Capecitabine + Bendamustine in Women With Pretreated Locally Advanced or Metastatic Her2-negative Breast Cancer (MBC-6)

Capecitabine in Combination With Bendamustine in Women With Pretreated Locally Advanced or Metastatic Her2-negative Breast Cancer, a Phase II Trial

Patients with pretreated, Her2-negative, advanced breast cancer will receive chemotherapy with capecitabine and bendamustine for a maximum of eight cycles and afterwards capecitabine alone until disease progression or unacceptable toxic effects. Safety assessments will be conducted in 3-weekly intervals, efficacy assessments (CT or MRI) will be conducted every 9 weeks.

Aim of this study is to determine whether treatment with capecitabine in combination with bendamustine is efficacious and safe.

Study Overview

Status

Completed

Conditions

Detailed Description

40 eligible patients will be enrolled. A two-stage design efficacy and safety of bendamustine and capecitabine will be evaluated following recruitment of the first 20 patients. Upon favorable results a further 20 patients will be recruited to reach the target population of 40 evaluable patients.

Pretreatment for eligible patients must include anthracyclines and/or taxanes.

Study Type

Interventional

Enrollment (Actual)

40

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Feldkirch, Austria, A-6807
        • Hämatologie und Onkologie/Interne E, LKH Feldkirch
      • Graz, Austria, 8036
        • Universitätsklinik f. Frauenheilkunde und Geburtshilfe, Klin. Abt. f. Gynäkologie
      • Graz, Austria, 8036
        • Universitätsklinik f. Innere Medizin, Klin.Abt. f. Onkologie
      • Innsbruck, Austria, A-6020
        • Univ.-Klinik f. Frauenheilkunde; Klinische Abt. f. Gynäkologie u. Geburtshilfe
      • Linz, Austria, A-4010
        • KH Barmh. Schwestern Linz, Innere Medizin I Hämatologie/Onkologie
      • Linz, Austria, A-4021
        • Kepler Universitätsklinikum, Med Campus III, Klinik f. Interne 3 - Schwerpunkt Hämatologie u. Onkologie
      • Salzburg, Austria, A-5020
        • Universitätsklinik für Innere Medizin III
      • Steyr, Austria, A-4400
        • Landeskrankenhaus Steyr, Interne Medizin II

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Signed informed consent
  • Female patients, age ≥ 18 years (women of childbearing potential must have a negative pregnancy test at screening and must use effective contraception)
  • Advanced or metastatic Her2-negative breast cancer, histologically confirmed
  • At least one measurable lesion according to RECIST criteria (Version 1.1)
  • Documented disease progression
  • Patients with progression after anthracycline and/or taxane treatment(palliative or adjuvant)
  • Life expectancy of at least 12 weeks
  • Performance status 0-2
  • Hematologic:

    • ANC (absolute neutrophil count) ≥ 1.5 x 109/L
    • Hemoglobin ≥ 9 g/dL
    • Platelets ≥ 100 x 109/L
  • Liver Function:

    • Albumin ≥ 2.5 g/dL
    • Serum bilirubin ≤ 2 mg/dL
    • AST (Aspartate aminotransferase) and ALT (Alanine aminotransferase) ≤ 3 x ULN (Upper limit of Normal) without liver metastases

      • 5 x ULN if documented liver metastases
  • Renal Function:
  • Serum Creatinine ≤ 1.5 mg/dL OR Calculated Creatinine Clearance ≥ 40 mL/min

Exclusion Criteria:

  • Pregnant or lactating women
  • Serious medical or psychiatric disorders that would interfere with the patient's safety or informed consent
  • Radiation of the target lesion within the last 4 weeks
  • Active bacterial, viral or fungal infection
  • Patients with clinically apparent brain metastases
  • Known Positivity for HIV
  • Positivity for Hepatitis B or C
  • History of other malignancy; patients who have been disease-free for 5 years or patients with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible.
  • Concurrent cancer therapy (chemotherapy, immunotherapy, antihormonal or biologic therapy) or concurrent treatment with an investigational drug
  • Antihormonal therapy must have been discontinued prior to start of treatment (if possible at least 3 weeks before)
  • Known hypersensitivity to the study drugs capecitabine and bendamustine or their excipients
  • Pretreatment with capecitabine (pretreatment with infusional 5-FU (Fluorouracil) in the adjuvant or neoadjuvant setting is allowed) or bendamustine
  • Treatment with sorivudine or derivates e.g. brivudin (Mevir©) within the last 4 weeks before and during study treatment with capecitabine

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Capecitabine and Bendamustine

Capecitabine will be dosed at 1000mg/m2 twice daily for 14 days, followed by a 7-day rest period for a total cycle time of 21 days (until disease progression or unacceptable toxic effects).

