Capecitabine (XELODA) With Or Without Lapatinib (GW572016) For Women With Refractory Advanced or Metastatic Breast Cancer

NCT00078572 | Completed Phase 3 DMC

• 1 other identifier: 100151
• Study Type: interventional
• Target: 408
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study was designed to compare the efficacy and safety of an oral dual tyrosine kinase inhibitor in combination with capecitabine versus capecitabine alone in women with locally advanced or metastatic breast cancer that has not responded to previous therapy.

Conditions

Breast Cancer

Keywords

XELODA; Metastatic; Breast Cancer; Advanced; HERCEPTIN

Outcome Measures

Primary Outcomes (1)

• Time to progression

  randomization to time of progression or death due to breast cancer

Secondary Outcomes (9)

• Overall survival

  from randomization until death due to any cause

• progression-free survival

  time from randomization until first documented sign of disease progression

• 6-month progression-free survival

  six months after the date of randomization

• overall tumor response rate (percentage of subjects achieving complete response (CR) or partial response (PR)

  response after randomization

• clinical benefit rate (percentage of subjects with CR or PR or stable disease [SD] for ≥6 months)

  response after randomization

Study Arms (2)

capecitabine alone

ACTIVE COMPARATOR

Capecitabine daily dose divided and given twice daily orally, for 14 days, every 21 days. The capecitabine starting dose for the monotherapy arm was 2500 mg/m2. Randomization is 1:1.

Drug: capecitabine

Combination

EXPERIMENTAL

Lapatinib 1250 mg once daily plus capecitbine daily dose divided and given twice daily orally, for 14 days, every 21 days. The capecitabine starting dose for the combination arm was 2000 mg/m2.

Drug: capecitabine; Drug: lapatinib (GW572016)

Interventions

capecitabine DRUG

Capecitabine daily dose divided and given twice daily orally, for 14 days, every 21 days. The capecitabine starting dose for the monotherapy arm was 2500 mg/m2 and for the combination arm was 2000 mg/m2.

Combination; capecitabine alone

lapatinib (GW572016) DRUG

Lapatinib 1250 mg orally once daily

Combination

Eligibility Criteria

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

You may qualify if:

• Signed informed consent
• Patients must have histologically confirmed invasive breast cancer with stage IIIb, stage IIIc with T4 lesion, or stage IV disease
• Documentation of ErbB2 overexpression (immunohistochemistry (IHC) 3+ or IHC 2+ with fluorescence in situ hybridization (FISH) confirmation) is required based on local laboratory or initial diagnostic results. Where testing is not feasible, central laboratory testing will be utilized
• Subjects must have documented progressive advanced or metastatic breast cancer. Progression for entry is defined as appearance of any new lesion not previously identified or increase of 25% or more in existent lesions and must be documented
• 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
• 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 central nervous system (CNS) metastases (asymptomatic and off systemic steroids and anticonvulsants for at least 3 months) are eligible
• Female subjects must be≥18 years of age
• Eastern Cooperative Oncology Group (ECOG Performance Status of 0 or 1
• Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST)

You may not qualify if:

• Pregnant or lactating females at anytime during the study
• Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel. In addition, subjects with ulcerative colitis are also excluded
• History of other malignancy. Subjects who have been disease-free for 5 years or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible
• Concurrent disease or condition that would make the subject inappropriate for study participation, or any serious medical disorder that would interfere with the subject's safety
• Unresolved or unstable serious toxicity from prior administration of another investigational drug
• 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 anti-cancer 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 randomized therapy. Prophylactic use of bisphosphonates in subjects without bone disease is not permitted, except for prevention of osteoporosis
• Concurrent treatment with an investigational agent or participation in another clinical trial
• Use of an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of study medication
• Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to GW572016 or excipients of GW572016

Sponsors & Collaborators

• GlaxoSmithKline: lead

Related Publications (4)

• Geyer CE, Forster J, Lindquist D, Chan S, Romieu CG, Pienkowski T, Jagiello-Gruszfeld A, Crown J, Chan A, Kaufman B, Skarlos D, Campone M, Davidson N, Berger M, Oliva C, Rubin SD, Stein S, Cameron D. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med. 2006 Dec 28;355(26):2733-43. doi: 10.1056/NEJMoa064320.

  PMID: 17192538 BACKGROUND

• Cameron D, Casey M, Press M, Lindquist D, Pienkowski T, Romieu CG, Chan S, Jagiello-Gruszfeld A, Kaufman B, Crown J, Chan A, Campone M, Viens P, Davidson N, Gorbounova V, Raats JI, Skarlos D, Newstat B, Roychowdhury D, Paoletti P, Oliva C, Rubin S, Stein S, Geyer CE. A phase III randomized comparison of lapatinib plus capecitabine versus capecitabine alone in women with advanced breast cancer that has progressed on trastuzumab: updated efficacy and biomarker analyses. Breast Cancer Res Treat. 2008 Dec;112(3):533-43. doi: 10.1007/s10549-007-9885-0. Epub 2008 Jan 11.

  PMID: 18188694 RESULT

• Cameron D, Casey M, Oliva C, Newstat B, Imwalle B, Geyer CE. Lapatinib plus capecitabine in women with HER-2-positive advanced breast cancer: final survival analysis of a phase III randomized trial. Oncologist. 2010;15(9):924-34. doi: 10.1634/theoncologist.2009-0181. Epub 2010 Aug 24.

  PMID: 20736298 RESULT

• Labonte MJ, Wilson PM, Yang D, Zhang W, Ladner RD, Ning Y, Gerger A, Bohanes PO, Benhaim L, El-Khoueiry R, El-Khoueiry A, Lenz HJ. The Cyclin D1 (CCND1) A870G polymorphism predicts clinical outcome to lapatinib and capecitabine in HER2-positive metastatic breast cancer. Ann Oncol. 2012 Jun;23(6):1455-64. doi: 10.1093/annonc/mdr445. Epub 2011 Oct 11.

  PMID: 21989330 DERIVED

MeSH Terms

Conditions

Breast Neoplasms; Neoplasm Metastasis

Interventions

Capecitabine; Lapatinib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: March 1, 2004
• First Posted: March 3, 2004
• Study Start: March 1, 2004
• Primary Completion: April 1, 2006
• Study Completion: February 1, 2010
• Last Updated: December 13, 2010

Record last verified: 2010-12