6) works better than mFOLFOX6 chemotherapy alone in patients with metastatic or unresectable esophagogastric cancer.

 

Conducting Institutions:
Dana-Farber Cancer Institute, Brigham and Women's Hospital, Massachusetts General Hospital

Overall PI:
Peter Enzinger, MD, Dana-Farber Cancer Institute

Site-responsible Investigators:
Eunice Kwak, MD, Massachusetts General Hospital

Contacts:
Dana-Farber Cancer Institute: Gastrointestinal Research Line, 617-632-5960
Massachusetts General Hospital: Cancer Trials Call Center, 877-789-6100

Eligibility Criteria

Inclusion Criteria: - Confirmed adenocarcinoma of esophagus, GE junction or gastric origin - Disease is not amenable to curative resection and is unresectable, locally advanced or metastatic - Have not received any prior chemotherapy, investigative or biologic agents for esophagogastric cancer except in the neoadjuvant or adjuvant setting - Any major surgery must be completed at least 4 weeks prior to study entry, minor procedures must be completed at least 2 weeks prior to study entry - Vascular access device insertion should be performed at least 1 week prior to study entry. A central line is recommended for all participants - Willing to use adequate contraception prior to study entry, for the duration of study participation and for 3 months after the last dose of Ziv-aflibercept/placebo Exclusion Criteria: - History of hypertension unless adequately controlled - Evidence of active bleeding from primary tumor at time of study entry - Pregnant or breastfeeding - Squamous cell carcinoma histology - Prior treatment for advanced or metastatic disease - Palliative radiation to < 25% of bone marrow must have been completed 2 weeks prior to study entry, palliative RT to > 25% must have been completed 4 weeks prior to study entry - Known allergy to study agents - Known dihydropyrimidine dehydrogenase deficiency or thymidylate kinase gene polymorphism predisposing participant to 5-FU toxicity - History of symptomatic congestive heart failure - Clinically significant peripheral arterial disease - Grade 2 or higher sensory or motor neuropathy - Serious unhealed wound, ulcers or bone fractures - History of HIV positivity or hepatitis B or C - History of abdominal fistula, wound dehiscence, GI perforation, intra abdominal abscess, uncontrolled GI bleeding or diverticulitis that required hospitalization within 6 months of study entry - History of arterial thrombotic events - History of CNS hemorrhage in past 6 months - Use of warfarin - History of prior or synchronous malignancy except if treated with curative intent more than 3 years prior to enrollment, or adequately treated non-melanoma skin cancers, cervical carcinoma in situ or prostatic intraepithelial neoplasia without evidence of prostate cancer - Uncontrolled non-malignant illness - Uncontrolled psychiatric illness
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