Phase 2
N=64
FOLFOX +/- Ziv-Aflibercept for Esophageal and Gastric Cancer
Esophageal Cancer · Gastric Cancer
Bottom Line
View on ClinicalTrials.gov: NCT01747551 ↗Enrolled (actual)
64
Serious AEs
67.2%
Results posted
May 2018
Primary outcome: Primary: 6-month Progression-free Survival (PFS) — 60.5; 57.1 percent probability — p=0.72
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Oxaliplatin (Drug); Leucovorin (Drug); Fluorouracil (Drug); Ziv-aflibercept (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Dana-Farber Cancer Institute
- Primary completion
- Nov 2016
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY 6-month Progression-free Survival (PFS) |
60.5; 57.1 | 0.72 |
| SECONDARY Grade 4 Treatment-Related Toxicity Rate |
11.6; 9.5 | — |
| SECONDARY Objective Response Rate (ORR) |
61.1; 75.0 | — |
| SECONDARY Duration of Objective Response |
9.0; 8.0 | — |
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).
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% 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
Data sourced from ClinicalTrials.gov (NCT01747551). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.