Bendamustine and Erlotinib in Treating Patients With Stage IIIB, Stage IIIC, or Stage IV Breast Cancer - Full Text View

Sponsors and Collaborators:	Arthur G. James Cancer Hospital & Richard J. Solove Research Institute National Cancer Institute (NCI) National Comprehensive Cancer Network
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00834678

Purpose

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.

Condition	Intervention	Phase
Breast Cancer	Drug: bendamustine hydrochloride Drug: erlotinib hydrochloride Genetic: fluorescence in situ hybridization Genetic: microarray analysis Other: immunohistochemistry staining method Other: laboratory biomarker analysis Other: staining method	Phase I Phase II

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer

Drug Information available for: Bendamustine Erlotinib hydrochloride Erlotinib Bendamustine hydrochloride

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	Phase I/II Study of Bendamustine and Erlotinib for Metastatic or Locally Advanced Triple Negative Breast Cancer

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Maximum-tolerated dose of bendamustine hydrochloride and erlotinib hydrochloride (phase I) [ Designated as safety issue: Yes ]
Dose-limiting toxicity (phase I) [ Designated as safety issue: Yes ]
Progression-free survival at 6 months and 12 months (phase II) [ Designated as safety issue: No ]

Secondary Outcome Measures:

Objective response rate (ORR) [ Designated as safety issue: No ]
Clinical benefit rate (CBR) [ Designated as safety issue: No ]
Duration of response (DR) [ Designated as safety issue: No ]
Overall survival (OS) rate [ Designated as safety issue: No ]
Relationship of EGFR expression or amplification, basal-like tumors, and DNA damage-repair checkpoint activation with ORR, CBR, DR, and OS [ Designated as safety issue: No ]

Estimated Enrollment:	57
Study Start Date:	April 2009
Estimated Primary Completion Date:	January 2012 (Final data collection date for primary outcome measure)

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

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00834678

Locations

United States, Illinois
Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Recruiting
Chicago, Illinois, United States, 60611-3013
Contact: Clinical Trials Office - Robert H. Lurie Comprehensive Cancer 312-695-1301 cancer@northwestern.edu
United States, Michigan
University of Michigan Comprehensive Cancer Center	Recruiting
Ann Arbor, Michigan, United States, 48109-0942
Contact: Clinical Trials Office - University of Michigan Comprehensive 800-865-1125
United States, Ohio
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center	Recruiting
Columbus, Ohio, United States, 43210-1240
Contact: Ohio State University Cancer Clinical Trial Matching Service 866-627-7616 osu@emergingmed.com

Sponsors and Collaborators

Arthur G. James Cancer Hospital & Richard J. Solove Research Institute

National Cancer Institute (NCI)

National Comprehensive Cancer Network

Investigators

Principal Investigator:	Rachel Layman, MD	Arthur G. James Cancer Hospital & Richard J. Solove Research Institute
Principal Investigator:	Rachel Layman, MD	Arthur G. James Cancer Hospital & Richard J. Solove Research Institute

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center ( Rachel Layman )
Study ID Numbers:	CDR0000633771, OSU-08164, 2008C0131, NCCN-C03
Study First Received:	January 31, 2009
Last Updated:	April 28, 2009
ClinicalTrials.gov Identifier:	NCT00834678 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

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

Study placed in the following topic categories:

Erlotinib
Estrogens
Skin Diseases
Progesterone
Breast Neoplasms
Breast Cancer, Male
Protein Kinase Inhibitors
Recurrence

Breast Neoplasms, Male
Mechlorethamine
Antineoplastic Agents, Alkylating
Alkylating Agents
Breast Diseases
Nitrogen Mustard Compounds
Bendamustine

Additional relevant MeSH terms:

Erlotinib
Molecular Mechanisms of Pharmacological Action
Skin Diseases
Antineoplastic Agents
Breast Neoplasms
Enzyme Inhibitors
Protein Kinase Inhibitors
Pharmacologic Actions

Neoplasms
Neoplasms by Site
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Breast Diseases
Nitrogen Mustard Compounds
Bendamustine

ClinicalTrials.gov processed this record on May 07, 2009