Bendamustine and Erlotinib in Treating Patients With Stage IIIB, Stage IIIC, or Stage IV Breast Cancer
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.
|Breast Cancer||Drug: bendamustine Drug: erlotinib Drug: Maintenance erlotinib||Phase 1 Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I/II Study of Bendamustine and Erlotinib for Metastatic or Locally Advanced Triple Negative Breast Cancer|
- Maximum-tolerated Dose of Bendamustine Hydrochloride (Phase I) [ Time Frame: Up to two years ]28 day cycle included intravenous bendamustine on days 1 and 2.
- Maximum-tolerated Dose of Erlotinib Hydrochloride (Phase I) [ Time Frame: Up to two years ]28 day cycle included intravenous erlotinib on days 15-21.
- Dose-limiting Toxicity (Phase I) [ Time Frame: Up to two years ]
- Progression-free Survival at 6 Months and 12 Months (Phase II) [ Time Frame: 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
- Objective Response Rate (ORR) [ Time Frame: 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) [ Time Frame: Up to two years ]
- Duration of Response (DR) [ Time Frame: Up to two years ]
- Overall Survival (OS) Rate [ Time Frame: 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 OS [ Time Frame: up to two years ]
|Study Start Date:||April 2009|
|Study Completion Date:||September 2014|
|Primary Completion Date:||August 2013 (Final data collection date for primary outcome measure)|
Experimental: Bendamustine and Erlotinib
Bendamustine 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.
100 or 120 mg/m2 IV on days 1 and 2
Other Names:Drug: erlotinib
100 or 150 mg po on days 5 - 21 of each 28 day cycle
Other Name: TarcevaDrug: Maintenance erlotinib
150 mg po daily (days 1 - 28 of 28 day cycle)
Other Name: Tarceva
- 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)
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00834678
|United States, Ohio|
|Ohio State University Medical Center|
|Columbus, Ohio, United States, 43210|
|Principal Investigator:||Rachel Layman, MD||Ohio State University Comprehensive Cancer Center|