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

NCT00834678 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: OSU-08164NCI-2011-03164
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Breast Cancer

Keywords

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

Outcome Measures

Primary Outcomes (4)

• Maximum-tolerated Dose of Bendamustine Hydrochloride (Phase I)

  28 day cycle included intravenous bendamustine on days 1 and 2.

  Up to two years

• Maximum-tolerated Dose of Erlotinib Hydrochloride (Phase I)

  28 day cycle included intravenous erlotinib on days 15-21.

  Up to two years

• Dose-limiting Toxicity (Phase I)

  Up to two years

• 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 Outcomes (5)

• Objective Response Rate (ORR)

  Up to two years

• Clinical Benefit Rate (CBR)

  Up to two years

• Duration of Response (DR)

  Up to two years

• Overall Survival (OS)

  from time of study enrollment until death, for up to 2 years

• 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

Study Arms (1)

Bendamustine and Erlotinib

EXPERIMENTAL

Bendamustine 100 or 120 mg/m2 IV on days 1 and 2 and erlotinib 100 or 150 mg po on days 5 - 21 of each 28 day cycle.

Drug: bendamustine; Drug: erlotinib; Drug: Maintenance erlotinib

Interventions

bendamustine DRUG

100 or 120 mg/m2 IV on days 1 and 2

Also known as: Ribomustin, Treanda, SDX- 105

Bendamustine and Erlotinib

erlotinib DRUG

100 or 150 mg po on days 5 - 21 of each 28 day cycle

Also known as: Tarceva

Bendamustine and Erlotinib

Maintenance erlotinib DRUG

150 mg po daily (days 1 - 28 of 28 day cycle)

Also known as: Tarceva

Bendamustine and Erlotinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Ohio State University Comprehensive Cancer Center: lead
• National Comprehensive Cancer Network: collaborator
• Genentech, Inc.: collaborator

Study Sites (1)

Ohio State University Medical Center

Columbus, Ohio, 43210, United States

Location

Related 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 metastatic triple negative breast cancer. Cancer Chemother Pharmacol. 2013 May;71(5):1183-90. doi: 10.1007/s00280-013-2112-2. Epub 2013 Feb 21.

  PMID: 23430121 RESULT

Related Links

• Jamesline

MeSH Terms

Conditions

Breast Neoplasms; Breast Neoplasms, Male; Triple Negative Breast Neoplasms

Interventions

Bendamustine Hydrochloride; Erlotinib Hydrochloride

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Quinazolines

Results Point of Contact

• Title: Rachel Layman, MD
• Organization: The Ohio State University Comprehensive Cancer Center

Rachel.Layman@osumc.edu

614-366-8541

Study Officials

• Rachel Layman, MD

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 31, 2009
• First Posted: February 3, 2009
• Study Start: April 1, 2009
• Primary Completion: August 1, 2013
• Study Completion: September 1, 2014
• Last Updated: April 17, 2018
• Results First Posted: April 22, 2015

Record last verified: 2018-03

Locations

US (1)