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

Phase 1

Completed

• Conditions: Breast Cancer
• Interventions: 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

• Registration Number: NCT00379509
• Lead Sponsor: UNC Lineberger Comprehensive Cancer Center

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.

Detailed Description

OBJECTIVES:

Primary

* Determine the toxicity of lapatinib ditosylate and radiotherapy in patients with locally recurrent breast cancer or chemotherapy-refractory, locally advanced or metastatic breast cancer.

* Determine the impact of this drug on inhibition of receptor and downstream signal transduction pathway activation in tumor tissue, in the context of inhibitor dose escalation with or without radiotherapy.

Secondary

* Determine, preliminarily, the efficacy of lapatinib ditosylate and radiotherapy in these patients.

* Correlate response in these patients with inhibition of downstream signaling.

* Assess gene expression changes in tumor biopsy samples from patients treated with lapatinib ditosylate alone or in combination with radiotherapy.

OUTLINE: This is a multicenter, parallel group, dose-escalation study of lapatinib ditosylate. Patients are stratified according to prior radiotherapy (yes vs no).

* Group I (prior radiotherapy): Patients receive oral lapatinib ditosylate once daily in the absence of disease progression or unacceptable toxicity. Beginning on day 8 of lapatinib ditosylate therapy, patients undergo concurrent radiotherapy 5 days a week for up to 5 weeks.

* Group II (no prior radiotherapy): Patients receive oral lapatinib ditosylate as in group I. Beginning on day 8, patients undergo concurrent radiotherapy 5 days a week for up to 7 weeks.

In each group, cohorts of 3-6 patients receive escalating doses of lapatinib ditosylate until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity during the first course.

Patients undergo skin punch or core biopsy at baseline\* and on day 8 and day 15. Tumor biopsy samples are examined by IHC for evaluation of EGFR, phospho-EGFR, HER2, phospho-HER2, phospho-Akt, and phospho-MAPK. Samples are also examined for cell proliferation by Ki-67, apoptosis by TUNEL, and angiogenesis by microvessel density. Additionally, mRNA is extracted from fresh frozen samples and examined by microarray analysis.

NOTE: \*Archival tissue acceptable for baseline sample, if available

Study Timeline

• Study Start: 2006-04
• Study First Submitted: 2006-09-20
• Study First Submitted QC: 2006-09-20
• Study First Posted: 2006-09-22
• Primary Completion: 2010-06
• Study Completion: 2012-08
• Status Verified: 2017-03
• Last Update Submitted: 2017-03-17
• Last Update Posted: 2017-03-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
GW572016	gene expression analysis	-
GW572016	lapatinib ditosylate	-
GW572016	biopsy	-
GW572016	TdT-mediated dUTP nick end labeling assay	-
GW572016	microarray analysis	-
GW572016	immunohistochemistry staining method	-
GW572016	radiation therapy	-

Primary Outcome Measures

Name	Time	Method
Inhibition of receptor and downstream signal transduction pathway activation in tumor tissue as assessed by IHC	4-5 years
Toxicity as assessed by NCI CTCAE v3.0	4-5 years

Secondary Outcome Measures

Name	Time	Method
Gene expression	4-5 years
Efficacy	4-5 years
Correlation of response with inhibition of downstream signaling	4-5 years

Trial Locations

Locations (1)

Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill; 🇺🇸 Chapel Hill, North Carolina, United States