MEGA (Met or EGFR Inhibition in Gastroesophageal Adenocarcinoma): FOLFOX Alone or in Combination With AMG 102 or Panitumumab as First-line Treatment in Patients With Advanced Gastroesophageal Adenocarcinoma

This study is currently recruiting participants.
Verified March 2013 by UNICANCER
Sponsor:
Information provided by (Responsible Party):
UNICANCER
ClinicalTrials.gov Identifier:
NCT01443065
First received: August 11, 2011
Last updated: March 5, 2013
Last verified: March 2013
  Purpose

This multicentre, open-label, randomized phase II trial is ongoing in 30 centres in France. Main eligibility criteria include: histologically proven adenocarcinoma of the stomach, esophagus or gastroesophageal junction; locally advanced or metastatic disease; measurable disease (RECIST 1.1); no known HER2 overexpression; no prior palliative chemotherapy.


Condition Intervention Phase
Malignant Neoplasm of Esophagus
Malignant Neoplasm of Stomach
Drug: Oxaliplatin
Drug: Folinic Acid
Drug: 5-fluoro-uracil
Drug: panitumumab
Drug: AMG102
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: MEGA (Met or EGFR Inhibition in Gastroesophageal Adenocarcinoma): FOLFOX Alone or in Combination With AMG 102 or Panitumumab as First-line Treatment in Patients With Advanced Gastroesophageal Adenocarcinoma FNCLCC-FFCD-AGEO PRODIGE 17-ACCORD 20 Randomized Phase II Trial

Resource links provided by NLM:


Further study details as provided by UNICANCER:

Primary Outcome Measures:
  • Progression-free survival at 4 months [ Time Frame: 4 months ] [ Designated as safety issue: Yes ]
    based on the proportion of success in each patient group (patient without progression at 4 months)


Secondary Outcome Measures:
  • Progression-free survival [ Time Frame: until progression or death ] [ Designated as safety issue: Yes ]
    Progression-free survival is defined as the time from randomization to progression (RECIST v1.1 criteria) or death. Patients alive without progression will be censored at the last tumoral evaluation and 5 years maximum.

  • Overall survival [ Time Frame: until death ] [ Designated as safety issue: Yes ]
    Overall survival is defined as the time from randomization to death any cause or last follow-up news (censored data).

  • Time to progression [ Time Frame: 4 months ] [ Designated as safety issue: Yes ]
    Time to progression is defined as the time from randomization to progression (RECIST v1.1 criteria). Patients alive without progression will be censored at the last tumoral evaluation. Patients died without progression will be censored at the death date any cause.

  • Objective tumor response rate (OR) (= complete responses [CR] + partial responses [PR]) according to RECIST V1.1 [ Time Frame: until progression ] [ Designated as safety issue: Yes ]
    The objective tumor response will be evaluated by the investigator with RECIST v1.1 criteria every 8 (± 1) weeks up to disease progression. Patients with symptoms suggestive of disease progression will have a tumoral evaluation when symptoms will occur.

  • Objective response duration [ Time Frame: until progression ] [ Designated as safety issue: Yes ]
    The Objective response duration is defined as time from first Complete Response or Partial Response to progression. Patients died without progression will be censored at death date.

  • Disease control rate (Complete Response + Partial Response + stable disease [SD]) [ Time Frame: 4 months ] [ Designated as safety issue: Yes ]
    The tumor control rate is rate of objective responses (complete responses and partial responses) and stable disease responses.

  • Tolerance of the treatment [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
    Tolerability of the treatment will be based on toxicities of evaluated products by clinical and biological measurements (NCIC/CTC (CTCAE V4) criteria, except for peripheral neuropathy toxicity (Lévi scale)).


