Phase I/II Study of Lapatinib in Combination With Oxaliplatin and Capecitabine in Subjects With Advanced Colorectal Cancer
- Conditions
- Neoplasms, Colorectal
- Interventions
- Registration Number
- NCT00536809
- Lead Sponsor
- GlaxoSmithKline
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 12
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Phase II lapatinib Treatinng subjects at the maximum tolerated dose of lapatinib, capecitabine, and oxaliplatin Phase II capecitabine Treatinng subjects at the maximum tolerated dose of lapatinib, capecitabine, and oxaliplatin Phase II oxaliplatin Treatinng subjects at the maximum tolerated dose of lapatinib, capecitabine, and oxaliplatin Phase I oxaliplatin Dose escalation of lapatinib along with capecitabine and oxaliplatin until the maximum tolerated dose is reached.
- Primary Outcome Measures
Name Time Method Overall Response in Phase II 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 Outcome Measures
Name Time Method 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. Exploring if there is an association with a reduction in thymidylate synthase (TS) gene expression in both plasma and tumor prior to treatment and increased sensitivity in clinical activity. This analysis was not completed due to the study being closed early and the small number of participants enrolled in Phase II.
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. DNA sequencing was done to identify genetic aberrations in somatic (tumor) DNA that may associate with clinical outcomes in response to therapy. This analysis was not completed due to the study being closed early and the small number of participants enrolled in Phase II.
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 This outcome measure was conducted to investigate a possible genetic relationship to handling or response to lapatinib, oxaliplatin, and capecitabine. This measure was not analyzed due to the small number of participants who signed the optional pharmacogenetics consent.
Change From Baseline to Study Completion in Heart Rate Baseline to study completion (up to 135 days) Each on-study and follow-up laboratory parameter and vital sign was compared to the participant's baseline values to investigate what changes occurred. This analysis was not completed due to the study being closed early and the small number of participants enrolled in Phase II.
Change From Baseline to Study Completion in Blood Pressure Baseline to study completion (up to 135 days) Each on-study and follow-up laboratory parameter and vital sign was compared to the participant's baseline values to investigate what changes occurred. This analysis was not completed due to the study being closed early and the small number of participants enrolled in Phase II.
Change From Baseline to Study Completion in Sodium, Potassium, and Calcium Baseline to study completion (up to 135 days) Each on-study and follow-up laboratory parameter and vital sign was compared to the participant's baseline values to investigate what changes occurred. This analysis was not completed due to the study being closed early and the small number of participants enrolled in Phase II.
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). A possible association between a reduction in thymidylate synthase (TS) gene expression and increased sensitivity in clinical activity was to be explored. This analysis was not completed due to the study being closed early and the small number of participants enrolled in Phase II.
Change From Baseline to Study Completion in Weight Baseline to study completion (up to 135 days) Each on-study and follow-up laboratory parameter and vital sign was compared to the participant's baseline values to investigate what changes occurred. This analysis was not completed due to the study being closed early and the small number of participants enrolled in Phase II.
Change From Baseline to Study Completion in Prothrombin Time and Partial Thromboplastin Time Baseline to study completion (up to 135 days) Each on-study and follow-up laboratory parameter and vital sign was compared to the participant's baseline values to investigate what changes occurred. This analysis was not completed due to the study being closed early and the small number of participants enrolled in Phase II.
Change From Baseline to Study Completion in International Normalized Ratio Baseline to study completion (up to 135 days) Each on-study and follow-up laboratory parameter and vital sign was compared to the participant's baseline values to investigate what changes occurred. This analysis was not completed due to the study being closed early and the small number of participants enrolled in Phase II.
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. Exploring tumor-derived biomarkers including TS, DPD, TP, EGFR (ErbB1), and additional downstream markers involved in the mechanism of action of each compound (e.g., ERCC1) and comparison to clinical response. This analysis was not completed due to the study being closed early and the small number of participants enrolled in Phase II.
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) Both participants that entered Phase II of the study were censored for progression-free survival. Progression-free survival (PFS) is defined as the time from first dose until the first documented sign of disease progression or death due to any cause. For participants who do not progress or die, PFS was censored at the time of last radiological scan preceding the initiation of alternative anti-cancer therapy. Of the 2 participants in Phase II of the study, one discontinued due to adverse events, and the other was referred for a surgical resection.
Change From Baseline to Study Completion in White Blood Cells and Platelets Baseline to study completion (up to 135 days) Each on-study and follow-up laboratory parameter and vital sign was compared to the participant's baseline values to investigate what changes occurred. This analysis was not completed due to the study being closed early and the small number of participants enrolled in Phase II.
Change From Baseline to Study Completion in Hemoglobin and Neutrophils Baseline to study completion (up to 135 days) Each on-study and follow-up laboratory parameter and vital sign was compared to the participant's baseline values to investigate what changes occurred. This analysis was not completed due to the study being closed early and the small number of participants enrolled in Phase II.
Change From Baseline to Study Completion in Creatinine, Total Bilirubin, and Direct Bilirubin Baseline to study completion (up to 135 days) Each on-study and follow-up laboratory parameter and vital sign was compared to the participant's baseline values to investigate what changes occurred. This analysis was not completed due to the study being closed early and the small number of participants enrolled in Phase II.
Change From Baseline to Study Completion in Creatinine Clearance Baseline to study completion (up to 135 days) Each on-study and follow-up laboratory parameter and vital sign was compared to the participant's baseline values to investigate what changes occurred. This analysis was not completed due to the study being closed early and the small number of participants enrolled in Phase II.
Change From Baseline to Study Completion in Aspartate Aminotransferase, Alanine Aminotranferease, and Alkaline Phosphatase Baseline to study completion (up to 135 days) Each on-study and follow-up laboratory parameter and vital sign was compared to the participant's baseline values to investigate what changes occurred. This analysis was not completed due to the study being closed early and the small number of participants enrolled in Phase II.
Trial Locations
- Locations (1)
GSK Investigational Site
🇺🇸Madison, Wisconsin, United States