Nintedanib Plus mFOLFOX6 for Previously Untreated Metastatic Esophagogastric Adenocarcinoma (MEGAN)

NCT02856867 | Withdrawn Phase 2

• 2 other identifiers: EORTC-1418-GITCG2016-002361-58
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a prospective, multicenter, randomized, placebo-controlled, triple-blind phase II trial. The randomization will be a 1:1 randomization (experimental arm:control arm). This study will enroll patients with histologically confirmed esophagogastric adenocarcinoma with metastatic disease. Patients will have had no previous chemotherapy for metastatic esophagogastric cancer. Patients will receive nintedanib or placebo in combination with mFOLFOX6 (5-Fluorouracil 400 mg/m2 bolus on day 1, 5-Fluorouracil 2400 mg/m2 continuous infusion over 46 hours starting on day 1, Leucovorin 400 mg/m2 on day 1, Oxaliplatin 85 mg/m2 on day 1) via IV infusions every 2 weeks (14 days). Dose modification of nintedanib or placebo and mFOLFOX6 is allowed. Patients may continue to receive protocol therapy as long as they have not experienced any adverse events requiring permanent discontinuation of study medication and have not demonstrated disease progression. The primary objective is to test the hypothesis that progression free survival (PFS) is prolonged in HER2-negative patients with untreated metastatic esophagogastric adenocarcinoma when treated with nintedanib plus modified FOLFOX6 (mFOLFOX6) as compared to placebo plus mFOLFOX6. The analyses will be performed when 124 events for PFS will have been observed in the pooled arms.

Conditions

Esophagogastric Adenocarcinoma; Metastatic Disease; No Previous Chemotherapy for Metastatic Esophagogastric Cancer

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival

  30 months from first patient in

Secondary Outcomes (4)

• Overall Survival (OS)

  5 years from first patient in

• Objective Response Rate (ORR, according to RECIST v1.1)

  30 months from first patient in

• Safety and tolerability (adverse event assessment according to CTCAE v 4.0)

  30 months from first patient in

• Quality of Life evaluated by questionnaires

  30 months from first patient in

Study Arms (2)

mFOLFOX6 + Nintedanib

ACTIVE COMPARATOR

Patients will receive nintedanib in combination with mFOLFOX6 (5-Fluorouracil 400 mg/m2 bolus on day 1, 5-Fluorouracil 2400 mg/m2 continuous infusion over 46 hours starting on day 1, Leucovorin 400 mg/m2 on day 1, Oxaliplatin 85 mg/m2 on day 1) via IV infusions every 2 weeks (14 days). Dose modification of nintedanib and mFOLFOX6 is allowed. Patients may continue to receive protocol therapy as long as they have not experienced any adverse events requiring permanent discontinuation of study medication and have not demonstrated disease progression.

Drug: Nintedanib; Drug: Fluorouracil; Drug: Leucovorin; Drug: Oxaliplatin

mFOLFOX6 + Placebo

PLACEBO COMPARATOR

Patients will receive placebo in combination with mFOLFOX6 (5-Fluorouracil 400 mg/m2 bolus on day 1, 5-Fluorouracil 2400 mg/m2 continuous infusion over 46 hours starting on day 1, Leucovorin 400 mg/m2 on day 1, Oxaliplatin 85 mg/m2 on day 1) via IV infusions every 2 weeks (14 days). Dose modification of placebo and mFOLFOX6 is allowed. Patients may continue to receive protocol therapy as long as they have not experienced any adverse events requiring permanent discontinuation of study medication and have not demonstrated disease progression.

Drug: Fluorouracil; Drug: Leucovorin; Drug: Oxaliplatin; Drug: Placebo

Interventions

Nintedanib DRUG

mFOLFOX6 + Nintedanib

Fluorouracil DRUG

mFOLFOX6 + Nintedanib; mFOLFOX6 + Placebo

Leucovorin DRUG

mFOLFOX6 + Nintedanib; mFOLFOX6 + Placebo

Oxaliplatin DRUG

mFOLFOX6 + Nintedanib; mFOLFOX6 + Placebo

Placebo DRUG

mFOLFOX6 + Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed esophagogastric adenocarcinoma with metastatic (M1) disease
• HER2-negative tumors as per local assessment (according to Rüschoff-Criteria)
• Presence of at least one evaluable lesion per RECIST v1.1
• Representative formalin fixed, paraffin embedded tumor blocks or unstained tissue slides, either from the primary tumor or a metastatic lesion, must be available for histological central review of FGFR2 and associated oncogenic pathway and tumor stroma analyses
• Age 18 years or older
• ECOG performance status 0-1
• Within 7 days prior to treatment start: adequate bone marrow, liver and renal function and coagulation parameters:
• Neutrophils ≥ 1.5 x 109/L
• Hemoglobin ≥ 9 g/dL (or ≥ 5.6 mmol/L). Blood transfusions or the administration of hematopoietic growth factors are allowed to achieve these baseline values
• Platelets ≥ 100 x 109/L. Platelet transfusions or the administration of hematopoietic growth factors are allowed to achieve these baseline values
• Bilirubin ≤ 1.5 x ULN
• Patients with Gilbert syndrome and/or bilirubin \<2 ULN and normal AST/ALT are eligible
• SGPT/ALT and SGOT/AST ≤ 2.5 x ULN for patients with liver metastasis
• SGPT/ALT and SGOT/ AST ≤ 1.5x ULN for patients without liver metastasis
• Serum creatinine ≤ 1.5 x ULN or creatinine clearance/eGFR \> 45 ml/min assessed as per local standard method

You may not qualify if:

• History or clinical evidence of central nervous system metastasis or leptomeningeal tumor spread.
• Other malignant disease in the previous 5 years (apart from basal-cell cancer of the skin or pre-invasive cervical cancer).
• Other anti-cancer therapy (systemic therapy, radiotherapy, surgery) within 28 days prior to treatment start and while on protocol treatment.
• Treatment with another investigational agent within 28 days prior to treatment start and while on protocol treatment.
• Chronic diarrhea or short bowel syndrome
• Legal incapacity or limited legal capacity
• Known hypersensitivity to nintedanib
• Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration/randomization in the trial.

Sponsors & Collaborators

• European Organisation for Research and Treatment of Cancer - EORTC: lead

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

nintedanib; Fluorouracil; Leucovorin; Oxaliplatin

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Coordination Complexes; Organic Chemicals

Study Officials

• Maren Knoedler

  Universitaetsklinikum Leipzig, Germany

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 28, 2016
• First Posted: August 5, 2016
• Study Start: December 1, 2016
• Primary Completion: June 1, 2019
• Last Updated: May 9, 2017

Record last verified: 2017-05