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RiTa-Trial - English summary - RiTa

A multicentre phase I-II study to investigate the combination of bendamustine with weekly paclitaxel as first or second line therapy in patients with metastatic breast cancer

Current Status

Phase I: final analysis
Phase II: open

Trial design

Prospective, multi-centre, sequential phase I-II study
Treatment

Phase II: bendamustine 70 mg/m² and paclitaxel 90 mg/m² on days 1, 8 and 15 of a 4 week cycle for 6 months.


Patient population

Inclusion criteria

  1. Written informed consent must be obtained and documented according to the local regulatory requirements prior to beginning specific protocol procedures;
  2. Pathological confirmed primary carcinoma of the breast.
  3. Locally advanced or metastatic disease
  4. Up to one previous palliative chemotherapy that did not contain docetaxel or paclitaxel. Previous adjuvant treatment with taxanes is allowed when the last application of the taxane was given at least 1 year before entering the trial.
  5. Patients must have either measurable or non-measurable lesions according to the WHO criteria
  6. At least 4 weeks since radiotherapy, with full recovery. The measurable disease must be completely outside the radiated field or there must be pathological proof of progressive disease.
  7. Complete radiological and clinical tumor assessment within 4 weeks prior to registration performed as clinically indicated
  8. Karnofsky-Index ≥ 60 %
  9. Age ≥ 18 years
  10. Absolute neutrophil count ≥ 1,500 cells/µl, platelets ≥ 100,000/µl, and haemoglobin ≥ 9 g/dl
  11. Bilirubin within normal limits; evaluation of transaminases and alkaline phosphatase ≤ 5x upper normal limit
  12. Serum creatinine ≤ 2.0 mg/dl
  13. Normal left ventricular ejection fraction (LVEF) by echocardiogramme
  14. Patients of childbearing potential, pregnancy test must be negative
  15. If fertile effective contraception must be used throughout the study

Primary Objective

To determine the maximum tolerated dose of the combination of bendamustine and weekly paclitaxel (phase I part). To determine the progression-free survival achievable with the recommended dose of this combination (phase II part)

Secondary Objectives

  1. To determine the objective response rate (phase II part)
  2. To determine the safety and tolerability of the combination
  3. To determine the dose-limiting toxicity (DLT) (grade IV haematological toxicities or grade III non-haematological toxicities) (phase I part)

Primary Endpoints

part I: maximal tolerated dose
part II: progression-free survival

Study Report

The aim of the study is to establish a feasible combination of bendamustine and paclitaxel in a weekly schedule. The two agents have different toxicity profiles and are well tolerated when given in a weekly fashion. The combination might be of special interest for elderly patients with hormone insensitive tumours. Uptil now for elderly patients there are only data available on monotherapies with paclitaxel, capecitabine and vinorelbine. So far there are no data on the combination of the two agents neither as weekly nor as conventional schedule. However, new combinations might enhance the remission rate and the progression free survival. First results have been presented at Deutsche Krebsgesellschaft (DKG) in 2008.

Reference

von Minckwitz G.; Chernozemsky,I.; Sirakova,L.; Chilingirov,P.; Souchon,R.; Marschner,N.; Kleeberg,U.; Tsekov,C.; Fritze,D.; Thomssen,C.; Stuart,N.; Vermorken,J.B.; Loibl,S.; Merkle,Kh; Kaufmann M., Bendamustine prolongs progression- free survival in metastatic breast cancer (MBC): a phase III prospective, randomized, multicenter trial of bendamustine hydrochloride, methotrexate and 5-fluorouracil (BMF) versus cyclophosphamide, methotrexate and 5-fluorouracil (CMF) as first-line treatment of MBC, Anticancer drugs 16:871-877, 2005

Sibylle Loibl · Caroline Murmann · Katrin Schwedler · Mathias Warm · Lothar Müller · Georg Heinrich · Valentina Nekljudova · Gunter von Minckwitz: Phase I dose Fnding study evaluating the combination of bendamustine with weekly paclitaxel in patients with pre-treated metastatic breast cancer: RiTa trial. Cancer Chemother Pharmacol, Published online: 21 August 2008, DOI: 10.1007/s00280-008-0821-8
  • Study Group: German Breast Group
  • Study Chair: PD Dr. Sibylle Loibl
  • Clinical Project Management: Dr. Silke Weykam
  • Data Management / Biometry: Dr. Valentina Nekljudova
  • Enrollment period: Phase I: closed, Phase II: QIII 2008 – QII 2009
  • Proposed accrual: Phase I: 6-18; Phase II: 42
  • Current accrual: Phase I: 18; Phase II: -
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