Estimated Enrollment: 165
Study Start Date: January 2011
Estimated Study Completion Date: January 2019
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm A : simplified Folfox 4

Every 2 weeks :

  • Oxaliplatin : 85 mg/m2 over 120 mn (2h) IV on D1
  • Folinic acid : 400 mg/m² (racemic form) (or 200 mg/m² if L-folinic acid) over 2 h IV on D1 followed by :
  • 5-fluoro-uracil : 400 mg/m² in IV bolus on D1 followed by :
  • 5-fluoro-uracil : 2400 mg/m² in IV infusion over 46 h
Drug: Oxaliplatin
85mg/m² over 120 mn every 2 weeks up to progression or toxicity
Other Name: Eloxatine
Drug: Folinic Acid
400mg/m² over 120 mn every 2 weeks up to progression or toxicity
Drug: 5-fluoro-uracil
400mg/m² in bolus, then 2400mg/m² over 46 h every 2 weeks up to progression or toxicity
Experimental: Arm B : simplified FOLFOX 4 + panitumumab

Every 2 weeks :

  • Oxaliplatin : 85 mg/m2 over 120 mn IV on D1
  • Folinic acid : 400 mg/m² (racemic form) (or 200 mg/m² with L-folinic acid) over 2 h IV on D1 (in Y to oxaliplatin) followed by :
  • 5-fluoro-uracil : 400 mg/m², IV bolus on D1, followed by :
  • 5-fluoro-uracil : 2400 mg/m², IV infusion IV over 46 h
  • Panitumumab : 6 mg/kg de 60 à 90 mn ± 15 mn IV every 14 days, just before chemotherapy administration (oxaliplatin and folinic acid), on Day 1 of each cycle. If the 1st infusion of panitumumab is well tolerated, the next infusions can be administered over 30 ± 10 mn.
Drug: Oxaliplatin
85mg/m² over 120 mn every 2 weeks up to progression or toxicity
Other Name: Eloxatine
Drug: Folinic Acid
400mg/m² over 120 mn every 2 weeks up to progression or toxicity
Drug: 5-fluoro-uracil
400mg/m² in bolus, then 2400mg/m² over 46 h every 2 weeks up to progression or toxicity
Drug: panitumumab
6mg/kg over 60-90 mn every 2 weeks up to progression or toxicity
Other Name: Vectibix
Experimental: Arm C : simplified FOLFOX 4 + AMG 102

Every 2 weeks :

  • Oxaliplatin : 85 mg/m2 over 120 mn IV on D1
  • Folinic Acid : 400 mg/m² (racemic) (or 200 mg/m² with L-folinic acid) over 2 h IV on D1 (in Y/concomitant with oxaliplatin) followed by :
  • 5-fluoro-uracil : 400 mg/m² IV bolus on D1 followed by :
  • 5-fluoro-uracil : 2400 mg/m² in IV perfusion over 46 h
  • AMG 102 : 10 mg/kg over 60 ± 15 mn IV every 14 days, just before chemotherapy administration (oxaliplatin and folinic acid), on Day 1 of each cycle. If the first infusion is well tolerated (without severe infusion-related reactions), the following infusions can be administered over 30 ± 10 mn.
Drug: Oxaliplatin
85mg/m² over 120 mn every 2 weeks up to progression or toxicity
Other Name: Eloxatine
Drug: Folinic Acid
400mg/m² over 120 mn every 2 weeks up to progression or toxicity
Drug: 5-fluoro-uracil
400mg/m² in bolus, then 2400mg/m² over 46 h every 2 weeks up to progression or toxicity
Drug: AMG102
10mg/kg over 60 mn every 2 weeks up to progression or toxicity
Other Name: Rilotumumab

Detailed Description:

