Bendamustine and Erlotinib in Treating Patients With Stage IIIB, Stage IIIC, or Stage IV Breast Cancer
Information source: National Cancer Institute (NCI)
Information obtained from ClinicalTrials.gov on October 19, 2009
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Breast Cancer
Intervention: bendamustine hydrochloride (Drug); erlotinib hydrochloride (Drug); fluorescence in situ hybridization (Genetic); microarray analysis (Genetic); immunohistochemistry staining method (Other); laboratory biomarker analysis (Other); staining method (Other)
Phase: Phase 1/Phase 2
Status: Recruiting
Sponsored by: Arthur G. James Cancer Hospital & Richard J. Solove Research Institute Official(s) and/or principal investigator(s):
Rachel Layman, MD, Principal Investigator, Affiliation: Arthur G. James Cancer Hospital & Richard J. Solove Research Institute
Rachel Layman, MD, Principal Investigator, Affiliation: Arthur G. James Cancer Hospital & Richard J. Solove Research Institute
Summary
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.
Clinical Details
Official title: Phase I/II Study of Bendamustine and Erlotinib for Metastatic or Locally Advanced Triple Negative Breast Cancer
Study design: Treatment, Open Label
Primary outcome: Maximum-tolerated dose of bendamustine hydrochloride and erlotinib hydrochloride (phase I)Dose-limiting toxicity (phase I) Progression-free survival at 6 months and 12 months (phase II)
Secondary outcome: Objective response rate (ORR)Clinical benefit rate (CBR) Duration of response (DR) Overall survival (OS) rate Relationship of EGFR expression or amplification, basal-like tumors, and DNA damage-repair checkpoint activation with ORR, CBR, DR, and OS
Detailed 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.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
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
Locations and Contacts
Robert H. Lurie Comprehensive Cancer Center at Northwestern University, Chicago, Illinois 60611-3013, United States; Recruiting
Clinical Trials Office - Robert H. Lurie Comprehensive Cancer, Phone: 312-695-1301, Email: cancer@northwestern.edu
University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan 48109-0942, United States; Recruiting
Clinical Trials Office - University of Michigan Comprehensive, Phone: 800-865-1125
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center, Columbus, Ohio 43210-1240, United States; Recruiting
Ohio State University Cancer Clinical Trial Matching Service, Phone: 866-627-7616, Email: osu@emergingmed.com
Additional Information
Clinical trial summary from the National Cancer Institute's PDQ® database
Starting date: April 2009
Last updated: July 10, 2009
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