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Bendamustine and Erlotinib in Treating Patients With Stage IIIB, Stage IIIC, or Stage IV Breast Cancer

Phase 1
Completed
Conditions
Breast Cancer
Interventions
Registration Number
NCT00834678
Lead Sponsor
Ohio State University Comprehensive Cancer Center
Brief Summary

RATIONALE: Drugs used in chemotherapy, such as bendamustine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving bendamustine together with erlotinib may kill more tumor cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of giving bendamustine together with erlotinib in treating patients with stage IIIB, stage IIIC, or stage IV breast cancer.

Detailed Description

OBJECTIVES:

Primary

* To determine the phase II dose and assess the toxicity of bendamustine hydrochloride and erlotinib hydrochloride in patients with triple-receptor (estrogen receptor, progesterone receptor, and HER-2)-negative, stage IIIB, IIIC, or IV breast cancer. (Phase I)

* To determine the efficacy of this regimen in these patients. (Phase II)

Secondary (Correlative)

* To assess the correlation between tumor EGFR expression and EGFR gene amplification and treatment efficacy and toxicity.

* To assess for differences in treatment efficacy between basal-like and non-basal-like cancers.

* To assess for differences in treatment efficacy between tumors with and without expression of DNA damage-response (DDR) checkpoint proteins.

* To assess for differences in the activation state of DDR checkpoint proteins based on breast cancer subtype.

OUTLINE: This is a multicenter, phase I dose-escalation study followed by a phase II study.

Patients receive bendamustine hydrochloride IV over 30 minutes on days 1-2 and oral erlotinib hydrochloride once daily on days 5-21. Treatment repeats every 28 days for at least 6 courses in the absence of disease progression or unacceptable toxicity.

Patients with no evidence of disease progression may continue with daily single-agent oral erlotinib hydrochloride on days 1-28. Treatment continues every 28 days in the absence of disease progression or unacceptable toxicity.

Breast cancer tissue blocks from prior procedures are obtained for correlative studies. After a tissue microarray (TMA) and a TMA map are prepared, TMA slides are used for hematoxylin and eosin (H\&E) staining, FISH, and IHC.

After completion of study treatment, patients are followed every 3 months for 2 years.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
11
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Bendamustine and ErlotinibMaintenance erlotinibBendamustine 100 or 120 mg/m2 IV on days 1 and 2 and erlotinib 100 or 150 mg po on days 5 - 21 of each 28 day cycle.
Bendamustine and ErlotinibbendamustineBendamustine 100 or 120 mg/m2 IV on days 1 and 2 and erlotinib 100 or 150 mg po on days 5 - 21 of each 28 day cycle.
Bendamustine and ErlotiniberlotinibBendamustine 100 or 120 mg/m2 IV on days 1 and 2 and erlotinib 100 or 150 mg po on days 5 - 21 of each 28 day cycle.
Primary Outcome Measures
NameTimeMethod
Maximum-tolerated Dose of Bendamustine Hydrochloride (Phase I)Up to two years

28 day cycle included intravenous bendamustine on days 1 and 2.

Maximum-tolerated Dose of Erlotinib Hydrochloride (Phase I)Up to two years

28 day cycle included intravenous erlotinib on days 15-21.

Dose-limiting Toxicity (Phase I)Up to two years
Progression-free Survival at 6 Months and 12 Months (Phase II)Up to two years

Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

Secondary Outcome Measures
NameTimeMethod
Objective Response Rate (ORR)Up to two years

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Clinical Benefit Rate (CBR)Up to two years
Duration of Response (DR)Up to two years
Overall Survival (OS)from time of study enrollment until death, for up to 2 years
Relationship of EGFR Expression or Amplification, Basal-like Tumors, and DNA Damage-repair Checkpoint Activation With ORR, CBR, DR, and OSup to two years

Trial Locations

Locations (1)

Ohio State University Medical Center

🇺🇸

Columbus, Ohio, United States

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