A Trial Assessing Several Schedules of Oral S-1 in Combination With a Fixed Dose of Oxaliplatin and Irinotecan

• Status: Completed
• Trial end date: 2018-09-01
• Target enrollment: 0
• Participant gender: All

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).

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Institut du Cancer de Montpellier - Val d'Aurelle
• Treatments: Camptothecin; Irinotecan; Oxaliplatin

Criteria

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