Symptoms and General Pathology

All Conditions

Neoplasms

Skin and Connective Tissue Diseases

Rare Diseases

Recurrence

Breast Neoplasms

Triple Negative Breast Neoplasms

Breast Neoplasms, Male

Breast Diseases

Skin Diseases

Breast Cancer, Male

All Drugs and Chemicals

Antineoplastic Agents

Amino Acids

Estrogens

Bendamustine Hydrochloride

Progesterone

Erlotinib Hydrochloride

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Antineoplastic Agents, Alkylating

Alkylating Agents

Tyrosine

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.

bendamustine

100 or 150 mg po on days 5 - 21 of each 28 day cycle

erlotinib

150 mg po daily (days 1 - 28 of 28 day cycle)

Maintenance erlotinib

Rachel Layman, MD

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.

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.

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

Phase I/II Study of Bendamustine and Erlotinib for Metastatic or Locally Advanced Triple Negative Breast Cancer

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

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

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

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.

National Comprehensive Cancer Network

Genentech, Inc.

Ohio State University Comprehensive Cancer Center

This study will utilize the CTCAE (NCI Common Terminology Criteria for Adverse Events) Version 3.0 for toxicity and Serious Adverse Event reporting.

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.

bendamustine: 100 or 120 mg/m2 IV on days 1 and 2

erlotinib: 100 or 150 mg po on days 5 - 21 of each 28 day cycle

Maintenance erlotinib: 150 mg po daily (days 1 - 28 of 28 day cycle)

Bendamustine and Erlotinib

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

0 (Fully active)

1 (Restricted)

2 (Ambulatory and capable selfcare)

ECOG (Eastern Cooperative Oncology Group) performance status

Lymph nodes

Lung/pleura

Bone

Liver

Chest wall/skin

Brain

A patient can be represented among multiple sites

Site of metastasis

Adjuvant only

Metastasis/local recurrence only

Both

Prior chemotherapy

1 prior regimen

2 prior regimens

Total number of prior treatment regimens

Participants in dose level I were administered 100 mg/m\^2 IV of Bendamustine on days 1 and 2 and 100 mg PO of Erlotinib on days 5 - 21 of each 28 day cycle.

Participants in dose level II were administered 120 mg/m\^2 IV of Bendamustine on days 1 and 2 and 150 mg PO of Erlotinib on days 5 - 21 of each 28 day cycle.

Maximum-tolerated Dose of Bendamustine Hydrochloride (Phase I)

Maximum-tolerated Dose of Erlotinib Hydrochloride (Phase I)

Dose level I, n=5

Dose level II, n=6

Dose-limiting Toxicity (Phase I)

Progression-free Survival at 6 Months and 12 Months (Phase II)

Dose Level 1

Dose Level 2

Objective Response Rate (ORR)

Patients in dose level I were administered Bendamustine 100 or 120 mg/m2 IV on days 1 and 2 and 100 mg PO of Erlotinib on days 5 - 21 of each 28 day cycle.

Clinical Benefit Rate (CBR)

Duration of Response (DR)

Overall Survival (OS)

Correlative studies to assess EGFR expression and gene amplification, were planned, but not collected because of early trial termination.

Relationship of EGFR Expression or Amplification, Basal-like Tumors, and DNA Damage-repair Checkpoint Activation With ORR, CBR, DR, and OS

Overall Study

Spots Global Cancer Trial Database for maintenance erlotinib