Bendamustine and 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.

DISEASE CHARACTERISTICS:

• Histologically confirmed breast cancer meeting 1 of the following criteria:

• Unresectable stage IIIB or IIIC disease
• Stage IV disease
• Must be negative for all of the following:

• Estrogen receptor (< 10%)
• Progesterone receptor (<10%)
• HER-2 (negative FISH, IHC 0 - 1+, or IHC +2 with negative FISH)
• Measurable or evaluable disease
• No symptomatic or progressive CNS (central nervous system) metastases

• Previously treated CNS metastases allowed provided all of the following criteria are met:

• At least 8 weeks since prior radiation to brain or CNS metastases
• No concurrent steroids
• No leptomeningeal disease

PATIENT CHARACTERISTICS:

• Menopausal status not specified
• ECOG (Eastern Cooperative Oncology Group) performance status 0-2
• Life expectancy ≥ 6 months
• WBC > 1,500/mm³
• Platelet count > 100,000/mm³
• Creatinine clearance > 40 mL/min
• Normal electrolytes (i.e., Na, K, and Ca normal; minor deviations are allowed if they do not impact on patient safety in the clinical judgment of the treating physician)
• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• ALT and AST ≤ 2.5 times ULN (≤ 5 times ULN in the presence of documented liver metastases)
• Alkaline phosphatase ≤ 2.5 times ULN (≤ 5 times ULN in the presence of liver or bone metastases)
• Not pregnant or nursing
• Fertile patients must use effective barrier contraception
• No uncontrolled intercurrent illness
• No active infection requiring systemic therapy
• Able to swallow oral medications and with no medical problems or prior surgeries that may interfere with the absorption of oral medications including the following:

• Uncontrolled nausea, vomiting, or diarrhea
• Lack of the physical integrity of the upper gastrointestinal tract
• Malabsorption syndrome
• No known hypersensitivity to bendamustine hydrochloride, mannitol, or erlotinib hydrochloride
• No prior malignancy in the past 5 years except for adequately treated basal cell or squamous cell skin carcinoma, or adequately treated stage I-II cancer for which the patient is in complete remission

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Prior adjuvant or neoadjuvant chemotherapy and 1 prior chemotherapy regimen in the metastatic setting allowed provided recovered from all acute toxicities
• No prior bendamustine hydrochloride or EGFR-directed therapy
• No other concurrent antineoplastic treatments, including radiotherapy, chemotherapy, biological therapy, hormonal therapy, immunotherapy, gene therapy, and surgery

• Intravenous bisphosphonates allowed
• No concurrent antiretroviral therapy for HIV-positive patients
• No other concurrent investigational agents