FOLFOX +/- Ziv-Aflibercept for Esophageal and Gastric Cancer
Esophageal Cancer, Gastric Cancer
About this trial
This is an interventional treatment trial for Esophageal Cancer focused on measuring Advanced
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
Sites / Locations
- Massachusetts General Hospital
- Dana-Farber Cancer Institute
Arms of the Study
Arm 1
Arm 2
Active Comparator
Active Comparator
mFOLFOX6 + Ziv-aflibercept
mFOLFOX6 + Placebo
Patients received mFOLFOX6 and ziv-aflibercept every 2 weeks. Ziv-aflibercept 4mg/kg was given via intravenous (IV) infusion over 1 hour. Immediately following this was administration of mFOLFOX6: oxaliplatin 85 mg/m2 IV and leucovorin 400 mg/m2 IV were given concurrently over 120 minutes, followed by fluorouracil 400 mg/m2 IV bolus injection and then fluorouracil 2,400 mg/m2 IV infusion over 46 hours. Patients continued on treatment until radiological or clinical progression, unacceptable toxicity, or death.
Patients received mFOLFOX6 and placebo every 2 weeks. Placebo was given via intravenous (IV) infusion over 1 hour. Immediately following this was administration of mFOLFOX6: oxaliplatin 85 mg/m2 IV and leucovorin 400 mg/m2 IV were given concurrently over 120 minutes, followed by fluorouracil 400 mg/m2 IV bolus injection and then fluorouracil 2,400 mg/m2 IV infusion over 46 hours. Patients continued on treatment until radiological or clinical progression, unacceptable toxicity, or death.