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 (MEGA)

November 13, 2020 updated by: UNICANCER

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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)

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
162

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Villejuif, France, 94805
        • Institut Gustave Roussy

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • Rilotumumab

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Progression-free survival at 4 months
Time Frame: 4 months
based on the proportion of success in each patient group (patient without progression at 4 months)
4 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Progression-free survival
Time Frame: until progression or death
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.
until progression or death
Overall survival
Time Frame: until death
Overall survival is defined as the time from randomization to death any cause or last follow-up news (censored data).
until death
Time to progression
Time Frame: 4 months
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.
4 months
Objective tumor response rate (OR) (= complete responses [CR] + partial responses [PR]) according to RECIST V1.1
Time Frame: until progression
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.
until progression
Objective response duration
Time Frame: until progression
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.
until progression
Disease control rate (Complete Response + Partial Response + stable disease [SD])
Time Frame: 4 months
The tumor control rate is rate of objective responses (complete responses and partial responses) and stable disease responses.
4 months
Tolerance of the treatment
Time Frame: 24 months
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)).
24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
UNICANCER

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • 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 François 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: 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: 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 Salpetriere
  • 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, Hôpital Haut Lévêque
  • Principal Investigator: Pascal ARTRU, Dr, Hopital Prive 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

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2011

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 1, 2014

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 1, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 11, 2011

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 28, 2011

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 29, 2011

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 17, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 13, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • PRODIGE 17 / ACCORD 20/0904
  • 2009-012797-12 (EUDRACT_NUMBER)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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