Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Related Information
Registry Information

Alternate Title

Capecitabine With or Without Lapatinib in Treating Women With Locally Advanced or Metastatic Breast Cancer That Has Not Responded to Previous Therapy

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Treatment	Closed	18 and over	Pharmaceutical / Industry	GSK-EGF100151 UCLA-0403074-01, NCT00078572

Objectives

Primary

1. Compare time to disease progression in women with refractory locally advanced or metastatic breast cancer treated with capecitabine with vs without lapatinib.

Secondary

1. Compare overall response, clinical benefit, time to response, duration of response, 6-month progression-free survival, and overall survival in patients treated with these regimens.
2. Compare the toxicity of these regimens in these patients.
3. Compare quality of life of patients treated with these regimens.
4. Compare serum concentration of ErbB2 with tumor response in patients treated with these regimens.

Entry Criteria

Disease Characteristics:

• Histologically confirmed breast cancer
  • Invasive disease
  • Stage IIIB, IIIC (with T4 lesions), or IV
  • Progressive advanced or metastatic disease, defined by 1 of the following:
    • Any new lesion not previously identified
    • Increase of ≥ 25% in existing lesions



• Refractory disease, defined as progression in the metastatic setting OR relapse within 6 months after completion of adjuvant therapy comprising (sequentially or concurrently) 4 courses of both a taxane and an anthracycline
  • Patients who progressed while receiving 2 courses of adjuvant therapy are eligible
  • Patients whose relapse is > 6 months after completion of adjuvant therapy AND further anthracycline therapy is not indicated are eligible



• Measurable disease, as defined by RECIST
  • Measurable lesions in the field of prior adjuvant radiotherapy allowed provided ≥ 8 weeks since the last radiation treatment



• Archived tumor tissue available



• ErbB2 (HER-2) overexpression (+3 by immunohistochemistry [IHC] alone OR +2 by IHC with fluorescence in situ hybridization confirmation)



• Patients must have received trastuzumab (Herceptin®) alone or in combination with chemotherapy for at least 6 weeks at standard doses



• No known history or clinical evidence of CNS metastases



• No leptomeningeal carcinomatosis



• Hormone receptor status:
  • Patients with hormone receptor-positive tumors must have had disease progression after hormonal therapy unless intolerant to hormonal therapy or hormonal therapy is not considered to be clinically appropriate

Prior/Concurrent Therapy:

Biologic therapy

• See Disease Characteristics
• More than 2 weeks since prior and no concurrent anticancer biologic therapy
• No concurrent immunotherapy

Chemotherapy

• See Disease Characteristics
• Recovered from prior chemotherapy
• No prior capecitabine
• No other concurrent anticancer chemotherapy

Endocrine therapy

• See Disease Characteristics
• More than 2 weeks since prior and no concurrent hormonal therapy
• More than 2 weeks since prior and no concurrent glucocorticoids
• More than 2 weeks since prior and no concurrent oral or IV steroids
  • Inhaled steroids allowed

Radiotherapy

• See Disease Characteristics
• Recovered from prior radiotherapy
• No concurrent anticancer radiotherapy

Surgery

• No prior resection of the stomach or small bowel
• No concurrent tumor embolization
• No concurrent surgery for advanced or metastatic cancer

