Clinical trial NCT01891227: Capecitabine + Bendamustine in Women With Pretreated Locally Advanced or Metastatic Her2-negative Breast Cancer
Official title: Capecitabine in Combination With Bendamustine in Women With Pretreated Locally Advanced or Metastatic Her2-negative Breast Cancer, a Phase II Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: Bendamustine
Capecitabine
Pretreated
Her2 negative
Advanced breast cancer
Metastatic breast cancer
Anthracycline pretreatment
Taxane pretreatment
Lead sponsor: Arbeitsgemeinschaft medikamentoese Tumortherapie
Sponsor class: OTHER
First posted: 2013-07-03
Enrollment: 40
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Efficacy of capecitabine + bendamustine combination regimen
timeFrame: At baseline + every 9 weeks until progression + at end of study treatment; expected study duration 3 years
Secondary outcomes:
measure: Safety profile of a combination with capecitabine and bendamustine
timeFrame: From treatment start until 28 days after last study treatment; expected study duration 3 years
measure: Clinical benefit
timeFrame: Baseline + every 9 weeks until progression + at end of study treatment; expected study duration 3 years
measure: Progression free survival
timeFrame: Baseline + every 9 weeks until progression; expected study duration 3 years
measure: Overall survival
timeFrame: During complete study treatment, after study treatment every 3 months until end of complete study; expected study duration 3 years
measure: Quality of life
timeFrame: Baseline + every 9 weeks until progression + at end of study treatment; expected study duration 3 years
measure: Predefined subgroup analysis in terms of response
timeFrame: 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
Other outcomes:
Locations:
city: Feldkirch
country: Austria
facility: Hämatologie und Onkologie/Interne E, LKH Feldkirch
city: Graz
country: Austria
facility: Universitätsklinik f. Frauenheilkunde und Geburtshilfe, Klin. Abt. f. Gynäkologie
city: Graz
country: Austria
facility: Universitätsklinik f. Innere Medizin, Klin.Abt. f. Onkologie
city: Innsbruck
country: Austria
facility: Univ.-Klinik f. Frauenheilkunde; Klinische Abt. f. Gynäkologie u. Geburtshilfe
city: Linz
country: Austria
facility: KH Barmh. Schwestern Linz, Innere Medizin I Hämatologie/Onkologie
city: Linz
country: Austria
facility: Kepler Universitätsklinikum, Med Campus III, Klinik f. Interne 3 - Schwerpunkt Hämatologie u. Onkologie
city: Salzburg
country: Austria
facility: Universitätsklinik für Innere Medizin III
city: Steyr
country: Austria
facility: Landeskrankenhaus Steyr, Interne Medizin II
Study officials:
affiliation: Universitätsklinik für Innere Medizin III, Salzburg
name: Richard Greil, Prof.Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rinnerthaler G, Gampenrieder SP, Petzer A, Hubalek M, Petru E, Sandholzer M, Andel J, Balic M, Melchardt T, Hauser-Kronberger C, Schmitt CA, Ulmer H, Greil R. Capecitabine in combination with bendamustine in pretreated women with HER2-negative metastatic breast cancer: results of a phase II trial (AGMT MBC-6). Ther Adv Med Oncol. 2021 Oct 19;13:17588359211042301. doi: 10.1177/17588359211042301. eCollection 2021.