Clinical trial NCT01443065: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Malignant Neoplasm of Esophagus
Malignant Neoplasm of Stomach
Keywords: Adenocarcinoma
Locally advanced (non operable) or metastatic
First line treatment
Lead sponsor: UNICANCER
Sponsor class: OTHER
First posted: 2011-09-29
Enrollment: 162
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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 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.

Primary outcomes:
measure: Progression-free survival at 4 months
timeFrame: 4 months
Secondary outcomes:
measure: Progression-free survival
timeFrame: until progression or death
measure: Overall survival
timeFrame: until death
measure: Time to progression
timeFrame: 4 months
measure: Objective tumor response rate (OR) (= complete responses [CR] + partial responses [PR]) according to RECIST V1.1
timeFrame: until progression
measure: Objective response duration
timeFrame: until progression
measure: Disease control rate (Complete Response + Partial Response + stable disease [SD])
timeFrame: 4 months
measure: Tolerance of the treatment
timeFrame: 24 months
Other outcomes:
Locations:
city: Villejuif
country: France
facility: Institut Gustave Roussy
Study officials:
affiliation: Gustave Roussy, Cancer Campus, Grand Paris
name: David MALKA, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre Antoine Lacassagne-NICE
name: Eric FRANCOIS, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: Institut Curie Paris
name: Bruno BUECHER, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: Hôpital Andre Boulloche-MONTBELIARD
name: Christophe BORG, Pr
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre Val d'Aurelle Paul Lamarque-MONTPELLIER
name: Emmanuelle SAMALIN, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre Paul Papin-ANGERS
name: You Heng LAM, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre Georges Francois Leclerc-DIJON
name: François GHIRINGHELLI, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre Hospitalier Lyon Sud-PIERRE BENITE
name: Driffa MOUSSATA, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre Francois Baclesse-CAEN
name: Marie-Pierre GALAIS, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre René Huguenin-SAINT-CLOUD
name: Frédérique CVITKOVIC, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre Alexis Vautrin-VANDOEUVRE LES NANCY
name: Marie-Claire KAMINSKY, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: Hôpital Robert Debré - REIMS
name: Olivier BOUCHE, Pr
role: PRINCIPAL_INVESTIGATOR
affiliation: Hôpital Européen Georges Pompidou-PARIS (HEGP)
name: Julien TAIEB, Pr
role: PRINCIPAL_INVESTIGATOR
affiliation: Polyclinique Bordeaux Nord Aquitaine-BORDEAUX
name: Cédric LECAILLE, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: Institut Bergonié Bordeaux
name: Yves BECOUARN, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre Hospitalier La Source-ORLEANS
name: Barbara DAUVOIS, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: Hôpital Edouard Herriot-LYON
name: Julien FORESTIER, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre René Gauducheau
name: Jaafar BENNOUNA, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre Leon Berard
name: Christelle DE LA FOUCHARDIERE, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre Hospitalier Jean Minjoz
name: Christophe BORG, Pr
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre Hospitalier La Pitié Salpétrière
name: Jean Baptiste BACHET, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: Institut Paoli-Calmettes
name: Jean Luc RAOUL, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: Hôpital Saint Antoine
name: Leila BENGRINE LEFEVRE, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: CHP Saint Grégoire
name: Laurent MIGLIANICO, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre Hospitalier La Timone
name: Laetitia DAHAN, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: Hôpital Avicenne
name: Thomas APARICIO, Pr
role: PRINCIPAL_INVESTIGATOR
affiliation: Hôpital Saint Joseph
name: Hervé PERRIER, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: CHU Morvan
name: Jean Philippe METGES, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: Hôpîtal haut Lévèque
name: Eric TERREBONNE, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: Hôpital Privé Jean Mermoz
name: Pascal ARTRU, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: Groupe Hospitalier Saint Joseph
name: Gaël DEPLANQUE, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: CHR Annecy
name: Emmanuel MAILLARD, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre Oscar Lambret
name: Antoine ADENIS, Pr
role: PRINCIPAL_INVESTIGATOR
References: