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

NCT02387138 | Completed Phase 1

• 1 other identifier: ICM2013/47
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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).

Conditions

Digestive Cancer

Outcome Measures

Primary Outcomes (1)

• Dose limiting toxicities

  Dose limiting toxicities occurring during the first two administered cycles.

  up to 5 years

Study Arms (1)

SIRINOX

EXPERIMENTAL

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

Drug: S-1; Drug: Irinotecan; Drug: Oxaliplatin; Other: G-csf

Interventions

S-1 DRUG

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).

SIRINOX

Irinotecan DRUG

Irinotecan : fixed dose of 180 mg/m² IV over 90 minutes on d1 of every cycle

SIRINOX

Oxaliplatin DRUG

Oxaliplatin : fixed dose of 85 mg/m² over 120 minutes on d1 of every cycle

SIRINOX

G-csf OTHER

G-csf : d8 to d13 systematically

SIRINOX

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Institut du Cancer de Montpellier - Val d'Aurelle: lead

Study Sites (1)

Institut du Cancer de Montpellier - Val d'Aurelle

Montpellier, 34298, France

Location

MeSH Terms

Conditions

Gastrointestinal Neoplasms

Interventions

S 1 (combination); Irinotecan; Oxaliplatin; Granulocyte Colony-Stimulating Factor

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds; Coordination Complexes; Organic Chemicals; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• SAMALIN Emmanuelle, MD

  Institut regional du Cancer Montpellier

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 3, 2015
• First Posted: March 12, 2015
• Study Start: April 1, 2014
• Primary Completion: June 1, 2018
• Study Completion: September 1, 2018
• Last Updated: August 22, 2019

Record last verified: 2017-08

Locations

FR (1)