Other

• More than 2 weeks since prior and no concurrent anticancer cytotoxic therapy
• More than 2 weeks since prior and no concurrent CYP3A4 inducers or inhibitors, including any of the following:
  • Clarithromycin
  • Erythromycin
  • Troleandomycin
  • Ciprofloxacin
  • Rifampin
  • Norfloxacin
  • Rifabutin
  • Delaviridine
  • Indinavir
  • Nelfinavir
  • Ritonavir
  • Saquinavir
  • Efavirenz
  • Nevirapine
  • Amprenavir
  • Lopinavir
  • Sorivudine
  • Brivudine
  • Phenytoin
  • Carbamazepine
  • Phenobarbital
  • Fluoxetine
  • Nefazodone
  • Fluvoxamine
  • Intraconazole
  • Ketoconazole
  • Fluconazole
  • Voriconazole
  • Cimetidine
• More than 2 weeks since prior and no concurrent administration of any of the following:
  • Amiodirone
  • Diltiazem
  • Pioglitazone
  • Hypericum perforatum (St. John's wort)
  • Grapefruit or grapefruit juice
  • Rifabutin
  • Mibefradil
  • Diethyldithiocarbamate
  • Gestodene
  • Mifepristone
  • Modafinil
  • Allopurinol
  • Dipyridamole
  • Folinic acid
  • Trimethoprim
• More than 30 days or 5 half-lives (whichever is longer) since prior and no concurrent systemic investigational drugs (7 days for topical investigational drugs)
• No limit to other prior therapies
• Concurrent antacids allowed provided they are not administered for 1 hour before, during, and 1 hour after administration of study drug
• No concurrent coumadin-derivative anticoagulants (e.g., warfarin, leucovorin, or phenprocouman)
• Concurrent bisphosphonates allowed provided they are started before study entry
  • No concurrent prophylactic bisphosphonates
• No other concurrent investigational agents or participation in another investigational trial

Patient Characteristics:

Age

• 18 and over

Sex

• Female

Menopausal status

• Not specified

Performance status

• ECOG 0-1

Life expectancy

• At least 12 weeks

Hematopoietic

• Absolute neutrophil count > 1,500/mm³
• Hemoglobin > 9.0 g/dL
• Platelet count > 100,000/mm³

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal (ULN) (2.5 times ULN for Gilbert's syndrome)
• AST and ALT ≤ 3 times ULN (5 times ULN if liver metastases are present)
• Albumin ≥ 2.5 g/dL

Renal

• Creatinine clearance ≥ 50 mL/min

Cardiovascular

• Ejection fraction normal by echocardiogram or MUGA
• No prior uncontrolled or symptomatic angina
• No prior uncontrolled or symptomatic arrhythmia
• No prior uncontrolled or symptomatic congestive heart failure

Gastrointestinal

• Able to swallow and retain oral medication
• No ulcerative colitis
• No disease siginificantly affecting gastrointestinal function
• No malabsorption syndrome

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 4 weeks after study participation
• No known dihydropyrimidine dehydrogenase deficiency
• No active or uncontrolled infection
• No unresolved or unstable serious toxicity from prior administration of another investigational drug
• No dementia or altered mental status
• No psychiatric condition that would preclude giving informed consent
• No disease or condition that would preclude study participation
• No serious medical disorder that would preclude patient safety
• No known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to GW572016, capecitabine, fluorouracil, or any of their excipients
• No other malignancy within the past 5 years except completely resected nonmelanoma skin cancer or successfully treated carcinoma in situ

Expected Enrollment

A total of 528 patients (264 per treatment arm) will be accrued for this study.

Outcomes

Time to progression per RECIST every 6 weeks for 24 weeks and then every 12 weeks thereafter

Overall survival measured by date of death
Response rate per RECIST every 6 weeks for 24 weeks and then every 12 weeks thereafter
Safety measured by adverse events every 6 weeks for 24 weeks and then every 12 weeks thereafter

Outline

This is a randomized, open-label, multicenter study. Patients are stratified according to disease stage (IIIB vs IV) and site of disease (visceral vs nonvisceral). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral capecitabine twice daily on days 1-14 and oral lapatinib once daily (not at the same time of day as capecitabine administration) on days 1-21.



• Arm II: Patients receive capecitabine alone as in arm I.

In both arms, courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients are followed every 12 weeks.

Geyer CE, Forster J, Lindquist D, et al.: Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med 355 (26): 2733-43, 2006.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

GlaxoSmithKline

Acurian Pre-Screening Evaluation Contact		Ph: 800-563-6537

Related Information

Website for additional information.

Registry Information
Official Title		A Phase III, Randomized, Open-Label, Multicenter Study Comparing GW572016 and Capecitabine (Xeloda) Versus Capecitabine in Women with Refractory Advanced or Metastatic Breast Cancer
Trial Start Date		2004-03-01
Registered in ClinicalTrials.gov		NCT00078572
Date Submitted to PDQ		2004-05-11
Information Last Verified		2006-04-18