This trial is active, not recruiting.

Conditions breast cancer, male breast cancer, recurrent breast cancer, stage iiib breast cancer, stage iiic breast cancer, stage iv breast cancer
Treatments lapatinib ditosylate, tamoxifen citrate
Phase phase 2
Sponsor National Cancer Institute (NCI)
Start date May 2005
End date July 2011
Trial size 41 participants
Trial identifier NCT00118157, 6724, C-2876, CDR0000433388, NCI-2009-00080, U01CA062487


This phase II trial is studying how well giving lapatinib together with tamoxifen works in treating patients with locally advanced or metastatic breast cancer that did not respond to previous tamoxifen. Lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Estrogen can cause the growth of breast cancer cells. Hormone therapy using tamoxifen may fight breast cancer by blocking the use of estrogen by the tumor cells. Sometimes when tamoxifen is given, it does not stop the growth of tumor cells. The tumor is said to be resistant to tamoxifen. Giving lapatinib together with tamoxifen may reduce drug resistance and allow the tumor cells to be killed.

United States No locations recruiting
Other countries No locations recruiting

Study Design

Endpoint classification efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Patients receive oral lapatinib and oral tamoxifen once daily on days 1-28.
lapatinib ditosylate
Given orally
tamoxifen citrate
Given orally

Primary Outcomes

Tumor response rate (complete and partial) assessed by Response Evaluation Criteria in Solid Tumors (RECIST)
time frame: 4 weeks

Secondary Outcomes

Changes in phosphorylation in tumor tissue of epidermal growth factor receptor (EGFR), HER2, AKT kinase, MAPK, ER-Ser118, and ER-SER167
time frame: Baseline and at 21 days

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - 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. - 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 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 present) - 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 therapy. - 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 medication. - 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 colitis). - 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.

Additional Information

Official title A Phase II Study of GW572016 and Tamoxifen in Patients With Metastatic Breast Cancer Resistant to Single-Agent Tamoxifen
Principal investigator Elaina Gartner
Description OBJECTIVES: 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 tamoxifen. 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.
Trial information was received from ClinicalTrials.gov and was last updated in October 2013.
Information provided to ClinicalTrials.gov by National Cancer Institute (NCI).