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

• Status: Completed
• Trial end date: 2017-07-26
• Target enrollment: 0
• Participant gender: All

Summary

Anti-angiogenic therapy is a proven therapeutic target in refractory gastric and gastroesophageal junction adenocarcinoma. This trial assessed whether the addition of a high affinity angiogenesis inhibitor, ziv-aflibercept, could improve the efficacy of first-line mFOLFOX6 (oxaliplatin, leucovorin, and bolus plus infusional 5- fluorouracil) chemotherapy in metastatic esophagogastric adenocarcinoma.

In this study (ZAMEGA), patients with treatment-naïve esophagogastric adenocarcinoma were randomly assigned 2:1 in a multicenter, placebo-controlled double-blind trial to receive first-line mFOLFOX6 with or without ziv-aflibercept 4mg/kg every 2 weeks. Randomization was stratified by ECOG performance status (0-1 vs. 2) and primary site of disease (esophagus or GE junction vs stomach).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Dana-Farber Cancer Institute
• Treatments: Aflibercept; Fluorouracil; Folic Acid; Leucovorin; Levoleucovorin; Oxaliplatin

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