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

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00834678
• Other study ID #: OSU-08164
• Secondary ID: NCI-2011-03164
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: January 31, 2009
• Last updated: March 19, 2018
• Start date: April 2009
• Est. completion date: September 2014

Study information

• Verified date: March 2018
• Source: Ohio State University Comprehensive Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 11
• Est. completion date: September 2014
• Est. primary completion date: August 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Triple Negative Breast Neoplasms

Intervention

Drug:
• bendamustine
100 or 120 mg/m2 IV on days 1 and 2
• erlotinib
100 or 150 mg po on days 5 - 21 of each 28 day cycle
• Maintenance erlotinib
150 mg po daily (days 1 - 28 of 28 day cycle)

Locations

Country	Name	City	State
United States	Ohio State University Medical Center	Columbus	Ohio

Sponsors (3)

Lead Sponsor	Collaborator
Ohio State University Comprehensive Cancer Center	Genentech, Inc., National Comprehensive Cancer Network

Country where clinical trial is conducted

United States, 

References & Publications (1)

Layman RM, Ruppert AS, Lynn M, Mrozek E, Ramaswamy B, Lustberg MB, Wesolowski R, Ottman S, Carothers S, Bingman A, Reinbolt R, Kraut EH, Shapiro CL. Severe and prolonged lymphopenia observed in patients treated with bendamustine and erlotinib for metastat — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum-tolerated Dose of Bendamustine Hydrochloride (Phase I)	28 day cycle included intravenous bendamustine on days 1 and 2.	Up to two years
Primary	Maximum-tolerated Dose of Erlotinib Hydrochloride (Phase I)	28 day cycle included intravenous erlotinib on days 15-21.	Up to two years
Primary	Dose-limiting Toxicity (Phase I)		Up to two years
Primary	Progression-free Survival at 6 Months and 12 Months (Phase II)	Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions	Up to two years
Secondary	Objective Response Rate (ORR)	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.	Up to two years
Secondary	Clinical Benefit Rate (CBR)		Up to two years
Secondary	Duration of Response (DR)		Up to two years
Secondary	Overall Survival (OS)		from time of study enrollment until death, for up to 2 years
Secondary	Relationship of EGFR Expression or Amplification, Basal-like Tumors, and DNA Damage-repair Checkpoint Activation With ORR, CBR, DR, and OS		up to two years

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