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

Alternate Title

Lapatinib and Tamoxifen in Treating Patients With Locally Advanced or Metastatic Breast Cancer That Did Not Respond to Previous Tamoxifen

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Active	18 and over	NCI	WSU-C-2876 6724, NCI-6724, NCT00118157

Objectives

1. Determine the response rate (complete response and partial response) in patients with tamoxifen-resistant locally advanced or metastatic breast cancer treated with lapatinib and tamoxifen.

Entry Criteria

Disease Characteristics:

• Histologically or cytologically confirmed primary adenocarcinoma of the breast
  • Locally advanced or metastatic disease not amenable to curative surgery or radiotherapy
• Tamoxifen-resistant disease, defined as 1 of the following:
  • No response to initial therapy (primary resistance)
  • Disease relapse or progression after showing an initial response to therapy (secondary resistance)
• Disease progression, as documented by 1 of the following:
  • CT scan, MRI, or x-ray
  • Increase in the number of bone lesions
  • Increased pain in an area of known bony metastasis AND ≥ 2 serial tumor marker elevations
• Measurable disease, defined as ≥ 1 unidimensionally measurable target lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by MRI or spiral CT scan
  • Not in a previously irradiated area
• No rapidly progressive disease in major organs (i.e., lymphangitic spread or bulky liver metastasis)
• No known brain or leptomeningeal metastases requiring active therapy
  • Previously treated asymptomatic stable CNS metastases allowed provided patient does not require corticosteroids for CNS metastases
• Hormone receptor status:
  • Estrogen and/or progesterone receptor positive disease

Prior/Concurrent Therapy:

Biologic therapy

• Prior trastuzumab (Herceptin®) in combination with chemotherapy in the adjuvant setting only is allowed
• No prior trastuzumab in combination with hormonal therapy
• No concurrent trastuzumab

Chemotherapy

• See Biologic therapy
• Prior cumulative doxorubicin dose ≤ 450 mg/m²

Endocrine therapy

• See Disease Characteristics
• See Biologic therapy
• At least 14 days since prior and no concurrent dexamethasone or dexamethasone equivalent dose > 1.5 mg/day

Radiotherapy

• See Disease Characteristics
• More than 2 weeks since prior radiotherapy

Surgery

• More than 4 weeks since prior surgery
• More than 6 months since prior coronary or peripheral artery bypass grafting
• No prior surgical procedure affecting absorption

Other

• No prior epidermal growth factor receptor- or HER2/neu-targeting therapies
• At least 7 days since prior and no concurrent CYP3A4 inhibitors, including any of the following:
  • Clarithromycin
  • Erythromycin
  • Troleandomycin
  • Itraconazole
  • Ketoconazole
  • Voriconazole
  • Fluconazole (doses ≤ 150 mg/day allowed)
  • Fluvoxamine
  • Nefazodone
  • Verapamil
  • Diltiazem
  • Cimetidine
  • Aprepitant
  • Proton pump inhibitors
  • H2 blockers
  • Grapefruit or grapefruit juice
  • Bitter orange
• At least 14 days since prior and no concurrent CYP3A4 inducers, including any of the following:
  • Phenytoin
  • Carbamazepine
  • Phenobarbital
  • Oxcarbazepine
  • Efavirenz
  • Nevirapine
  • Rifampin
  • Rifabutin
  • Rifapentine
  • Hypericum perforatum (St. John's wort)
  • Modafinil
• At least 6 months since prior and no concurrent amiodarone
• No concurrent gastric pH modifiers within 1 hour before and after lapatinib administration
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No other concurrent antineoplastic agents
• No other concurrent investigational agents
• Concurrent zoledronate for bone metastases or hypercalcemia allowed
• Concurrent oral anticoagulants (e.g., warfarin) allowed provided there is increased vigilance in INR monitoring

Patient Characteristics:

Age

• 18 and over

Sex

• Male or female

Menopausal status

• Not specified

Performance status

• ECOG 0-2

  OR

• Karnofsky 60-100%

Life expectancy

• At least 3 months

Hematopoietic

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

Hepatic

• ALT and AST ≤ 1.5 times upper limit normal (ULN) (3 times ULN if liver metastases are present)
• Bilirubin ≤ 1.5 times ULN

Renal

• Creatinine normal

  OR

• Creatinine clearance > 60 mL/min

Cardiovascular

• Ejection fraction normal by echocardiogram or MUGA
• None of the following cardiovascular conditions within the past 6 months:
  • Myocardial infarction
  • Severe or unstable angina
  • Symptomatic congestive heart failure
  • Cerebrovascular accident or transient ischemic attack
• Deep venous thrombosis or other clinically significant thromboembolic event within the past 6 months allowed provided patient is clinically stable on anticoagulation therapy

Pulmonary

• Pulmonary embolus within the past 6 months allowed provided patient is clinically stable on anticoagulation therapy

Gastrointestinal

• No malabsorption syndrome
• No gastrointestinal (GI) tract disease that would preclude ability to take oral medication
• No requirement for IV alimentation
• No uncontrolled inflammatory GI disease (e.g., Crohn's disease or ulcerative colitis)
• Able to swallow and retain oral medication

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective barrier contraception during and for ≥ 2 weeks after completion of study treatment
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
• No history of allergic reaction attributed to compounds of similar chemical or biological composition to lapatinib
• No other severe acute or chronic medical or psychiatric condition or laboratory abnormality that would preclude study participation

Expected Enrollment

A total of 21-41 patients will be accrued for this study within 13-21 months.

Outcomes

Tumor response (complete and partial) as measured by RECIST criteria

Changes in phosphorylation in tumor tissue of epidermal growth factor receptor (EGFR), HER2, AKT kinase, MAPK, ER-Ser118, and ER-SER167

Outline

This is a multicenter study.

Patients receive oral lapatinib and oral tamoxifen once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed at 1 month and then every 3 months thereafter.

Trial Contact Information

Trial Lead Organizations

Barbara Ann Karmanos Cancer Institute

Elaina Gartner, MD, Protocol chair		Ph: 313-576-8724; 800-527-6266

U.S.A.
Michigan
	Detroit
	Barbara Ann Karmanos Cancer Institute
		Clinical Trials Office - Barbara Ann Karmanos Cancer Institute	Ph:  313-576-9363
	Sinai-Grace Hospital
		Elaina Gartner	Ph:  313-576-8724

Registry Information
Official Title		A Phase II Study of GW572016 and Tamoxifen in Patients with Metastatic Breast Cancer Resistant to Single-Agent Tamoxifen
Trial Start Date		2005-05-05
Trial Completion Date		2009-12-31 (estimated)
Registered in ClinicalTrials.gov		NCT00118157
Date Submitted to PDQ		2005-05-11
Information Last Verified		2009-10-22
NCI Grant/Contract Number		CA62487, CA30199

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