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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00118157
First received: July 8, 2005
Last updated: October 7, 2013
Last verified: October 2013
  Purpose

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.


Condition Intervention Phase
Breast Cancer
Male Breast Cancer
Recurrent Breast Cancer
Stage IIIB Breast Cancer
Stage IIIC Breast Cancer
Stage IV Breast Cancer
Drug: lapatinib ditosylate
Drug: tamoxifen citrate
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of GW572016 and Tamoxifen in Patients With Metastatic Breast Cancer Resistant to Single-Agent Tamoxifen

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Tumor response rate (complete and partial) assessed by Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 41
Study Start Date: May 2005
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1
Patients receive oral lapatinib and oral tamoxifen once daily on days 1-28.
Drug: lapatinib ditosylate
Given orally
Drug: tamoxifen citrate
Given orally

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00118157

Locations
United States, Michigan
Wayne State University
Detroit, Michigan, United States, 48202
Sponsors and Collaborators
Investigators
Principal Investigator: Elaina Gartner Wayne State University
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00118157     History of Changes
Other Study ID Numbers: NCI-2009-00080, NCI-2009-00080, CDR0000433388, C-2876, 6724, U01CA062487
Study First Received: July 8, 2005
Last Updated: October 7, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Breast Neoplasms
Breast Neoplasms, Male
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Lapatinib
Tamoxifen
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Estrogen Receptor Modulators
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Selective Estrogen Receptor Modulators
Bone Density Conservation Agents

ClinicalTrials.gov processed this record on September 18, 2014