Lapatinib in Combination With Capecitabine in Japanese Patients With Metastatic Breast Cancer

NCT00477464 | Completed Phase 2 Results DMC

• 1 other identifier: 109749
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 15

Brief Summary

This study is to evaluate the safety and efficacy of lapatinib taken together with capecitabine in Japanese patients. The study will proceed in two phases; the first phase(Part1) will lead to an evaluation of the mainly tolerability as well as PK parameters. If there are no major safety concerns in Part 1, the study will move into the second phase (Part 2) to further evaluate the safety and clinical activity.

Conditions

Metastatic Breast Cancer; Neoplasms, Breast

Keywords

dual kinase inhibitor,; EGFR/ErbB1,; ErbB2-overexpressing,; GW572016,; advanced/metastatic breast cancer, Lapatinib,; HER-2/new,; pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• Clinical Benefit Response (Independent Reviewer-assessed)

  CBR is defined as the percentage of participants receiving at least one dose of study medication who achieved a best overall response classified as a complete or partial (confirmed) tumor response or stable disease for at least 6 months (24 weeks). A "complete response" is defined as the disappearance of all target or non-target lesions, "partial response" and "disease progression" as at least a 30% decrease and at least a 20% increase, respectively, in the sum of the longest diameter of target lesions, and "stable disease" as neither "partial response" nor "disease progression."

  Baseline, every 6 weeks until Week 24 and then every 12 weeks until disease progression (up to Week 119)

Secondary Outcomes (19)

• Time to Progression (Independent Reviewer-assessed)

  Baseline, every 6 weeks until Week 24 and then every 12 weeks until disease progression or death due to breast cancer (up to Week 119)

• Progression-free Survival (PFS) (Independent Reviewer-assessed)

  Baseline, every 6 weeks until Week 24 and then every 12 weeks until disease progression or death (up to Week 119)

• 6-Month Progression-free Survival (Independent Reviewer-assessed)

  Baseline and then every 6 weeks until Month 6 (Week 24)

• Objective Response (Independent Reviewer-assessed)

  Baseline every 6 weeks until Week 24 and then every 12 weeks until disease progression or death (up to Week 119)

• Overall Survival (Independent Reviewer-assessed)

  Baseline and then followed every 4 weeks until death (up to Week 157.9) while on treatment. After treatment termination, followed every 12 weeks until death (up to Week 157.9)

Study Arms (1)

Lapatinib+capecitabine

EXPERIMENTAL

Lapatinib 1250mg once daily +capecitabine 2000mg/m\^2 twice daily (14 days out of 21 days)

Drug: Lapatinib; Drug: capecitabine

Interventions

Lapatinib DRUG

1250mg once daily

Lapatinib+capecitabine

capecitabine DRUG

2000mg/m\^2 twice daily (14 days out of 21 days)

Lapatinib+capecitabine

Eligibility Criteria

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

You may qualify if:

• Subjects eligible for enrolment in the study must meet all of the following criteria:
• Patients who have consent to this study participation and signed into Informed consent form.
• Subjects must have histologically confirmed invasive breast cancer with stage IIIB, stage IIIC with T4 lesion, or stage IV disease.
• Documentation of ErbB2 overexpression \[IHC3+ or IHC2+ with FISH confirmation\] is required based on local laboratory.
• Subjects must have documented progressive advanced or metastatic breast cancer.
• Subjects must have refractory breast cancer defined as progression in the locally advanced or metastatic setting or relapse within 6 months of completing adjuvant therapy. Prior therapies must include, but are not limited to:
• Taxane containing regimen for at least 4 cycles or 2 cycles provided disease progression occurred while on taxane.
• Anthracycline containing regimen for at least 4 cycles or 2 cycles provided disease progression occurred while on anthracycline.
• Subjects who relapse \>6 months after completion of adjuvant anthracycline-containing chemotherapy, and for whom further anthracycline is not indicated, will be considered to have met the anthracycline prior exposure requirement.
• Taxanes and anthracyclines may have been administered concurrently or separately.
• Prior treatment with capecitabine is not permitted.
• Prior treatment must have contained trastuzumab alone or in combination with other chemotherapy for at least 6 weeks of standard doses in the adjuvant or advanced/metastatic setting.
• Subjects with hormone receptor positive tumors must have disease progression following hormonal therapy unless intolerant to hormonal therapy or hormonal therapy is not considered to be clinically appropriate.
• Subjects with stable CNS metastases (asymptomatic, and off systemic steroids and anticonvulsants for at least 3 months) are eligible.
• Measurable disease according to modified RECIST (Response Evaluation Criteria in Solid Tumors) (see Section 6.2, Efficacy p.49).

You may not qualify if:

• Subjects meeting any of the following criteria must not be enrolled in the study:
• Pregnant or lactating females.
• Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel. In addition, subjects with ulcerative colitis are excluded.
• History of other malignancy. Subjects who have been disease-free for at least 5 years or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible.
• Unresolved or unstable, serious toxicity from prior administration of another investigational drug and/or of prior anticancer therapy.
• Active or uncontrolled infection.
• Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent.
• Known history of uncontrolled or symptomatic angina, arrhythmia or congestive heart failure.
• No prior anti-ErbB1/ErbB2 inhibitor for breast cancer other than trastuzumab.
• Known history or clinical evidence of leptomeningeal carcinomatosis.
• Concurrent anticancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy, biologic therapy, or tumor embolization) other than capecitabine.
• Bisphosphonates for the treatment of bone metastases should not be initiated following the first dose of study medication. Prophylactic use of bisphosphonate in subjects without bone disease is not permitted, except for prevention of osteoporosis.
• Use of an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of study medication.
• Participation in other studies or use of other investigational drugs during this study.
• Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to lapatinib or excipients of lapatinib.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (15)

GSK Investigational Site

Aichi, 464-8681, Japan

Location

GSK Investigational Site

Chiba, 277-8577, Japan

Location

GSK Investigational Site

Ehime, 791-0280, Japan

Location

GSK Investigational Site

Fukuoka, 811-1395, Japan

Location

GSK Investigational Site

Hokkaido, 003-0804, Japan

Location

GSK Investigational Site

Ibaraki, 305-8576, Japan

Location

GSK Investigational Site

Kagoshima, 892-0833, Japan

Location

GSK Investigational Site

Osaka, 540-0006, Japan

Location

GSK Investigational Site

Osaka, 553-0003, Japan

Location

GSK Investigational Site

Shizuoka, 411-8777, Japan

Location

GSK Investigational Site

Tochigi, 329-0498, Japan

Location

GSK Investigational Site

Tokyo, 104-0045, Japan

Location

GSK Investigational Site

Tokyo, 104-8560, Japan

Location

GSK Investigational Site

Tokyo, 113-8677, Japan

Location

GSK Investigational Site

Tokyo, 135-8550, Japan

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Lapatinib; Capecitabine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

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

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 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 22, 2007
• First Posted: May 23, 2007
• Study Start: June 1, 2007
• Primary Completion: December 1, 2010
• Study Completion: December 1, 2010
• Last Updated: September 17, 2018
• Results First Posted: September 5, 2011

Record last verified: 2011-09

Locations

JP (15)