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

This study has been completed.
National Comprehensive Cancer Network
Genentech, Inc.
Information provided by (Responsible Party):
Rachel Layman, Ohio State University Comprehensive Cancer Center Identifier:
First received: January 31, 2009
Last updated: May 1, 2015
Last verified: May 2015

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
Drug: erlotinib
Drug: Maintenance erlotinib
Phase 1
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Study of Bendamustine and Erlotinib for Metastatic or Locally Advanced Triple Negative Breast Cancer

Resource links provided by NLM:

Further study details as provided by Ohio State University Comprehensive Cancer Center:

Primary Outcome Measures:
  • Maximum-tolerated Dose of Bendamustine Hydrochloride (Phase I) [ Time Frame: Up to two years ]
    28 day cycle included intravenous bendamustine on days 1 and 2.

  • Maximum-tolerated Dose of Erlotinib Hydrochloride (Phase I) [ Time Frame: Up to two years ]
    28 day cycle included intravenous erlotinib on days 15-21.

  • Dose-limiting Toxicity (Phase I) [ Time Frame: Up to two years ]
  • Progression-free Survival at 6 Months and 12 Months (Phase II) [ Time Frame: Up to two years ]
    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

Secondary Outcome Measures:
  • Objective Response Rate (ORR) [ Time Frame: Up to two years ]
    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.

  • Clinical Benefit Rate (CBR) [ Time Frame: Up to two years ]
  • Duration of Response (DR) [ Time Frame: Up to two years ]
  • Overall Survival (OS) Rate [ Time Frame: 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 [ Time Frame: up to two years ]

Enrollment: 11
Study Start Date: April 2009
Study Completion Date: September 2014
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Bendamustine and Erlotinib
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
100 or 120 mg/m2 IV on days 1 and 2
Other Names:
  • Ribomustin
  • Treanda
  • SDX- 105
Drug: erlotinib
100 or 150 mg po on days 5 - 21 of each 28 day cycle
Other Name: Tarceva
Drug: Maintenance erlotinib
150 mg po daily (days 1 - 28 of 28 day cycle)
Other Name: Tarceva

Detailed Description:



  • 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.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • 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


  • 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


  • 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00834678

United States, Ohio
Ohio State University Medical Center
Columbus, Ohio, United States, 43210
Sponsors and Collaborators
Rachel Layman
National Comprehensive Cancer Network
Genentech, Inc.
Principal Investigator: Rachel Layman, MD Ohio State University Comprehensive Cancer Center
  More Information

Additional Information:
Responsible Party: Rachel Layman, Principal Investigator, Ohio State University Comprehensive Cancer Center Identifier: NCT00834678     History of Changes
Other Study ID Numbers: OSU-08164
NCI-2011-03164 ( Registry Identifier: Clinical Trial Reporting Program (CTRP) )
Study First Received: January 31, 2009
Results First Received: September 26, 2014
Last Updated: May 1, 2015

Keywords provided by Ohio State University Comprehensive Cancer Center:
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

Additional relevant MeSH terms:
Breast Neoplasms
Triple Negative Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Erlotinib Hydrochloride
Bendamustine Hydrochloride
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Alkylating
Alkylating Agents processed this record on May 22, 2017