Trial on Trabectedin (ET-743) vs Clinician's Choice Chemotherapy in Recurrent Ovarian, Primary Peritoneal or Fallopian Tube Cancers of BRCA Mutated or BRCAness Phenotype Patients

Summary

This is an open-label, prospective, multicenter, randomized Phase III, clinical trial evaluating the efficacy and safety of trabectedin in BRCA1 and BRCA2 mutation carrier and BRCAness phenotype advanced ovarian cancer patients in comparison to physician' choice chemotherapy. Arm A: Trabectedin 1.3 mg/mq d1 q 21 in 3 hours (central line) Arm B: Pegylated Liposomal Doxorubicin 40 mg/mq q 28 or Topotecan 4 mg/mq dd 1,8,15 q 28 or Gemcitabine 1000 mg/mq dd 1, 8, 15 q 28 Weekly Paclitaxel 80 mg/mq gg 1, 8, 15 q 28 Carboplatin AUC 5-6 q 21 or 28 Patients will be randomly assigned in a 1:1 ratio to treatment arms. During the randomization process, patients will be stratified by * Platinum sensitivity * Measurable disease * Number of previous chemotherapy lines \> vs \< 3 * BRCA mutational status

Timeline

Start

2016-04-11

Primary completion

2018-12-20

Completion

2018-12-20

Publications

• Background Salutari V, Ferrandina G, Vincenzi B et al. Efficacy and safety outcomes in heavily pretreated patients (pts) with relapsed ovarian cancer (roc ) after single agent trabectedin. ASCO 2013, submitted.
• Background Monk BJ, Herzog T, Kay S et al. A randomized Phase III study of trabectedin with pegylated liposomal doxorubicin (PLD) versus PLD in relapsed, recurrent ovarian cancer (OC). Ann. Oncol. 19(Suppl. 8), (2009)
• Background K. L. Tedesco, J. L. Blum, A. Goncalves, J. Lubinski, N. Ben-Baruch, C. R. Osborne, P. Lardelli, A et al. phase II trial of trabectedin (T) in patients (pts) with HER2-positive and BRCA1/2 germ-line-mutated metastatic breast cancer (MBC). J Clin Oncol 28:15s, 2010 (suppl; abstr 1038)
• Results Takebayashi Y, Pourquier P, Zimonjic DB, Nakayama K, Emmert S, Ueda T, Urasaki Y, Kanzaki A, Akiyama SI, Popescu N, Kraemer KH, Pommier Y. Antiproliferative activity of ecteinascidin 743 is dependent upon transcription-coupled nucleotide-excision repair. Nat Med. 2001 Aug;7(8):961-6. doi: 10.1038/91008.
• Results Damia G, Silvestri S, Carrassa L, Filiberti L, Faircloth GT, Liberi G, Foiani M, D'Incalci M. Unique pattern of ET-743 activity in different cellular systems with defined deficiencies in DNA-repair pathways. Int J Cancer. 2001 May 15;92(4):583-8. doi: 10.1002/ijc.1221.
• Results Schoffski P, Taron M, Jimeno J, Grosso F, Sanfilipio R, Casali PG, Le Cesne A, Jones RL, Blay JY, Poveda A, Maki RG, Nieto A, Tercero JC, Rosell R. Predictive impact of DNA repair functionality on clinical outcome of advanced sarcoma patients treated with trabectedin: a retrospective multicentric study. Eur J Cancer. 2011 May;47(7):1006-12. doi: 10.1016/j.ejca.2011.01.016. Epub 2011 Mar 4.
• Results Germano G, Frapolli R, Belgiovine C, Anselmo A, Pesce S, Liguori M, Erba E, Uboldi S, Zucchetti M, Pasqualini F, Nebuloni M, van Rooijen N, Mortarini R, Beltrame L, Marchini S, Fuso Nerini I, Sanfilippo R, Casali PG, Pilotti S, Galmarini CM, Anichini A, Mantovani A, D'Incalci M, Allavena P. Role of macrophage targeting in the antitumor activity of trabectedin. Cancer Cell. 2013 Feb 11;23(2):249-62. doi: 10.1016/j.ccr.2013.01.008.
• Results del Campo JM, Sessa C, Krasner CN, Vermorken JB, Colombo N, Kaye S, Gore M, Zintl P, Gomez J, Parekh T, Park YC, McMeekin S. Trabectedin as single agent in relapsed advanced ovarian cancer: results from a retrospective pooled analysis of three phase II trials. Med Oncol. 2013 Mar;30(1):435. doi: 10.1007/s12032-012-0435-1. Epub 2013 Feb 9.
• Results Erba E, Bergamaschi D, Bassano L, Damia G, Ronzoni S, Faircloth GT, D'Incalci M. Ecteinascidin-743 (ET-743), a natural marine compound, with a unique mechanism of action. Eur J Cancer. 2001 Jan;37(1):97-105. doi: 10.1016/s0959-8049(00)00357-9.
• Results Herrero AB, Martin-Castellanos C, Marco E, Gago F, Moreno S. Cross-talk between nucleotide excision and homologous recombination DNA repair pathways in the mechanism of action of antitumor trabectedin. Cancer Res. 2006 Aug 15;66(16):8155-62. doi: 10.1158/0008-5472.CAN-06-0179.
• Results Safra T, Borgato L, Nicoletto MO, Rolnitzky L, Pelles-Avraham S, Geva R, Donach ME, Curtin J, Novetsky A, Grenader T, Lai WC, Gabizon A, Boyd L, Muggia F. BRCA mutation status and determinant of outcome in women with recurrent epithelial ovarian cancer treated with pegylated liposomal doxorubicin. Mol Cancer Ther. 2011 Oct;10(10):2000-7. doi: 10.1158/1535-7163.MCT-11-0272. Epub 2011 Aug 11.
• Results Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000 Feb 2;92(3):205-16. doi: 10.1093/jnci/92.3.205.
• Lorusso D, Raspagliesi F, Ronzulli D, Valabrega G, Colombo N, Pisano C, Cassani C, Tognon G, Tamberi S, Mangili G, Mammoliti S, De Giorgi U, Greco F, Mosconi AM, Breda E, Artioli G, Andreetta C, Casanova C, Ceccherini R, Frassoldati A, Salutari V, Giolitto S, Scambia G. Single-Agent Trabectedin Versus Physician's Choice Chemotherapy in Patients With Recurrent Ovarian Cancer With BRCA-Mutated and/or BRCAness Phenotype: A Randomized Phase III Trial. J Clin Oncol. 2024 May 1;42(13):1488-1498. doi: 10.1200/JCO.23.01225. Epub 2024 Feb 5.

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