FOLFOX +/- Ziv-Aflibercept for Esophageal and Gastric Cancer
Condition: Esophageal Cancer; Gastric Cancer
MeSH terms: Stomach Neoplasms
Intervention: Oxaliplatin; Leucovorin; Fluorouracil; Ziv-aflibercept
Intervention MeSH terms: Leucovorin; Fluorouracil; Oxaliplatin; Aflibercept
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Enrollment: 64.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Advanced

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% 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