Neoplasms

Digestive System Diseases

All Conditions

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Oxaliplatin

Capecitabine

Lapatinib

Antimetabolites

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Dose escalation of lapatinib along with capecitabine and oxaliplatin until the maximum tolerated dose is reached.

Treatinng subjects at the maximum tolerated dose of lapatinib, capecitabine, and oxaliplatin

lapatinib

oxaliplatin

capecitabine

GSK Clinical Trials

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.

Phase I/II Study of Lapatinib in Combination With Oxaliplatin and Capecitabine in Subjects With Advanced Colorectal Cancer

A Phase I/II Study of Lapatinib in Combination With Oxaliplatin and Capecitabine in Subjects With Advanced or Metastatic Colorectal Cancer

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.

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.

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.

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.

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.

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.

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.

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.

GlaxoSmithKline

GSK typically summarizes all AEs and all SAEs. The SAE summary will include participants with only an SAE. The data summarized below under the heading Other AEs (non-serious) are actually a summary of all AEs, which does include some SAEs.

Lapatinib (Lap.) 1000 milligrams (mg)/day administered orally on Days 1-21, oxaliplatin 130 mg/square meters (m\^2) administered intravenously on Day 1, and capecitabine 1500 mg/m\^2 administered orally twice a day on Days 1-14 of a 21-day cycle

Lap. 1000 mg/Oxaliplatin 130 mg/m^2/Capecitabine 1500 mg/m^2

Lapatinib (Lap.) 1000 milligrams (mg)/day administered orally on Days 1-21, oxaliplatin 130 mg/square meters (m\^2) administered intravenously on Day 1, and capecitabine 1500 mg/m\^2/day on Days 1-14 of a 21-day cycle

Baseline participants include the 10 participants who completed Phase I, and the 2 who were enrolled into Phase II before the study was terminated.

Age, Continuous

Sex: Female, Male

White/Caucasian/European heritage

Race/Ethnicity, Customized

Phase II of the study was terminated due to lake of interest. Two participants were enrolled prior to termination. Due to the small sample size in Phase II, the data were not analyzed. The two participants' data were analyzed with Phase I data.

GSK Response Center

All-Treated Population for Phase II: all participants who received at least one dose of lapatinib

Overall Response in Phase II

Relationship Between Pretreatment Plasma TS mRNA and Pretreatment Tumor TS mRNA in Colon Tumor Biopsies.

Effect of Lapatinib, Oxaliplatin, and Capecitabine on Plasma TS mRNA and the Relationship Between Plasma TS mRNA and Clinical Response

Tumor-derived Biomarkers (Encoded in Protein or RNA) Associated With Clinical Outcome to Treatment

Genetic Aberrations in Somatic (Tumor) DNA Derived From the Tumor Tissue Biopsies That May Associate With Clinical Outcomes in Response to Therapy

Participants in the All-Treated Population who signed a PGx informed consent.

Genetic Variants in Germline (Host) DNA and Comparison to the Efficacy and Safety of the Study Drugs

Progression-free Survival (PFS) After Lapatinib, Oxaliplatin, and Capecitabine Administered at the MTD Level of Phase II

Change From Baseline to Study Completion in Weight

Change From Baseline to Study Completion in Heart Rate

Change From Baseline to Study Completion in Blood Pressure

Change From Baseline to Study Completion in Hemoglobin and Neutrophils

Change From Baseline to Study Completion in White Blood Cells and Platelets

Change From Baseline to Study Completion in Prothrombin Time and Partial Thromboplastin Time

Change From Baseline to Study Completion in International Normalized Ratio

Change From Baseline to Study Completion in Sodium, Potassium, and Calcium

Change From Baseline to Study Completion in Creatinine, Total Bilirubin, and Direct Bilirubin

Change From Baseline to Study Completion in Creatinine Clearance

Change From Baseline to Study Completion in Aspartate Aminotransferase, Alanine Aminotranferease, and Alkaline Phosphatase

Phase I: Dose escalation to a maximum tolerated dose of lapatinib 1000 milligrams (mg)/day administered orally on Days 1-21, oxaliplatin 130 mg/square meters (m\^2) administered intravenously on Day 1, and capecitabine 1500 mg/m\^2/day on Days 1-14 of a 21-day cycle. Phase II: Lapatinib 1000 mg/day administered orally on Days 1-21, oxaliplatin 130 mg/m\^2 administered intravenously on Day 1, and capecitabine 1500 mg/m\^2/day on Days 1-14 of a 21-day cycle.

Spots Global Cancer Trial Database for Phase I/II Study of Lapatinib in Combination With Oxaliplatin and Capecitabine in Subjects With Advanced Colorectal Cancer

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