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

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ClinicalTrials.gov Identifier: NCT00834678
Recruitment Status : Completed
First Posted : February 3, 2009
Results First Posted : April 22, 2015
Last Update Posted : April 17, 2018
Sponsor:
Collaborators:
National Comprehensive Cancer Network
Genentech, Inc.
Information provided by (Responsible Party):
Ohio State University Comprehensive Cancer Center

Tracking Information
First Submitted Date  ICMJE January 31, 2009
First Posted Date  ICMJE February 3, 2009
Results First Submitted Date  ICMJE September 26, 2014
Results First Posted Date  ICMJE April 22, 2015
Last Update Posted Date April 17, 2018
Actual Study Start Date  ICMJE April 2009
Actual Primary Completion Date August 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 31, 2015)
  • 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
Original Primary Outcome Measures  ICMJE
 (submitted: January 31, 2009)
  • Maximum-tolerated dose of bendamustine hydrochloride and erlotinib hydrochloride (phase I)
  • Dose-limiting Toxicity (Phase I)
  • Progression-free survival (PFS) at 6 months and 12 months (Phase II)
Change History Complete list of historical versions of study NCT00834678 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 19, 2018)
  • 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) [ 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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: January 31, 2009)
  • 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
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Bendamustine and Erlotinib in Treating Patients With Stage IIIB, Stage IIIC, or Stage IV Breast Cancer
Official Title  ICMJE Phase I/II Study of Bendamustine and Erlotinib for Metastatic or Locally Advanced Triple Negative Breast Cancer
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.

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Breast Cancer
Intervention  ICMJE
  • 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
Study Arms  ICMJE 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.
Interventions:
  • Drug: bendamustine
  • Drug: erlotinib
  • Drug: Maintenance erlotinib
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 19, 2013)
11
Original Estimated Enrollment  ICMJE
 (submitted: January 31, 2009)
57
Actual Study Completion Date  ICMJE September 2014
Actual Primary Completion Date August 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00834678
Other Study ID Numbers  ICMJE OSU-08164
NCI-2011-03164 ( Registry Identifier: Clinical Trial Reporting Program (CTRP) )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Ohio State University Comprehensive Cancer Center
Study Sponsor  ICMJE Ohio State University Comprehensive Cancer Center
Collaborators  ICMJE
  • National Comprehensive Cancer Network
  • Genentech, Inc.
Investigators  ICMJE
Principal Investigator: Rachel Layman, MD Ohio State University Comprehensive Cancer Center
PRS Account Ohio State University Comprehensive Cancer Center
Verification Date March 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP