Phase I/II Study of SOL for Untreated Metastatic Colorectal Cancer

NCT00524706 | Unknown Phase 1 DMC

• 1 other identifier: SCC-07-01
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

Introduction: S-1 is promising drug which could replace 5-fluorouracil plus l-leucovorin (5-FU/l-LV) in treatment of advanced colorectal cancer. Phase I/II study of S-1 plus Oxaliplatin (SOX) demonstrated its promising activity with acceptable toxicity as first-line chemotherapy in patients with untreated metastatic colorectal cancer and S-1 showed equivalent possibility to 5-FU/l-LV. On the other hand, phase I/II study of S-1 plus oral Leucovorin (S-1/LV) demonstrated that this regimen had enhanced efficacy in comparison with S-1 alone. From these results, it was expected that S-1/LV plus Oxaliplatin (SOL) would be more effective than SOX. Therefore, phase I/II study of SOL combination therapy was planned. Purpose A dose-finding study of S-1/LV plus Oxaliplatin (SOL) was planned to determine the recommended dose (RD), and to assess the response rate (RR) in patients with untreated metastatic colorectal cancer. The primary endpoints of the phase I portion are determination of the RD of SOL, and safety. The phase II portion of this study was aimed to assess the RR of SOL.

Conditions

Colorectal Cancer

Keywords

S-1; oral fluoropyrimidine; tegafur; Gimeracil; Oteracil Potassium; Leucovorin; Calcium Folinate; Oxaliplatin; L-OHP; colorectal cancer

Outcome Measures

Primary Outcomes (2)

• Determine the RD of S-1, Leucovorin, and Oxaliplatin in phase I setting

  During 2 cycles

• Evaluate the response rate of S-1, Leucovorin, and Oxaliplatin with recommended dose in phase II

  During chemotherapy

Secondary Outcomes (2)

• Phase I - Safety - Pharmacokinetic drug-drug interaction - Response rate - Time to treatment failure (TTF) - Progression free survival (PFS) - Overall survival (OS)

• Phase II - Safety - Time to treatment failure (TTF) - Progression free survival (PFS) - Overall survival (OS)

Interventions

S-1, oral Leucovorin, Oxaliplatin DRUG

Eligibility Criteria

• Age: 20 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent.
• Adequate oral intake.
• Histologically proved adenocarcinoma (colorectal cancer).
• Unresectable, recurrent and advanced colorectal cancer.
• At least 4 weeks since prior major surgery
• Age: 20 - 74 at enrollment.
• Performance Status (Eastern Cooperative Oncology Group \[ECOG\] scale): 0 - 2.
• No prior treatment (ex. radiation therapy, chemotherapy, hormonal therapy) to advanced disease. Patients who received adjuvant chemotherapy more than 180 days before enrollment can be allowed but those who received S-1 or Oxaliplatin containing treatment shall be excluded.
• Proved presence of measurable lesions within 30 days before enrollment.
• Patients with the following function of bone marrow, liver and kidney based on the laboratory values measured within 15 days before enrollment.
• Hemoglobin \>\_ 9.0g/dL
• WBC: LLN - 12,000/mm3
• Absolute granulocyte count \>\_ 1,500/mm3
• Platelets \>\_ 100,000/mm3
• Total Bilirubin \<\_ 1.5mg/dL

You may not qualify if:

• Patients who not received S-1 and Oxaliplatin as neoadjuvant or adjuvant chemotherapies before enrollment.
• Contraindication to S-1, and serious hypersensitivity to oral Leucovorin.
• No other concurrent investigational therapy.
• Patients did who not received blood transfusion and hematogenesis stimulating agents (ex. Granulocyte-Colony Stimulating Factor).
• Serious drug hypersensitivity.
• Prior history of peripheral neuropathy.
• Marked infection or inflammation (ex. patients with a fever of 38.0 degrees or higher).
• Poorly-controlled diabetes, hypertension or hypercalcemia.
• Severe (inpatient care is needed) arrhythmia, heart disease or its history.
• Severe (inpatient care is needed) lung disease (ex. interstitial pneumonia or pulmonary fibrosis).
• Psychiatric disorder requiring to receive treatment with antipsychotic drug.
• Fresh bleeding from the gastrointestinal tract.
• Requiring to drainage massive ascites, pleural effusion retention or pericardial fluid.
• Extensive bone metastasis.
• Clinically suspicious brain metastasis or brain metastasis.

Sponsors & Collaborators

• Shizuoka Cancer Center: lead

Study Sites (1)

Shizuoka Cancer Center

Shizuoka, 411-8777, Japan

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

S 1 (combination); Leucovorin; Oxaliplatin

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Coordination Complexes; Organic Chemicals

Study Officials

• Narikazu Boku, MD

  Shizuoka Cancer Cener, Division of Gastrointestinal Oncology

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: September 4, 2007
• First Posted: September 5, 2007
• Study Start: August 1, 2007
• Study Completion: April 1, 2011
• Last Updated: November 13, 2008

Record last verified: 2008-11

Locations

JP (1)