A Trial Assessing Several Schedules of Oral S-1 in Combination With a Fixed Dose of Oxaliplatin and Irinotecan
Phase 1
Completed
- Conditions
- Digestive Cancer
- Interventions
- Registration Number
- NCT02387138
- Lead Sponsor
- Institut du Cancer de Montpellier - Val d'Aurelle
- Brief Summary
This study is to determine the Maximal Tolerated Dose (MTD), the Dose Limitant Toxicities (DLTs) and the safety profile of S-1 combined with fixed doses of Irinotecan (SIRI schedule) and fixed doses of Irinotecan and Oxaliplatin (SIRINOX schedule).
- Detailed Description
Given the therapeutic potential and reduced toxicity advantages of S-1 compared with other fluoropyrimidines, this trial assessing S-1 with Oxaliplatin plus Irinotecan is warranted for future investigations (Phase II-III). The primary objectives are to determine the Maximal Tolerated Dose (MTD), the Dose Limitant Toxicities (DLTs) and the safety profile of S-1 combined with fixed doses of Irinotecan (SIRI schedule) and fixed doses of Irinotecan and Oxaliplatin (SIRINOX schedule).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 24
Inclusion Criteria
- Male or female ≥ 18 years old
- Histologically confirmed diagnosis of advanced or metastatic digestive adenocarcinoma (gastroesophageal adenocarcinoma, colorectal adenocarcinoma, pancreatic adenocarcinoma, cholangiocarcinoma, hepatocarcinoma)
- Metastatic or advanced disease not eligible for curative surgery
- No active biliary obstruction
- Previous adjuvant chemotherapy is allowed. It must be completed at least 6 months before the start of the study treatment
- First line chemotherapy is allowed (excluding chemotherapy with Capecitabine or 5 FU or Irinotecan or Oxaliplatin). Previous Oxaliplatin is allowed in patients receiving SIRI
- A four-week washout period since prior treatment
- One or more measurable metastatic lesions
- ECOG status ≤ 1
- Total bilirubin ≤ 1.5 Upper limit of normal (ULN), ALT or AST ≤ 2.5 ULN (or < 5 in case of liver impairment)
- Haemoglobin ≥ 10 g/dL, neutrophils ≥ 1,500/mm3, platelets ≥ 100,000/mm3 and white blood cells > 3000 /mm3
- Lipase < 1.5 ULN, serum creatinine ≤ 1.5 ULN
- Negative pregnancy test in women of childbearing potential
- Use of an effective contraceptive method during the whole treatment and up to 3 months after the completion of treatment
- Life expectancy > 3 months
- Informed consent form (ICF) signed prior to any study specific procedures
- Patients must be affiliated to a Social Security System
Exclusion Criteria
- History of previous treatment with Oxaliplatin except for SIRI, Irinotecan, 5 FU or Capecitabine as first-line chemotherapy
- Peripheral sensory neuropathy ≥ grade 2 at the time of signing the ICF
- Known central nervous system metastases
- Unique bone metastasis
- History or presence of other cancer within the past 5 years (except curatively treated non-melanoma skin cancer)
- Patients with a known deficiency of the enzyme dihydropyrimidine dehydrogenase (DPD), as well as patients who, within the previous four weeks, have been treated with a medicine that inhibits this enzyme
- Patients with rare hereditary problems of galactose intolerance, lactase deficiency or glucose or galactose malabsorption
- Malabsorption syndrome or disease significantly affecting gastro-intestinal function
- Patient with dysphagia or inability to swallow the tablets
- Inflammatory bowel disease with chronic diarrhoea (Grade ≥ 2 NCI CTC V4.03)
- History of organ transplantation with use of immunosuppression therapy
- Concomitant severe infection (> grade 2 NCI.CTCAE v4.03) or major organ failure
- Active cardiac disease, angina pectoris or myocardial infarction in the last 6 months
- Renal disease
- Unstable diabetes
- Creatinine clearance < 50 ml/min calculated using the MDRD formula
- Pregnant or breastfeeding women
- Participation in another clinical trial within 30 days prior to study entry
- Psychological, social, geographical or any other condition that would preclude study compliance (treatment administration and study follow-up)
- Legal incapacity or physical, psychological or mental status interfering with the patient's ability to sign the informed consent or to terminate the study
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description SIRINOX S-1 S-1: Administered orally twice daily from day 1 for 7 consecutive days followed by a 7-day recovery period in a 14-day cycle. The starting dose of S-1 will be two levels below the recommended dose defined in SIRI (20 mg/m² BID minimum) with a cohort dose escalation by 5 mg/m² increments (5 dose levels). Irinotecan : fixed dose of 180 mg/m² IV over 90 minutes on d1 of every cycle Oxaliplatin : fixed dose of 85 mg/m² over 120 minutes on d1 of every cycle G-csf : d8 to d13 systematically SIRINOX Irinotecan S-1: Administered orally twice daily from day 1 for 7 consecutive days followed by a 7-day recovery period in a 14-day cycle. The starting dose of S-1 will be two levels below the recommended dose defined in SIRI (20 mg/m² BID minimum) with a cohort dose escalation by 5 mg/m² increments (5 dose levels). Irinotecan : fixed dose of 180 mg/m² IV over 90 minutes on d1 of every cycle Oxaliplatin : fixed dose of 85 mg/m² over 120 minutes on d1 of every cycle G-csf : d8 to d13 systematically SIRINOX G-csf S-1: Administered orally twice daily from day 1 for 7 consecutive days followed by a 7-day recovery period in a 14-day cycle. The starting dose of S-1 will be two levels below the recommended dose defined in SIRI (20 mg/m² BID minimum) with a cohort dose escalation by 5 mg/m² increments (5 dose levels). Irinotecan : fixed dose of 180 mg/m² IV over 90 minutes on d1 of every cycle Oxaliplatin : fixed dose of 85 mg/m² over 120 minutes on d1 of every cycle G-csf : d8 to d13 systematically SIRINOX Oxaliplatin S-1: Administered orally twice daily from day 1 for 7 consecutive days followed by a 7-day recovery period in a 14-day cycle. The starting dose of S-1 will be two levels below the recommended dose defined in SIRI (20 mg/m² BID minimum) with a cohort dose escalation by 5 mg/m² increments (5 dose levels). Irinotecan : fixed dose of 180 mg/m² IV over 90 minutes on d1 of every cycle Oxaliplatin : fixed dose of 85 mg/m² over 120 minutes on d1 of every cycle G-csf : d8 to d13 systematically
- Primary Outcome Measures
Name Time Method Dose limiting toxicities up to 5 years Dose limiting toxicities occurring during the first two administered cycles.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
Institut du Cancer de Montpellier - Val d'Aurelle
🇫🇷Montpellier, France