ARTemIS-Eso is a phase I-II, three-level, open-label trial with a dose-expansion cohort at recommended schedule in both esophageal cancer histological groups (squamous cell carcinoma and adenocarcinoma) of RCT and ImT administered prior to surgery.
This study is indicated to patients with adenocarcinomas of the esophagus or gastro-esophageal junction and squamous cell carcinoma of the esophagus. The study consists of 2 parts: Phase I of the study is composed of the 3 following levels, corresponding to changes in the schedule and the number of administrations of monalizumab: Level 1: monalizumab (ImT) administration starts 2 weeks after the end of RCT (Total of 3 ImT doses). A maximum of 7 days delay is allowed. Level 2: monalizumab administration starts directly at the end of RCT (Total of 4 ImT doses). The first dose of monalizumab should be given on the following working day after the last radiotherapy administration. Level 3: monalizumab administration starts 2 weeks after the start of RCT (total of 6 ImT doses). A maximum of 7 days delay is allowed. Phase II (Expansion cohort): At the recommended level determined in phase I and according to the number of patients already accrued, approximately 48-51 additional patients (half-SCC and half-ADC) are included with the aim of assessing the activity of the recommended combination.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Monalizumab (IPH2201) is given at the recommended dose of 10 mg/kg, intravenously (infusion during 60 minutes) every two weeks
A total of 4 cycles of FOLFOX is administrated every 2 weeks with one cycle 15 days prior to the radiotherapy and 3 cycles during the radiotherapy whatever the level
A total of 4 cycles of FOLFOX is administrated every 2 weeks with one cycle 15 days prior to the radiotherapy and 3 cycles during the radiotherapy whatever the level
Institut Jules Bordet
Brussels, Belgium
Phase I: determine the feasibility to administer monalizumab
Successful and safe administration of the combination of radio-chemotherapy and at least 2 doses of immunotherapy
Time frame: From date of randomization until the date of first documented disease recurrence, assessed up to 28 months
Phase II: pCR rate
Defined by the absence of any tumoral cells on the surgical specimen post esophagectomy
Time frame: At date of surgery, assessed at 16 weeks post randomization
Phase I: pCR rate
Defined by the absence of any tumoral cells on the surgical specimen post esophagectomy
Time frame: At date of surgery, assessed at 16 weeks post randomization
Phase I: DFS and OS at 2 years after surgery
DFS and OS at 2 years after surgery
Time frame: From date of randomization until the date of first documented event, assessed up to 28 months
Phase I: Human Anti-Human Antibodies against monalizumab (HAHA) in serum
Human Anti-Human Antibodies against monalizumab (HAHA) in serum
Time frame: Week 5 to 3 months post surgery
Phase II: Two year-disease free survival (DFS) and two year-overall survival (OS)
Two year-disease free survival (DFS) and two year-overall survival (OS)
Time frame: 2 years after the date the last patient had his surgery provided the trial objectives have been met
Phase II: Toxicity profile according to CTCAE v.4.03
Toxicity profile according to CTCAE v.4.03
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Radiation therapy must start the first day of FOLFOX chemotherapy. Radiation is given once daily for 5 consecutive days; on the days that the patient receives chemotherapy (and monalizumab when applicable), chemotherapy (and monalizumab) should be given prior to radiotherapy.
18-FDG-PET scan will be performed just before the beginning of radio-chemotherapy (D10-D14) and will be blinded for investigators and patients. Another 18-FDG-PET will be performed before surgery (surgery Day-5 to surgery Day -1) to exclude metastatic evolution
Surgery is performed preferably 8 weeks after the completion of the radio-chemotherapy, and it should not be performed less than one week after the last dose of monalizumab
Time frame: From date of randomization until the date of first documented event, assessed up to 28 months
Phase II: Metabolic response after 1 course of CT and before surgery
Metabolic response after 1 course of CT and before surgery
Time frame: from week 1 up to the time of surgery
Phase II: Number of the tumour-infiltrating lymphocytes (TILs)
Number of the tumour-infiltrating lymphocytes (TILs)
Time frame: at baseline, after 1 course of CT at week 3 and after surgery at 16 weeks