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A Phase II Study of GW572016 and Tamoxifen in Patients With Metastatic Breast Cancer Resistant to Single-Agent Tamoxifen

Phase 2
18 Years
Open (Enrolling)
Breast Cancer, Male Breast Cancer, Recurrent Breast Cancer, Stage IIIB Breast Cancer, Stage IIIC Breast Cancer, Stage IV Breast Cancer

Thank you

Trial Information

A Phase II Study of GW572016 and Tamoxifen in Patients With Metastatic Breast Cancer Resistant to Single-Agent Tamoxifen


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

II. To describe the changes in phosphorylation of EGFR, her2, AKT kinase, MAPK, ER-Ser118,
and ER-Ser167 in tumor tissue after administration of tamoxifen and GW572016.

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.

Tumor tissue samples are collected at baseline and at 21 days after the beginning of study
therapy for phosphorylation of EGFR, her2, AKT kinase, MAPK, ER-Ser118, and ER-Ser167
analysis by IHC and Western blot assays.

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

Inclusion Criteria:

- At least 7 days since prior and no concurrent CYP3A4 inhibitors, including any of the

- 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

- 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

- No concurrent combination antiretroviral therapy for HIV-positive patients.

- No other concurrent antineoplastic agents.

- Histologically or cytologically confirmed primary adenocarcinoma of the breast:
Locally advanced or metastatic disease not amenable to curative surgery or

- 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 and not in a
previously irradiated area.

- No other concurrent investigational agents.

- No known brain or leptomeningeal metastases requiring active therapy.

- No rapidly progressive disease in major organs (i.e., lymphangitic spread or bulky
liver metastasis).

- Estrogen and/or progesterone receptor positive disease.

- Concurrent zoledronate for bone metastases or hypercalcemia allowed.

- Concurrent oral anticoagulants (e.g., warfarin) allowed provided there is increased
vigilance in INR monitoring.

- ECOG 0-2 or Karnofsky 60-100%

- At least 3 months life expectancy

- Absolute neutrophil count ≥ 1,500/mm3

- Platelet count ≥ 100,000/mm3

- Hemoglobin ≥ 9.0 g/dL

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

- Bilirubin ≤ 1.5 times ULN

- Creatinine normal or creatinine clearance > 60 mL/min

- 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

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

- No malabsorption syndrome

- No requirement for IV alimentation

- Able to swallow and retain oral medication

- Not pregnant or nursing

- No gastrointestinal (GI) tract disease that would preclude ability to take oral

- No other severe acute or chronic medical or psychiatric condition or laboratory
abnormality that would preclude study participation.

- No history of allergic reaction attributed to compounds of similar chemical or
biological composition to lapatinib.

- No uncontrolled inflammatory GI disease (e.g., Crohn's disease or ulcerative

- 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.

- 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.

- Prior cumulative doxorubicin dose =< 450 mg/m2.

- At least 14 days since prior and no concurrent dexamethasone or dexamethasone
equivalent dose > 1.5 mg/day.

- More than 2 weeks since prior radiotherapy.

- 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.

- No prior epidermal growth factor receptor- or HER2/neu-targeting therapies.

- Previously treated asymptomatic stable CNS metastases allowed provided patient does
not require corticosteroids for CNS metastases.

Exclusion Criteria:

- Estrogen receptor status unknown.

- History of myocardial infarction within 6 months.

- Performance status 3 or 4.

- Progesterone receptor status unknown.

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Tumor response rate (complete and partial) assessed by Response Evaluation Criteria in Solid Tumors (RECIST)

Outcome Time Frame:

4 weeks

Safety Issue:


Principal Investigator

Elaina Gartner

Investigator Role:

Principal Investigator

Investigator Affiliation:

Wayne State University


United States: Food and Drug Administration

Study ID:




Start Date:

May 2005

Completion Date:

Related Keywords:

  • Breast Cancer
  • Male Breast Cancer
  • Recurrent Breast Cancer
  • Stage IIIB Breast Cancer
  • Stage IIIC Breast Cancer
  • Stage IV Breast Cancer
  • Breast Neoplasms
  • Breast Neoplasms, Male



Wayne State University Detroit, Michigan  48202