Bendamustine 80mg/m2 will be administered on day 1 and 8 of a three week cycle (for a maximum of eight cycles).

Eligible patients will receive capecitabine in combination with bendamustine for a maximum of eight cycles and afterwards capecitabine mono will be continued until disease progression or unacceptable toxic effects. Safety assessments will be conducted in 3-weekly intervals; efficacy assessments will be conducted every 9 weeks.

Capecitabine will be dosed at 1000mg/m2 twice daily for 14 days, followed by a 7-day rest period for a total cycle time of 21 days (until disease progression or unacceptable toxic effects).
Other Names:
  • Xeloda
Bendamustine 80mg/m2 will be administered on day 1 and 8 of a three week cycle (for a maximum of eight cycles).
Other Names:
  • Levact

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Efficacy of capecitabine + bendamustine combination regimen
Time Frame: At baseline + every 9 weeks until progression + at end of study treatment; expected study duration 3 years

Overall response rates (complete or partial response, determined by radiologic evaluation according to Response Evaluation Criteria in Solid Tumors - RECIST (Response Evaluation Criteria In Solid Tumors) Version 1.1) The study will be stopped after 20 patients if there are fewer than four subjects with an overall response of CR (complete response) or PR (partial response). If there are at least four responses an additional 20 subjects will be enrolled and treated till a maximum of 40 subjects. The regimen is concluded to be effective if 13 or more responses out of 40 are observed at the end of the trial.

The last patient is expected to enter the study in Q1 2015, following a 24 month recruitment period. Last Subject Last Visit will be at final staging after end of treatment of last patient. Follow-up after Last Subject Last Visit will be conducted according to local standard of care thereafter, and is not part of study procedures.

At baseline + every 9 weeks until progression + at end of study treatment; expected study duration 3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety profile of a combination with capecitabine and bendamustine
Time Frame: From treatment start until 28 days after last study treatment; expected study duration 3 years
To determine the safety profile of a combination with capecitabine and bendamustine in terms of qualitative and quantitative toxicities from first study treatment dose until completion of study treatment due to progression or for any other reason. All safety analyses will be based on the safety population, defined as subjects who received at least one dose of the study medication and have at least one post-treatment safety assessment available. The safety population will be used for all safety and tolerability analyses including demographic data, vital signs, laboratory data and adverse events.
From treatment start until 28 days after last study treatment; expected study duration 3 years
Clinical benefit
Time Frame: Baseline + every 9 weeks until progression + at end of study treatment; expected study duration 3 years
CR, PR or stable disease for at least 24 weeks
Baseline + every 9 weeks until progression + at end of study treatment; expected study duration 3 years
Progression free survival
Time Frame: Baseline + every 9 weeks until progression; expected study duration 3 years
Baseline + every 9 weeks until progression; expected study duration 3 years
Overall survival
Time Frame: During complete study treatment, after study treatment every 3 months until end of complete study; expected study duration 3 years
explorative, from treatment start until death from any cause
During complete study treatment, after study treatment every 3 months until end of complete study; expected study duration 3 years
Quality of life
Time Frame: Baseline + every 9 weeks until progression + at end of study treatment; expected study duration 3 years
To evaluate Quality of Life (QoL) status within the study population using the EORTC (European Organisation for Research and Treatment of Cancer) QLQ (Quality-of-life-questionnaire)-C30 standard questionnaire and the BR23 module (module for breast cancer patients)
Baseline + every 9 weeks until progression + at end of study treatment; expected study duration 3 years
Predefined subgroup analysis in terms of response
Time Frame: Baseline + every 9 weeks until progression + at end of study treatment+every 3 months after end of treatment until end of study; expected study duration 3 years
Predefined subgroup analysis of triple-negative patients and hormone receptor positive patients in terms of response
Baseline + every 9 weeks until progression + at end of study treatment+every 3 months after end of treatment until end of study; expected study duration 3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Richard Greil, Prof.Dr., Universitätsklinik für Innere Medizin III, Salzburg

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 9, 2013

Primary Completion (Actual)

March 15, 2018

Study Completion (Actual)

March 15, 2018

Study Registration Dates

First Submitted

June 27, 2013

First Submitted That Met QC Criteria

June 28, 2013

First Posted (Estimate)

July 3, 2013

Study Record Updates

Last Update Posted (Actual)

November 7, 2018

Last Update Submitted That Met QC Criteria

November 6, 2018

Last Verified

November 1, 2018

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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