Patients are randomised to modified FOLFOX6 (oxaliplatin 85 mg/m2, FA 400 mg/m², FU 400 mg/m² bolus then 2400 mg/m² over 46 hr) alone or combined to either panitumumab (6 mg/kg) or AMG 102 (10 mg/kg), every two weeks until unacceptable toxicity or disease progression. Judgment criteria include 4-month progression-free survival (PFS) rate (primary endpoint), OS, objective response rate, and safety. Ancillary studies aim to identify candidate predictive and prognostic biomarkers among functional of molecular alterations of the EGFR/RAS/RAF and HGF/c-Met pathways, and to monitor circulating tumour cells and circulating immune cells (myeloid derived suppressor cells, NK cells) in sequential blood samples taken at baseline and through the study treatment. A total of 165 pts will be enrolled (Fleming's one-step design)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically proven adenocarcinoma of the stomach, the esophagus or the cardia (with or without signet ring cells; intestinal, diffuse or mixed form).
  • Locally advanced (non resectable) or metastatic disease.
  • Measurable disease (at least one measurable tumor) according to the RECIST V1.1 criteria (the tumor should not be located in a previous field of radiation).
  • Absence of previous palliative chemotherapy. Previous neo-adjuvant or adjuvant chemotherapies (alone or combinated with radiotherapy) are authorized, including biotherapy (except anti-EGFR or anti-c-Met / HGF), if it has been stopped at least 12 months before inclusion.
  • Previous radiotherapy authorized if stopped at least 14 days before randomization and if at least one measurable target outside the radiation area is present.
  • No major surgery ≤ 28 days, or minor surgery ≤ 14 days, prior to randomization
  • Sites of disease evaluated within 28 days prior to randomization with thoracic-abdominal-pelvic CT scan (or abdominal-pelvic MRI plus Chest X-ray).
  • Age ≥ 18 years.
  • Patient general status : ECOG 0-1.
  • Life expectancy ≥ 3 months.
  • Hemoglobin > or = 9 g/L - (transfusion authorized if necessary), PNN ≥ 1,5.109/l, platelets ≥ 100.109/l.
  • Hepatic transaminases ≤ 2.5 times upper limit of normal (ULN) (≤ 5 ULN in case of hepatic metastases), alkaline phosphatase ≤ 2.5 ULN (≤ 5 ULN in case of hepatic metastases), total bilirubinemia ≤ 1.5 ULN)
  • Creatinine clearance (calculated or measured) ≥ 50 ml / min, serum creatinine > 1.5 ULN
  • Prothrombin time (PT) ≥ 60 %, INR < 1,5 (except if anticoagulant therapy)
  • Magnesemia and calcemia ≥ Lower Limit of Normal (LLN)
  • Negative Pregnancy test for women of child-bearing age.
  • Information given to the patient and signed informed consent.
  • Public Health insurance coverage.
  • Sample of tumour (primitive or metastatic) available.

Exclusion Criteria:

  • Known brain or leptomeningeal metastases.
  • Positive HER2 Status (IHC 3+ or IHC2+/FISH or CISH+) .
  • contraindication, allergy or hypersensitivity to ANY OF the study treatments.
  • Prior Treatment with EGFR inhibitor or HGF / c-Met inhibitor.
  • Patient already included in another clinical trial testing an experimental drug.
  • Peripheral edema > grade 2.
  • Proteinuria > 1 g/24h
  • Clinically significant cardiovascular disease (such as unstable angina pectoris, severe congestive heart failure, uncontrolled severe cardiac arrhythmia) within 12 months prior to randomization.
  • Thrombosis or ischemic vascular event during the last 12 months (deep venous thrombosis, pulmonary embolism, STROKE or established cerebral infarction, myocardial infarction).
  • Medical history or signs of interstitial pneumopathy or pulmonary fibrosis.
  • Peripheral neuropathy > grade 1.
  • Clinically significant hemorrhage of the upper gastrointestinal tract (requiring blood transfusion or hemostatic interventional procedure.
  • Actively evolutive inflammatory bowel disease or any other intestinal disease causing chronic diarrhea (≥ grade 2).
  • Any uncontrolled concomitant disease (e.g., uncontrolled diabetes) or medical history (e.g., organ transplantation) which, according to the opinion of the investigator, may interfere with the interpretation of the study results.
  • Any comorbidity or situation which, according to the opinion of the investigator, could increase the risk of toxicity (e.g., Dihydropyrimidine dehydrogenase deficiency).
  • Chronic or active HIV, HBV or HCV infections.
  • Severe and\or not healed wound.
  • Any active infection requiring systemic treatment, or any uncontrolled infection within 14 days before randomization.
  • Other concomitant malignancy or history of cancer (except carcinoma in situ of the cervix, or non melanoma skin cancer, with curative intent treatment), except when considered in complete remission for at least 5 years before randomization.
  • Pregnant women or women who might become pregnant during the study (or who plan to become pregnant within 6 months after the last administration of a study drug) or lactating women.
  • Men or women who have the age of procreation and who do not abide with the use of a highly efficient contraceptive means (according to the current institutional standards) or, alternatively, the use of abstinence during the study treatment and until 6 months after last administration of the study drugs.
  • Patient unwilling to comply with the medical follow-up required by the trial because of geographic social or psychological reasons.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01443065

