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.
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
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
162
85mg/m² over 120 mn every 2 weeks up to progression or toxicity
400mg/m² over 120 mn every 2 weeks up to progression or toxicity
400mg/m² in bolus, then 2400mg/m² over 46 h every 2 weeks up to progression or toxicity
6mg/kg over 60-90 mn every 2 weeks up to progression or toxicity
10mg/kg over 60 mn every 2 weeks up to progression or toxicity
Institut Gustave Roussy
Villejuif, France
Progression-free survival at 4 months
based on the proportion of success in each patient group (patient without progression at 4 months)
Time frame: 4 months
Progression-free survival
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.
Time frame: until progression or death
Overall survival
Overall survival is defined as the time from randomization to death any cause or last follow-up news (censored data).
Time frame: until death
Time to progression
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.
Time frame: 4 months
Objective tumor response rate (OR) (= complete responses [CR] + partial responses [PR]) according to RECIST V1.1
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.
Time frame: until progression
Objective response duration
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.
Time frame: until progression
Disease control rate (Complete Response + Partial Response + stable disease [SD])
The tumor control rate is rate of objective responses (complete responses and partial responses) and stable disease responses.
Time frame: 4 months
Tolerance of the treatment
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)).
Time frame: 24 months
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