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Phase I Radiosensitization Study of GW572016 With Biologic Correlates in Locoregionally Recurrent Breast Cancer


Phase 1
18 Years
N/A
Not Enrolling
Both
Breast Cancer

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Trial Information

Phase I Radiosensitization Study of GW572016 With Biologic Correlates in Locoregionally Recurrent Breast Cancer


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

Inclusion Criteria


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)

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Toxicity as assessed by NCI CTCAE v3.0

Outcome Time Frame:

4-5 years

Safety Issue:

Yes

Principal Investigator

Elizabeth C. Dees, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

UNC Lineberger Comprehensive Cancer Center

Authority:

United States: Federal Government

Study ID:

LCCC 0411

NCT ID:

NCT00379509

Start Date:

April 2006

Completion Date:

August 2012

Related Keywords:

  • Breast Cancer
  • recurrent breast cancer
  • stage IIIA breast cancer
  • stage IIIB breast cancer
  • stage IIIC breast cancer
  • stage IV breast cancer
  • male breast cancer
  • Breast Neoplasms

Name

Location

Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel HillChapel Hill, North Carolina  27599-7570