Contacts
Contact: Beata JUZYNA +33(1)44235567 b-juzyna@fnclcc.fr

Locations
France
Institut Gustave Roussy Recruiting
Villejuif, France, 94805
Contact: David MALKA, Dr    +33(1)42114289    malka@igr.fr   
Principal Investigator: David MALKA, Dr         
Sub-Investigator: Valérie BOIGE, Dr         
Sub-Investigator: Michel DUCREUX, Pr         
Sub-Investigator: Pascal BURTIN, Dr         
Sponsors and Collaborators
UNICANCER
Investigators
Principal Investigator: David MALKA, Dr Gustave Roussy, Cancer Campus, Grand Paris
Principal Investigator: Eric FRANCOIS, Dr Centre Antoine Lacassagne-NICE
Principal Investigator: Bruno BUECHER, Dr Institut Curie-PARIS
Principal Investigator: Christophe BORG, Pr Hôpital Andre Boulloche-MONTBELIARD
Principal Investigator: Emmanuelle SAMALIN, Dr Centre Val d'Aurelle Paul Lamarque-MONTPELLIER
Principal Investigator: You Heng LAM, Dr Centre Paul Papin-ANGERS
Principal Investigator: François GHIRINGHELLI, Dr Centre Georges Francois Leclerc-DIJON
Principal Investigator: Driffa MOUSSATA, Dr Centre Hospitalier Lyon Sud-PIERRE BENITE
Principal Investigator: Marie-Pierre GALAIS, Dr Centre Francois Baclesse-CAEN
Principal Investigator: Frédérique CVITKOVIC, Dr Centre René Huguenin-SAINT-CLOUD
Principal Investigator: Marie-Claire KAMINSKY, Dr Centre Alexis Vautrin-VANDOEUVRE LES NANCY
Principal Investigator: Olivier BOUCHE, Pr Hôpital Robert Debré - REIMS
Principal Investigator: Julien TAIEB, Pr Hôpital Européen Georges Pompidou-PARIS (HEGP)
Principal Investigator: Cédric LECAILLE, Dr Polyclinique Bordeaux Nord Aquitaine-BORDEAUX
Principal Investigator: Yves BECOUARN, Dr Institut Bergonié-BORDEAUX
Principal Investigator: Barbara DAUVOIS, Dr Centre Hospitalier La Source-ORLEANS
Principal Investigator: Julien FORESTIER, Dr Hôpital Edouard Herriot-LYON
  More Information

No publications provided

Responsible Party: UNICANCER
ClinicalTrials.gov Identifier: NCT01443065     History of Changes
Other Study ID Numbers: PRODIGE 17 / ACCORD 20/0904
Study First Received: August 11, 2011
Last Updated: March 5, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by UNICANCER:
Adenocarcinoma
Locally advanced (non operable) or metastatic
First line treatment

Additional relevant MeSH terms:
Adenocarcinoma
Neoplasms
Esophageal Neoplasms
Stomach Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Stomach Diseases
Fluorouracil
Oxaliplatin
Antibodies, Monoclonal
Leucovorin
Folic Acid
Levoleucovorin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 17, 2014