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

Nicoletta Colombo, Eleonora Zaccarelli, Alessandra Baldoni, Simona Frezzini, Giovanni Scambia, Eleonora Palluzzi, Germana Tognon, Andrea A Lissoni, Daniela Rubino, Annamaria Ferrero, Gabriella Farina, Emanuele Negri, Angela Pesenti Gritti, Francesca Galli, Elena Biagioli, Eliana Rulli, Davide Poli, Chiara Gerardi, Valter Torri, Roldano FossatiMaurizio D'Incalci

Research output: Contribution to journalArticle

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).

Original languageEnglish
JournalBritish Journal of Cancer
DOIs
Publication statusE-pub ahead of print - Sep 20 2019

Fingerprint

trabectedin
Carboplatin
Platinum
Ovarian Neoplasms
Safety
Tumor Microenvironment
Disease-Free Survival
Appointments and Schedules
Survival Rate
Bevacizumab
Clinical Trials

Cite this

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. / Colombo, Nicoletta; Zaccarelli, Eleonora; Baldoni, Alessandra; Frezzini, Simona; Scambia, Giovanni; Palluzzi, Eleonora; Tognon, Germana; Lissoni, Andrea A; Rubino, Daniela; Ferrero, Annamaria; Farina, Gabriella; Negri, Emanuele; Pesenti Gritti, Angela; Galli, Francesca; Biagioli, Elena; Rulli, Eliana; Poli, Davide; Gerardi, Chiara; Torri, Valter; Fossati, Roldano; D'Incalci, Maurizio.

In: British Journal of Cancer, 20.09.2019.

Research output: Contribution to journalArticle

Colombo, Nicoletta ; Zaccarelli, Eleonora ; Baldoni, Alessandra ; Frezzini, Simona ; Scambia, Giovanni ; Palluzzi, Eleonora ; Tognon, Germana ; Lissoni, Andrea A ; Rubino, Daniela ; Ferrero, Annamaria ; Farina, Gabriella ; Negri, Emanuele ; Pesenti Gritti, Angela ; Galli, Francesca ; Biagioli, Elena ; Rulli, Eliana ; Poli, Davide ; Gerardi, Chiara ; Torri, Valter ; Fossati, Roldano ; D'Incalci, Maurizio. / 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. In: British Journal of Cancer. 2019.
@article{cbd353259b7b4edab75241249f8a7ec0,
title = "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",
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).",
author = "Nicoletta Colombo and Eleonora Zaccarelli and Alessandra Baldoni and Simona Frezzini and Giovanni Scambia and Eleonora Palluzzi and Germana Tognon and Lissoni, {Andrea A} and Daniela Rubino and Annamaria Ferrero and Gabriella Farina and Emanuele Negri and {Pesenti Gritti}, Angela and Francesca Galli and Elena Biagioli and Eliana Rulli and Davide Poli and Chiara Gerardi and Valter Torri and Roldano Fossati and Maurizio D'Incalci",
year = "2019",
month = "9",
day = "20",
doi = "10.1038/s41416-019-0584-5",
language = "English",
journal = "British Journal of Cancer",
issn = "0007-0920",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - 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

AU - Colombo, Nicoletta

AU - Zaccarelli, Eleonora

AU - Baldoni, Alessandra

AU - Frezzini, Simona

AU - Scambia, Giovanni

AU - Palluzzi, Eleonora

AU - Tognon, Germana

AU - Lissoni, Andrea A

AU - Rubino, Daniela

AU - Ferrero, Annamaria

AU - Farina, Gabriella

AU - Negri, Emanuele

AU - Pesenti Gritti, Angela

AU - Galli, Francesca

AU - Biagioli, Elena

AU - Rulli, Eliana

AU - Poli, Davide

AU - Gerardi, Chiara

AU - Torri, Valter

AU - Fossati, Roldano

AU - D'Incalci, Maurizio

PY - 2019/9/20

Y1 - 2019/9/20

N2 - 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).

AB - 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).

U2 - 10.1038/s41416-019-0584-5

DO - 10.1038/s41416-019-0584-5

M3 - Article

C2 - 31537908

JO - British Journal of Cancer

JF - British Journal of Cancer

SN - 0007-0920

ER -