Clinical Study

Multicenter, randomised, open-label, non-comparative phase 2 trial on the efficacy and safety of the combination of bevacizumab and trabectedin with or without carboplatin in women with partially platinum-sensitive recurrent ovarian cancer

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Abstract

Background

Trabectedin, in addition to its antiproliferative effect, can modify the tumour microenvironment and this could be synergistic with bevacizumab. The efficacy and safety of trabectedin and bevacizumab ± carboplatin have never been investigated.

Methods

In this phase 2 study, women progressing between 6 and 12 months since their last platinum-based therapy were randomised to Arm BT: bevacizumab, trabectedin every 21 days, or Arm BT+C: bevacizumab, trabectedin and carboplatin every 28 days, from cycles 1 to 6, then trabectedin and bevacizumab as in Arm BT. Primary endpoints were progression-free survival rate (PFS-6) and severe toxicity rate (ST-6) at 6 months, assuming a PFS-6 ≤35% for BT and ≤40% for BT+C as not of therapeutic interest and, for both arms, a ST-6  ≥ 30% as unacceptable.

Results

BT+C (21 patients) did not meet the safety criteria for the second stage (ST-6 45%; 95%CI: 23%–69%) but PFS-6 was 85% (95%CI: 62%–97%). BT (50 patients) had 75% PFS-6 (95%CI: 60%–87%) and 16% ST-6 (95%CI 7%–30%).

Conclusions

BT compared favourably with other platinum- and non-platinum-based regimens. The combination with carboplatin needs to be assessed further in a re-modulated safer schedule to confirm its apparent strong activity.

Clinical Trial Registration

NCT01735071 (Clinicaltrials.gov).

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Acknowledgements

The authors commemorate their colleague Irene Floriani of the Mario Negri Institute IRCCS, who passed away on 12 January 2016 and who dedicated her life to research. She was involved in the statistical design and coordination of this clinical trial. Writing assistance: Judith Baggott

Author information

Study concepts: N.C., M.D. Study design: V.T., E.R. Quality control of data and algorithms: E.N., A.P.G., D.P., C.G. Data analysis and interpretation: F.G., E.R., R.F. Statistical analysis: F.G. and E.R. Manuscript preparation: N.C., R.F. and FG Manuscript editing: N.C., E.N. and E.B. Manuscript review: all authors.

Correspondence to Roldano Fossati.

Ethics declarations

Competing interests

Nicoletta Colombo: Honoraria from Pharma Mar, Roche and other companies. Maurizio D’Incalci: Honoraria from Pharma Mar, Roche and other companies, Editorial Board Member of the British Journal of Cancer. The remaining authors declare no competing interests.

Ethics approval and consent to participate

Approved by the Coordinating Ethics Committee of the European Institute of Oncology, Milan (comitato.etico@ieo.it) on the 11 November 2012 (representative Dr Atanasio Nonis). The study was conducted in accordance with the International Conference on Harmonisation/Good Clinical Practice [ICH/GCP] and patients had to have signed written informed consent before randomisation.

Funding

Partial unconditional funding from Roche and Pharma Mar. Other funding from Mario Negri Institute IRCCS.

Consent to publish

The manuscript does not contain any individual person’s data in any form (individual details, images or videos).

Data availability

Data supporting the results reported can be found at Mario Negri Institute IRCCS for Pharmacologic Research, Milan. Data sharing is encouraged, and data are available on request to the corresponding author.

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