Phase I/II Study of Bendamustine and Erlotinib for Metastatic or Locally Advanced Triple Negative Breast Cancer
18 Years
N/A
Both
Breast Cancer
Trial Information
Phase I/II Study of Bendamustine and Erlotinib for Metastatic or Locally Advanced Triple Negative 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.
Inclusion 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 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 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
Type of Study:
Interventional
Study Design:
Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Maximum-tolerated dose of bendamustine hydrochloride and erlotinib hydrochloride (phase I)
Safety Issue:
Yes
Principal Investigator
Rachel Layman, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Ohio State University Comprehensive Cancer Center
Authority:
United States: Federal Government
Study ID:
CDR0000633771
NCT ID:
NCT00834678
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
Name | Location |
|---|---|
| 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 |
