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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

NCT ID: NCT01443065

Last Updated: 2020-11-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

162 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-01-31

Study Completion Date

2018-09-30

Brief Summary

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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.

Detailed Description

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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)

Conditions

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Malignant Neoplasm of Esophagus Malignant Neoplasm of Stomach

Keywords

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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

Group Type ACTIVE_COMPARATOR

Oxaliplatin

Intervention Type DRUG

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

Folinic Acid

Intervention Type DRUG

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

5-fluoro-uracil

Intervention Type DRUG

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

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.

Group Type EXPERIMENTAL

Oxaliplatin

Intervention Type DRUG

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

Folinic Acid

Intervention Type DRUG

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

5-fluoro-uracil

Intervention Type DRUG

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

panitumumab

Intervention Type DRUG

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

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.

Group Type EXPERIMENTAL

Oxaliplatin

Intervention Type DRUG

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

Folinic Acid

Intervention Type DRUG

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

5-fluoro-uracil

Intervention Type DRUG

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

AMG102

Intervention Type DRUG

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

Interventions

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Oxaliplatin

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

Intervention Type DRUG

Folinic Acid

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

Intervention Type DRUG

5-fluoro-uracil

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

Intervention Type DRUG

panitumumab

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

Intervention Type DRUG

AMG102

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

Intervention Type DRUG

Other Intervention Names

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Eloxatine Vectibix Rilotumumab

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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UNICANCER

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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David MALKA, Dr

Role: PRINCIPAL_INVESTIGATOR

Gustave Roussy, Cancer Campus, Grand Paris

Eric FRANCOIS, Dr

Role: PRINCIPAL_INVESTIGATOR

Centre Antoine Lacassagne, Nice

Bruno BUECHER, Dr

Role: PRINCIPAL_INVESTIGATOR

Institut Curie Paris

Christophe BORG, Pr

Role: PRINCIPAL_INVESTIGATOR

Hôpital Andre Boulloche-MONTBELIARD

Emmanuelle SAMALIN, Dr

Role: PRINCIPAL_INVESTIGATOR

Centre Val d'Aurelle Paul Lamarque-MONTPELLIER

You Heng LAM, Dr

Role: PRINCIPAL_INVESTIGATOR

Centre Paul Papin-ANGERS

François GHIRINGHELLI, Dr

Role: PRINCIPAL_INVESTIGATOR

Centre Georges Francois Leclerc-DIJON

Driffa MOUSSATA, Dr

Role: PRINCIPAL_INVESTIGATOR

Centre Hospitalier Lyon Sud-PIERRE BENITE

Marie-Pierre GALAIS, Dr

Role: PRINCIPAL_INVESTIGATOR

Centre Francois Baclesse-CAEN

Frédérique CVITKOVIC, Dr

Role: PRINCIPAL_INVESTIGATOR

Centre René Huguenin-SAINT-CLOUD

Marie-Claire KAMINSKY, Dr

Role: PRINCIPAL_INVESTIGATOR

Centre Alexis Vautrin-VANDOEUVRE LES NANCY

Olivier BOUCHE, Pr

Role: PRINCIPAL_INVESTIGATOR

Hôpital Robert Debré - REIMS

Julien TAIEB, Pr

Role: PRINCIPAL_INVESTIGATOR

Hôpital Européen Georges Pompidou-PARIS (HEGP)

Cédric LECAILLE, Dr

Role: PRINCIPAL_INVESTIGATOR

Polyclinique Bordeaux Nord Aquitaine-BORDEAUX

Yves BECOUARN, Dr

Role: PRINCIPAL_INVESTIGATOR

Institut Bergonié Bordeaux

Barbara DAUVOIS, Dr

Role: PRINCIPAL_INVESTIGATOR

Centre Hospitalier La Source-ORLEANS

Julien FORESTIER, Dr

Role: PRINCIPAL_INVESTIGATOR

Hôpital Edouard Herriot-LYON

Jaafar BENNOUNA, Dr

Role: PRINCIPAL_INVESTIGATOR

Centre René Gauducheau

Christelle DE LA FOUCHARDIERE, Dr

Role: PRINCIPAL_INVESTIGATOR

Centre Leon Berard

Christophe BORG, Pr

Role: PRINCIPAL_INVESTIGATOR

Centre Hospitalier Jean Minjoz

Jean Baptiste BACHET, Dr

Role: PRINCIPAL_INVESTIGATOR

Centre Hospitalier La Pitié Salpétrière

Jean Luc RAOUL, Dr

Role: PRINCIPAL_INVESTIGATOR

Institut Paoli-Calmettes

Leila BENGRINE LEFEVRE, Dr

Role: PRINCIPAL_INVESTIGATOR

Hôpital Saint Antoine

Laurent MIGLIANICO, Dr

Role: PRINCIPAL_INVESTIGATOR

CHP Saint Grégoire

Laetitia DAHAN, Dr

Role: PRINCIPAL_INVESTIGATOR

Centre Hospitalier La Timone

Thomas APARICIO, Pr

Role: PRINCIPAL_INVESTIGATOR

Hôpital Avicenne

Hervé PERRIER, Dr

Role: PRINCIPAL_INVESTIGATOR

Hôpital Saint Joseph

Jean Philippe METGES, Dr

Role: PRINCIPAL_INVESTIGATOR

CHU Morvan

Eric TERREBONNE, Dr

Role: PRINCIPAL_INVESTIGATOR

Hôpîtal haut Lévèque

Pascal ARTRU, Dr

Role: PRINCIPAL_INVESTIGATOR

Hôpital Privé Jean Mermoz

Gaël DEPLANQUE, Dr

Role: PRINCIPAL_INVESTIGATOR

Groupe Hospitalier Saint Joseph

Emmanuel MAILLARD, Dr

Role: PRINCIPAL_INVESTIGATOR

CHR Annecy

Antoine ADENIS, Pr

Role: PRINCIPAL_INVESTIGATOR

Centre Oscar Lambret

Locations

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Institut Gustave Roussy

Villejuif, , France

Site Status

Countries

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France

Other Identifiers

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2009-012797-12

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

PRODIGE 17 / ACCORD 20/0904

Identifier Type: -

Identifier Source: org_study_id