A Phase I/II Study of Lapatinib in Combination With Oxaliplatin and Capecitabine in Subjects With Advanced or Metastatic Colorectal Cancer
Overview
- Phase
- Phase 1
- Intervention
- capecitabine
- Conditions
- Neoplasms, Colorectal
- Sponsor
- GlaxoSmithKline
- Enrollment
- 12
- Locations
- 1
- Primary Endpoint
- Overall Response in Phase II
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief Summary
The purpose of this study is to determine the highest, tolerated dose level and safety of lapatinib, capecitabine and oxaliplatin in subjects with advanced cancer and to determine the clinical activity of the combination of drugs in subjects with previously untreated advanced or metastatic colorectal cancer.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Phase II
Treatinng subjects at the maximum tolerated dose of lapatinib, capecitabine, and oxaliplatin
Intervention: capecitabine
Phase I
Dose escalation of lapatinib along with capecitabine and oxaliplatin until the maximum tolerated dose is reached.
Intervention: oxaliplatin
Phase II
Treatinng subjects at the maximum tolerated dose of lapatinib, capecitabine, and oxaliplatin
Intervention: lapatinib
Phase II
Treatinng subjects at the maximum tolerated dose of lapatinib, capecitabine, and oxaliplatin
Intervention: oxaliplatin
Outcomes
Primary Outcomes
Overall Response in Phase II
Time Frame: Baseline to response (up to 135 days)
The overall response is defined as the number of participants whose tumor response was classified as a complete response (CR; disappearance of all target lesions) or partial response (PR; 30% decrease in the sum of the longest diameter of target lesions) per Response Evaluation Criteria in Solid Tumors. Response was measured for participants in Phase II only. To determine response, radiographic images were taken at baseline, 8 weeks, and every 8 weeks thereafter until the participant withdrew from the study.
Secondary Outcomes
- Relationship Between Pretreatment Plasma TS mRNA and Pretreatment Tumor TS mRNA in Colon Tumor Biopsies.(Plasma TS mRNA is collected at screening. Pre-treatment tumor sample can be archived tissue if collected within 5 years from screening; if not, tumor sample should be collected at screening.)
- Genetic Aberrations in Somatic (Tumor) DNA Derived From the Tumor Tissue Biopsies That May Associate With Clinical Outcomes in Response to Therapy(Pre-treatment tumor sample should have been provided for the most recent biopsy (not older than 5 years) prior to dosing. The post-treatment sample is suggested, not mandatory, and should have been collected at end of Cycle 2, +/-3 days from Cycle 3.)
- Genetic Variants in Germline (Host) DNA and Comparison to the Efficacy and Safety of the Study Drugs(Optional pharmacogenetics sample may be collected at any time during the study after consent has been obtained; however, it is recommended that it be collected at the earliest time point possible)
- Change From Baseline to Study Completion in Heart Rate(Baseline to study completion (up to 135 days))
- Change From Baseline to Study Completion in Blood Pressure(Baseline to study completion (up to 135 days))
- Change From Baseline to Study Completion in Sodium, Potassium, and Calcium(Baseline to study completion (up to 135 days))
- Effect of Lapatinib, Oxaliplatin, and Capecitabine on Plasma TS mRNA and the Relationship Between Plasma TS mRNA and Clinical Response(Blood samples were collected to determine TS levels at screening phase; Days 43 and 85; after every 2 cycles of treatment (+/- 3 days); and at discontinuation (if possible).)
- Change From Baseline to Study Completion in Weight(Baseline to study completion (up to 135 days))
- Change From Baseline to Study Completion in Prothrombin Time and Partial Thromboplastin Time(Baseline to study completion (up to 135 days))
- Change From Baseline to Study Completion in International Normalized Ratio(Baseline to study completion (up to 135 days))
- Tumor-derived Biomarkers (Encoded in Protein or RNA) Associated With Clinical Outcome to Treatment(Pre-treatment tumor sample should have been provided for the most recent biopsy (not older than 5 years) prior to dosing. The post-treatment sample is suggested, not mandatory, and should have been collected at 43 +/-3 days.)
- Progression-free Survival (PFS) After Lapatinib, Oxaliplatin, and Capecitabine Administered at the MTD Level of Phase II(Date of the first dose of study drug to the date of documented and confirmed progression by clinical, radiographic, or biochemical criteria, whichever occurred earliest, or to date of death due to any causes (up to 135 Days))
- Change From Baseline to Study Completion in White Blood Cells and Platelets(Baseline to study completion (up to 135 days))
- Change From Baseline to Study Completion in Creatinine, Total Bilirubin, and Direct Bilirubin(Baseline to study completion (up to 135 days))
- Change From Baseline to Study Completion in Hemoglobin and Neutrophils(Baseline to study completion (up to 135 days))
- Change From Baseline to Study Completion in Creatinine Clearance(Baseline to study completion (up to 135 days))
- Change From Baseline to Study Completion in Aspartate Aminotransferase, Alanine Aminotranferease, and Alkaline Phosphatase(Baseline to study completion (up to 135 days))