Lapatinib and Radiation Therapy in Treating Patients With Locally Recurrent or Chemotherapy-Refractory Locally Advanced or Metastatic Breast Cancer

NCT00379509 | Completed Phase 1 DMC

• 2 other identifiers: LCCC 0411P30CA016086
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving lapatinib together with radiation therapy may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of lapatinib when given together with radiation therapy in treating patients with locally recurrent or chemotherapy-refractory locally advanced or metastatic breast cancer.

Conditions

Breast Cancer

Keywords

recurrent breast cancer; stage IIIA breast cancer; stage IIIB breast cancer; stage IIIC breast cancer; stage IV breast cancer; male breast cancer

Outcome Measures

Primary Outcomes (2)

• Toxicity as assessed by NCI CTCAE v3.0

  4-5 years

• Inhibition of receptor and downstream signal transduction pathway activation in tumor tissue as assessed by IHC

  4-5 years

Secondary Outcomes (3)

• Efficacy

  4-5 years

• Correlation of response with inhibition of downstream signaling

  4-5 years

• Gene expression

  4-5 years

Study Arms (1)

GW572016

EXPERIMENTAL

Drug: lapatinib ditosylate; Genetic: TdT-mediated dUTP nick end labeling assay; Genetic: gene expression analysis; Genetic: microarray analysis; Other: immunohistochemistry staining method; Procedure: biopsy; Radiation: radiation therapy

Interventions

lapatinib ditosylate DRUG

Patients will be assigned in cohorts of 3. Dose levels of GW572106 will include 500mg, 1000mg,1500 mg (additional levels at 750 mg and 1250 mg will be added if needed). Lapatinib is an oral drug. It is taken every day.

GW572016

TdT-mediated dUTP nick end labeling assay GENETIC

Genetic analysis of tumor tissue

GW572016

gene expression analysis GENETIC

Genetic analysis of tumor tissue.

GW572016

microarray analysis GENETIC

Genetic analysis of tumor tissue.

GW572016

immunohistochemistry staining method OTHER

Laboratory analysis of tumor tissue.

GW572016

biopsy PROCEDURE

Serial biopsies by skin punch or core biopsy or fine needle aspiration.

GW572016

radiation therapy RADIATION

Radiotherapy will be delivered at standard dose and fractionation. For patients who have not received previous locoregional radiotherapy, 50-56 Gy will be delivered to the regional lymph nodes and/or chest wall at a dose of 2 Gy per fraction, 5 days per week followed by a boost to the sites of gross involvement to a total dose of 60-70 Gy over a course of 6-7 weeks. For patients who have received adjuvant radiotherapy, a dose of 35-45 Gy will be delivered to sites of chest wall involvement at a dose of 1.8 Gy per fraction over 4-5 weeks. In either de novo or reirradiated settings, the total dose to the brachial plexus will not exceed 60 Gy.

GW572016

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Diagnosis of breast cancer meeting 1 of the following criteria: * Locally recurrent disease * Locally advanced disease AND meets the following criterion: * Chemotherapy-refractory disease (achieved \< partial response to ≥ 3 courses of neoadjuvant chemotherapy) * Metastatic disease * Evaluable disease by exam and/or imaging studies * Amenable to serial biopsies by skin punch, core biopsy, or fine-needle aspiration * Unresectable disease after standard neoadjuvant chemotherapy * Resectability must be determined by a surgical oncologist prior to treatment * Stable CNS metastases allowed * Hormone receptor status not specified PATIENT CHARACTERISTICS: * Male or female * Menopausal status not specified * Life expectancy \> 12 weeks * ECOG performance status 0-2 * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * Able to swallow and retain oral medication * WBC ≥ 3,000/mm³ * ANC ≥ 1,500/mm³ * Platelet count ≥ 100,000/mm³ * Total bilirubin normal * AST and ALT ≤ 2.5 times upper limit of normal * Creatinine normal OR creatinine clearance ≥ 60 mL/min * Cardiac ejection fraction normal by ECHO or MUGA * No other malignancy within the past 5 years * No concurrent disease or condition that would preclude study participation * No ongoing coagulopathy * No active severe infection PRIOR CONCURRENT THERAPY: * See Disease Characteristics * Recovered from prior therapy * At least 3 weeks since prior and no other concurrent systemic therapy for breast cancer * At least 14 days since prior and no concurrent herbal or alternative medicine * At least 14 days since prior and no concurrent dietary supplement * At least 14 days since prior CYP3A4 inducers * At least 7 days since prior CYP3A4 inhibitors * No antacid within 1 hour before or after study drug administration * Concurrent bisphosphonate allowed * No concurrent oral glucocorticosteroid \> 1.5 mg of dexamethasone (or equivalent)

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• UNC Lineberger Comprehensive Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

Chapel Hill, North Carolina, 27599-7295, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Breast Neoplasms, Male

Interventions

Lapatinib; Gene Expression Profiling; Microarray Analysis; Immunohistochemistry; Biopsy; Radiotherapy

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; Genetic Techniques; Investigative Techniques; Microchip Analytical Procedures; Histocytochemistry; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Histological Techniques; Immunologic Techniques; Cytodiagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Therapeutics

Study Officials

• Elizabeth C. Dees, MD

  UNC Lineberger Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 20, 2006
• First Posted: September 22, 2006
• Study Start: April 1, 2006
• Primary Completion: June 1, 2010
• Study Completion: August 1, 2012
• Last Updated: March 21, 2017

Record last verified: 2017-03

Locations

US (1)