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

The Ohio State University

Status and phase

Completed

Phase 2

Phase 1

Conditions

Breast Cancer

Treatments

Drug: Maintenance erlotinib

Drug: erlotinib

Drug: bendamustine

Study type

Interventional

Funder types

Other

NETWORK

Industry

Identifiers

NCT00834678

OSU-08164

NCI-2011-03164 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment

11 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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