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

NCT02903004 | Completed Phase 3

• 1 other identifier: 986
• Study Type: interventional
• Target: 242
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

Ovarian Neoplasms

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS)

  The primary objective is to compare the Trabectedin versus physician' choice chemotherapy in terms of overall survival (OS).

  4 years

Secondary Outcomes (3)

• Progression free survival (PFS)

  4 years

• Duration of Response

  4 years

• Adverse events

  4 years

Study Arms (2)

Trabectedin

EXPERIMENTAL

Trabectedin 1.3 mg/m2 d1 q 21 in 3 hours (central line)

Drug: Trabectedin

Standard Treatment

OTHER

Pegylated Liposomal Doxorubicin 40 mg/mq q 28 or Topotecan 4 mg/ m2 dd 1,8,15 q 28 or Gemcitabine 1000 mg/mq dd 1, 8, 15 q 28 Weekly Paclitaxel 80 mg/ m2 dd 1, 8, 15 q 28 Carboplatin AUC 5-6 q 21 or 28

Drug: Pegylated Liposomal Doxorubicin; Drug: Topotecan; Drug: Gemcitabine; Drug: Weekly Paclitaxel; Drug: Carboplatin

Interventions

Trabectedin DRUG

Also known as: Yondelis

Trabectedin

Pegylated Liposomal Doxorubicin DRUG

Standard Treatment

Topotecan DRUG

Standard Treatment

Gemcitabine DRUG

Standard Treatment

Weekly Paclitaxel DRUG

Standard Treatment

Carboplatin DRUG

Standard Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female of age 18 years or older
• Histologically or cytologically documented invasive epithelial ovarian cancer, primary peritoneal carcinoma, or fallopian tube cancer
• Platinum resistant or sensitive patients with either:
• BRCA mutated patients
• BRCAness phenotype patients: patients who have received and responded (subsequent PFI\>6 months) to at least 2 previous platinum based chemotherapy lines
• Platinum sensitive patients who are not able to receive or not willing to receive other platinum treatments
• Measurable and evaluable disease per RECIST 1.1(Subjects with isolated rising CA-125 without radiologically visible disease are excluded)
• ECOG performance status 0 or 1
• No limits in the number of previous chemotherapy lines, previous treatment with parp inhibitors is allowed
• Left Ventricular Ejection Fraction (LVEF) ≥ institutional lower limit normal
• Life expectancy of at least 3 months
• Adequate organ functions:
• Hematopoietic: Absolute neutrophil count ≥ 1,500/mm3; Platelet count ≥ 100,000/mm3; Hemoglobin ≥ 9 g/dl
• Hepatic: AST and ALT ≤ 1.5 times upper limit of normal (ULN)\* ; Alkaline Phosphatase ≤ 2.5 times ULN\* ; Bilirubin ≤ 1.5 times ULN. NOTE: \* ≤ 3 times ULN if liver metastases are present
• Renal: Creatinine Clearance ≥ 45 ml/min or Serum Creatinine ≤1.5 x ULN

You may not qualify if:

• Prior exposure to trabectedin
• Known hypersensitivity to any of the components of the trabectedin i.v. formulation or dexamethasone
• Subjects with borderline ovarian cancer, ie. Subject with low malignant potential tumors are excluded
• Less than 2 reported responses to platinum (i.e. subsequent recurrences at least 6 months after the first and the second platinum based treatment), unless BRCA mutation is documented.
• Less than 4 weeks from last dose of therapy with any investigational agent, or chemotherapy
• History of another neoplastic disease (except basal cell carcinoma or cervical carcinoma in situ adequately treated) unless in remission for 3 years or longer
• Known clinically relevant CNS metastases, unless treated and asymptomatic
• Other serious illnesses, such as:
• Congestive heart failure or angina pectoris; myocardial infarction within 1 year before enrolment; uncontrolled arterial hypertension or arrhythmias.
• Psychiatric disorder that prevents compliance with protocol.
• Active viral hepatitis; or chronic liver disease.
• Active infection.
• Any other unstable medical conditions.

Sponsors & Collaborators

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS: lead

Study Sites (1)

Domenica Lorusso

Rome, 00168, Italy

Location

Related Publications (13)

• 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)

  BACKGROUND

• 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.

  PMID: 11479630 RESULT

• 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.

  PMID: 11304695 RESULT

• 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.

  PMID: 21376569 RESULT

• 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.

  PMID: 23410977 RESULT

• 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.

  PMID: 23397080 RESULT

• 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.

  PMID: 11165136 RESULT

• 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.

  PMID: 16912194 RESULT

• 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.

  PMID: 21835933 RESULT

• 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.

  PMID: 10655437 RESULT

• 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.

  PMID: 38315944 DERIVED

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

Trabectedin; liposomal doxorubicin; Topotecan; Gemcitabine; Carboplatin

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Dioxoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrahydroisoquinolines; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Camptothecin; Alkaloids; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Coordination Complexes; Organic Chemicals

Study Officials

• Domenica Lorusso, Prof.

  Fondazione Policlinico Universitario A. Gemelli, IRCCS

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 26, 2016
• First Posted: September 16, 2016
• Study Start: April 11, 2016
• Primary Completion: December 20, 2018
• Study Completion: December 20, 2018
• Last Updated: August 25, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)