Clinical trial · Interventional
FOLFOX +/- Ziv-Aflibercept for Esophageal and Gastric Cancer
Randomized, Double-Blind, Placebo Controlled Phase II Study of FOLFOX +/- Ziv-Aflibercept in Patients With Advanced Esophageal and Gastric Cancer
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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).
Conditions
Conditions (2)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Esophageal Cancer | Malignant Esophageal Neoplasm | CURATED_EXACT | 0.92 |
| Gastric Cancer | Malignant Gastric Neoplasm | CURATED_BROADER | 0.80 |
Interventions
Interventions (4)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Fluorouracil | Drug | Fluorouracil | ALIAS |
| Leucovorin | Drug | Leucovorin | ALIAS |
| Oxaliplatin | Drug | Oxaliplatin | ALIAS |
| Ziv-aflibercept | Drug | Aflibercept | ALIAS |
Design
Arms and outcomes
Arms (2)
- type
- ACTIVE_COMPARATOR
- label
- mFOLFOX6 + Ziv-aflibercept
- description
- 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.
- interventionNames
- Drug: Oxaliplatin
- Drug: Leucovorin
- Drug: Fluorouracil
- Drug: Ziv-aflibercept
- type
- ACTIVE_COMPARATOR
- label
- mFOLFOX6 + Placebo
- description
- 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.
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
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
References
Publications (0)
Data not yet available