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

NCT01443065 | Completed Phase 2 DMC

• 2 other identifiers: PRODIGE 17 / ACCORD 20/09042009-012797-12
• Study Type: interventional
• Target: 162
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Malignant Neoplasm of Esophagus; Malignant Neoplasm of Stomach

Keywords

Adenocarcinoma; Locally advanced (non operable) or metastatic; First line treatment

Outcome Measures

Primary Outcomes (1)

• Progression-free survival at 4 months

  based on the proportion of success in each patient group (patient without progression at 4 months)

  4 months

Secondary Outcomes (7)

• Progression-free survival

  until progression or death

• Overall survival

  until death

• Time to progression

  4 months

• Objective tumor response rate (OR) (= complete responses [CR] + partial responses [PR]) according to RECIST V1.1

  until progression

• Objective response duration

  until progression

Study Arms (3)

Arm A : simplified Folfox 4

ACTIVE COMPARATOR

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; Drug: Folinic Acid; Drug: 5-fluoro-uracil

Arm B : simplified FOLFOX 4 + panitumumab

EXPERIMENTAL

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; Drug: Folinic Acid; Drug: 5-fluoro-uracil; Drug: panitumumab

Arm C : simplified FOLFOX 4 + AMG 102

EXPERIMENTAL

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; Drug: Folinic Acid; Drug: 5-fluoro-uracil; Drug: AMG102

Interventions

Oxaliplatin DRUG

85mg/m² over 120 mn every 2 weeks up to progression or toxicity

Also known as: Eloxatine

Arm A : simplified Folfox 4; Arm B : simplified FOLFOX 4 + panitumumab; Arm C : simplified FOLFOX 4 + AMG 102

Folinic Acid DRUG

400mg/m² over 120 mn every 2 weeks up to progression or toxicity

Arm A : simplified Folfox 4; Arm B : simplified FOLFOX 4 + panitumumab; Arm C : simplified FOLFOX 4 + AMG 102

5-fluoro-uracil DRUG

400mg/m² in bolus, then 2400mg/m² over 46 h every 2 weeks up to progression or toxicity

Arm A : simplified Folfox 4; Arm B : simplified FOLFOX 4 + panitumumab; Arm C : simplified FOLFOX 4 + AMG 102

panitumumab DRUG

6mg/kg over 60-90 mn every 2 weeks up to progression or toxicity

Also known as: Vectibix

Arm B : simplified FOLFOX 4 + panitumumab

AMG102 DRUG

10mg/kg over 60 mn every 2 weeks up to progression or toxicity

Also known as: Rilotumumab

Arm C : simplified FOLFOX 4 + AMG 102

Eligibility Criteria

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

You may qualify if:

• 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).
• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• UNICANCER: lead

Study Sites (1)

Institut Gustave Roussy

Villejuif, 94805, France

Location

MeSH Terms

Conditions

Esophageal Neoplasms; Stomach Neoplasms; Adenocarcinoma

Interventions

Oxaliplatin; Leucovorin; Panitumumab; rilotumumab

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Stomach Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

• Jaafar BENNOUNA, Dr

  Centre René Gauducheau

  PRINCIPAL INVESTIGATOR

• Christelle DE LA FOUCHARDIERE, Dr

  Centre Leon Berard

  PRINCIPAL INVESTIGATOR

• Christophe BORG, Pr

  Centre Hospitalier Jean Minjoz

  PRINCIPAL INVESTIGATOR

• Jean Baptiste BACHET, Dr

  Centre Hospitalier La Pitié Salpétrière

  PRINCIPAL INVESTIGATOR

• Jean Luc RAOUL, Dr

  Institut Paoli-Calmettes

  PRINCIPAL INVESTIGATOR

• Leila BENGRINE LEFEVRE, Dr

  Hôpital Saint Antoine

  PRINCIPAL INVESTIGATOR

• Laurent MIGLIANICO, Dr

  CHP Saint Grégoire

  PRINCIPAL INVESTIGATOR

• Laetitia DAHAN, Dr

  Centre Hospitalier La Timone

  PRINCIPAL INVESTIGATOR

• Thomas APARICIO, Pr

  Hôpital Avicenne

  PRINCIPAL INVESTIGATOR

• Hervé PERRIER, Dr

  Hôpital Saint Joseph

  PRINCIPAL INVESTIGATOR

• Jean Philippe METGES, Dr

  CHU Morvan

  PRINCIPAL INVESTIGATOR

• Eric TERREBONNE, Dr

  Hôpîtal haut Lévèque

  PRINCIPAL INVESTIGATOR

• Pascal ARTRU, Dr

  Hôpital Privé Jean Mermoz

  PRINCIPAL INVESTIGATOR

• Gaël DEPLANQUE, Dr

  Groupe Hospitalier Saint Joseph

  PRINCIPAL INVESTIGATOR

• Emmanuel MAILLARD, Dr

  CHR Annecy

  PRINCIPAL INVESTIGATOR

• Antoine ADENIS, Pr

  Centre Oscar Lambret

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 11, 2011
• First Posted: September 29, 2011
• Study Start: January 1, 2011
• Primary Completion: March 1, 2014
• Study Completion: September 1, 2018
• Last Updated: November 17, 2020

Record last verified: 2020-11

Locations

FR (1)