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

Phase 1/Phase 2
18 Years
Open (Enrolling)
Breast Cancer

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Trial Information

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



- 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

- 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.

Inclusion Criteria


- 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 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


- Menopausal status not specified

- ECOG 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

- Alkaline phosphatase ≤ 2.5 times ULN (≤ 5 times ULN in the presence of liver or bone

- 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

- 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


- 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

Type of Study:


Study Design:

Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum-tolerated dose of bendamustine hydrochloride and erlotinib hydrochloride (phase I)

Safety Issue:


Principal Investigator

Rachel Layman, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Ohio State University Comprehensive Cancer Center


United States: Federal Government

Study ID:




Start Date:

April 2009

Completion Date:

Related Keywords:

  • Breast Cancer
  • male breast cancer
  • recurrent breast cancer
  • stage IIIB breast cancer
  • stage IIIC breast cancer
  • stage IV breast cancer
  • estrogen receptor-negative breast cancer
  • HER2-negative breast cancer
  • progesterone receptor-negative breast cancer
  • triple-negative breast cancer
  • Breast Neoplasms



University of Michigan Comprehensive Cancer Center Ann Arbor, Michigan  48109-0752
Robert H. Lurie Comprehensive Cancer Center at Northwestern University Chicago, Illinois  60611
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center Columbus, Ohio  43210-1240