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

NCT00118157 | Completed Phase 2 Results

• 6 other identifiers: NCI-2009-00080CDR0000433388C-28766724P30CA022453U01CA062487
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 2

Brief Summary

This phase II trial studies how well giving lapatinib ditosylate together with tamoxifen citrate works in treating patients with breast cancer that has spread from where it started to nearby tissue or lymph nodes or to other areas of the body and did not respond to previous treatment with tamoxifen citrate. Lapatinib ditosylate 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 citrate may fight breast cancer by blocking the use of estrogen by the tumor cells. Sometimes when tamoxifen citrate is given, it does not stop the growth of tumor cells. The tumor is said to be resistant to tamoxifen citrate. Giving lapatinib ditosylate together with tamoxifen citrate may reduce drug resistance and allow the tumor cells to be killed.

Conditions

Estrogen Receptor Positive; Male Breast Carcinoma; Progesterone Receptor Positive; Recurrent Breast Carcinoma; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Tumor Response Rate (Complete and Partial) Assessed by Response Evaluation Criteria in Solid Tumors (RECIST)

  4 weeks

Secondary Outcomes (1)

• Changes in Phosphorylation in Tumor Tissue of Epidermal Growth Factor Receptor (EGFR), HER2, AKT Kinase, MAPK, ER-Ser118, and ER-SER167

  Baseline and at 21 days

Study Arms (1)

Treatment (lapatinib, tamoxifen)

EXPERIMENTAL

Patients receive lapatinib ditosylate PO daily and tamoxifen citrate PO daily. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Other: Laboratory Biomarker Analysis; Drug: Lapatinib Ditosylate; Drug: Tamoxifen Citrate

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (lapatinib, tamoxifen)

Lapatinib Ditosylate DRUG

Given PO

Also known as: Tykerb

Treatment (lapatinib, tamoxifen)

Tamoxifen Citrate DRUG

Given PO

Also known as: Apo-Tamox, Clonoxifen, Dignotamoxi, Ebefen, Emblon, Estroxyn, Fentamox, Gen-Tamoxifen, Genox, ICI 46,474, ICI-46474, Jenoxifen, Kessar, Ledertam, Lesporene, Nolgen, Noltam, Nolvadex, Nolvadex-D, Nourytam, Novo-Tamoxifen, Novofen, Noxitem, Oestrifen, Oncotam, PMS-Tamoxifen, Soltamox, TAM, Tamax, Tamaxin, Tamifen, Tamizam, Tamofen, Tamoxasta, Tamoxifeni Citras, Zemide

Treatment (lapatinib, tamoxifen)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Primary adenocarcinoma of the breast confirmed by histology or cytology
• Locally advanced or metastatic disease not amenable to surgery or radiation therapy with curative intent
• Estrogen and/or progesterone receptor positive cancer
• Patients have failed hormonal manipulation with tamoxifen, either showing no response (primary resistance) to initial therapy or relapse/progression after showing initial response (secondary failure)
• At least 1 measurable (target) lesion (i.e. any malignant tumor mass that can be accurately measured in at least 1 dimension, \>= 20 mm with conventional radiographic techniques or \>= 10 mm with magnetic resonance imaging \[MRI\] or spiral computerized tomography \[CT\] scans), in a previously un-irradiated area
• No more than 450 mg/m\^2 of prior doxorubicin
• Life expectancy \>= 3 months
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
• Absolute neutrophil count (ANC) \>= 1500/mm\^3
• Platelets \>= 100,000/mm\^3
• Hemoglobin \>= 9.0 g/dL
• Creatinine (Cr) =\< upper limit of normal (ULN) or Cr clearance \> 60 mL/min/m\^2
• Total bilirubin =\< 1.5 x ULN
• Alanine aminotransferase (ALT) =\< 1.5 x ULN or =\< 3 x ULN with liver metastases
• Aspartate aminotransferase (AST) =\< 5 x ULN or =\< 3 x ULN with liver metastases

You may not qualify if:

• Patients who have had prior treatment with EGFR and or Her-2 targeting therapies (prior trastuzumab combined with chemotherapy in the adjuvant setting only is allowed, but the combination of trastuzumab with hormonal therapy is not allowed)
• Current treatment with any other anti-neoplastic agent, including trastuzumab; patients may continue to receive zoledronic acid for bone metastases or hypercalcemia
• Radiation therapy within 2 weeks of enrollment or surgery within 4 weeks
• Rapidly progressive disease in major organs (i.e. lymphangitic spread, bulky liver metastasis) or known brain/leptomeningeal metastatic disease requiring active therapy; (patients with asymptomatic, stable previously treated metastases to the central nervous system and surrounding tissues are eligible; however patients must not have a requirement for corticosteroids due to central nervous system metastases at the time of study entry)
• Any of the following conditions within 6 months of enrollment: myocardial infarction, severe/unstable angina, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, coronary/peripheral artery bypass grafting; patients who have experienced a pulmonary embolus, deep venous thrombosis or other clinically significant thromboembolic event within 6 months of enrollment are eligible if they are clinically stable on anticoagulation therapy
• Pregnancy or breast feeding; breastfeeding should be discontinued if the mother is treated with GW572016; female patients must agree to use effective contraception during the study period, be surgically sterile, or be post-menopausal; in addition, male patients will be required to use effective contraception during the study period or be surgically sterile; the definition of effective contraception will be based on the judgment of the investigator
• Human immunodeficiency virus (HIV)-positive patients receiving combination anti-retroviral therapy are excluded from the study
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to GW572016
• Patients with gastrointestinal (GI) tract disease resulting in an inability to take oral medication, malabsorption syndrome, a requirement for intravenous (IV) alimentation, prior surgical procedures affecting absorption, or uncontrolled inflammatory GI disease (e.g., Crohn's, ulcerative colitis)
• Treatment with any agents that interact with cytochrome P450 3A should be avoided and used with caution, if necessary; when possible, patients should be switched to alternative medications; patients requiring anticoagulation should either be switched to a low molecular weight heparin injection or have a very close monitoring of INR, if continued on Coumadin
• Previous (within 5 years of enrollment) or current malignancies at other sites, except adequately treated basal cell or squamous cell skin cancers and carcinoma in situ of the cervix
• Other severe acute or chronic medical or psychiatric conditions or laboratory abnormality that may increase the risk associated with study participation or study drug administration or may interfere with interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for study entry

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (2)

Harper University Hospital - DMC

Detroit, Michigan, 48201, United States

Location

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

MeSH Terms

Conditions

Breast Neoplasms, Male; Breast Neoplasms

Interventions

Lapatinib; Tamoxifen

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Limitations and Caveats

The main limitation in this study was poor enrollment. The small number of cases makes the interpretation of results difficult.

Results Point of Contact

• Title: Sayeh Lavasani, M.D.
• Organization: Barbara Ann Karmanos Cancer Institute

lavasans@karmanos.org

(313) 576-8751

Study Officials

• Elaina Gartner

  Barbara Ann Karmanos Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2005
• First Posted: July 11, 2005
• Study Start: May 1, 2005
• Primary Completion: July 1, 2011
• Study Completion: September 1, 2014
• Last Updated: December 4, 2017
• Results First Posted: December 3, 2014

Record last verified: 2017-10

Locations

US (2)