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

NCT00536809 | Completed Phase 1 Results

• 1 other identifier: EGF108991
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

Neoplasms, Colorectal

Keywords

Metastatic Colorectal Cancer; oxaliplatin; fluoropyrimidines cancers; Advanced Colorectal Cancer; capecitabine; lapatinib

Outcome Measures

Primary Outcomes (1)

• Overall Response in Phase II

  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.

  Baseline to response (up to 135 days)

Secondary Outcomes (17)

• 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.

• 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).

• 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.

• 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

Study Arms (2)

Phase I

EXPERIMENTAL

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

Drug: oxaliplatin

Phase II

EXPERIMENTAL

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

Drug: lapatinib; Drug: oxaliplatin; Drug: capecitabine

Interventions

lapatinib DRUG

onced daily Days 1-21

Phase II

oxaliplatin DRUG

Day one of each cycle

Phase I; Phase II

capecitabine DRUG

given BID days 1-14

Also known as: lapatinib, oxaliplatin

Phase II

Eligibility Criteria

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

You may qualify if:

• years of age or older.
• A female is eligible to enter and participate in the study if she is of:
• Non-child-bearing potential (i.e., physiologically incapable of becoming pregnant), including any female who:
• Has had a hysterectomy, or
• Has had a bilateral oophorectomy (ovariectomy), or
• Has had a bilateral tubal ligation, or
• Is considered post-menopausal (defined as amenorrheic for greater than or equal to 1 year).
• Childbearing potential, has a negative serum pregnancy test at Screening and agrees to one of the following from 2 weeks prior to enrolment and continue through the post-study visit:
• Complete abstinence from sexual intercourse
• Oral Contraceptive, either combined or progestogen alone (must use a back up method, if have taken for less than 3 cycles)
• Injectable progestogen
• Implants of levonorgestrel
• Estrogenic vaginal ring
• Percutaneous contraceptive patches
• Intrauterine device (IUD) or intrauterine system (IUS) with a documented failure rate of less than 1% per year

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Madison, Wisconsin, 53792, United States

Location

Related Publications (1)

• Dennie TW, Fleming RA, Bowen CJ, Dar MM, Alberti D, Oliver K, Loconte N, Mulkerin D, Holen KD. A phase I study of capecitabine, oxaliplatin, and lapatinib in metastatic or advanced solid tumors. Clin Colorectal Cancer. 2011 Mar 1;10(1):57-62. doi: 10.3816/CCC.2011.n.008.

  PMID: 21609937 DERIVED

Related Links

• Results for study EGF108991 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Lapatinib; Oxaliplatin; Capecitabine

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)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coordination Complexes; Organic Chemicals; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Limitations and Caveats

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.

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: September 27, 2007
• First Posted: September 28, 2007
• Study Start: September 26, 2007
• Primary Completion: October 31, 2008
• Study Completion: October 31, 2008
• Last Updated: December 18, 2017
• Results First Posted: June 9, 2010

Record last verified: 2017-11

Locations

US (1)