Trial On Trabectedin In The Treatment Of Advanced Uterine And Ovarian Carcinosarcoma (CS)

Carcinosarcoma, Ovarian Clinical Trial

— MITO 26  

Official title:

Phase II Trial On Trabectedin In The Treatment Of Advanced Uterine And Ovarian Carcinosarcoma (CS)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02993705
• Other study ID #: 1561
• Status: Completed
• Phase: Phase 2
• Start date: February 22, 2017
• Est. completion date: November 13, 2019

Study information

• Verified date: August 2021
• Source: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Multicenter phase II study on trabectedin in patients advanced uterine and ovarian carcinosarcoma. Patients will receive trabectedin until disease progression or unacceptable toxicity. Disease response evaluation will be assessed every 9 weeks.

Description:

This is a Phase II, multi-centre, single arm study aiming at evaluating efficacy and toxicity of Trabectedin in a population of advanced or recurrent ovarian and uterine carcinosarcoma.

Trabectedin will be infused at the dose of 1.3 mg/m2 as a 3- hour iv infusion every 3 weeks via a central venous catheter.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: November 13, 2019
• Est. primary completion date: November 13, 2019
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 100 Years

Eligibility

Inclusion Criteria:

• Histologically documented Stage I-IV or recurrent uterine or ovarian carcinosarcoma not amenable to surgery or radiotherapy

• No more than 2 previous chemotherapy lines

• PS 0-2 (ECOG)

• Age> 18

• Measurable disease

• Life expectancy of at least 3 months

• Adequate organ functions:

• Hematopoietic; Absolute neutrophil count = 1,500/mm^3; Platelet count = 100,000/mm^3; Hemoglobin = 9 g/dL Hepatic; AST and ALT = 1.5 times upper limit of normal (ULN)*; Protocol Version 1.0_05.09.2016 6 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 Serum Albumin >3.0 g/dL

• Previous Brachytherapy treatment for uterine carcinosarcoma is allowed

• No other invasive malignancy within the past 3 years except non-melanoma skin cancer

• Written Informed Consent

Exclusion Criteria:

• More than 2 previous chemotherapy lines

• Single tumor lesion inside a previous irradiated filed

• Pregnant (potentially fertile patients must be not in pregnancy during and for at least 3 months after study participation and must have a negative serum pregnancy test)

• Active infection requiring antibiotics

• Symptomatic peripheral neuropathy > grade 2 according to the NCI Common Toxicity Criteria.

• Congestive heart failure or angina pectoris even if it is medically controlled. Previous history of myocardial infarction within 1 year from study entry, uncontrolled high risk hypertension or arrhythmia.

• Unstable or severe intercurrent medical condition that, in the opinion of the investigator, might interfere with achievement of study objectives

• Psychological or sociological conditions, addictive disorders, or family problems, which would preclude compliance with the protocol

Related Conditions & MeSH terms

• Carcinosarcoma
• Carcinosarcoma, Ovarian
• Carcinosarcomas Uterine
• Mixed Tumor, Mullerian

Intervention

Drug:
• Trabectedin
Chemotherapy drug

Locations

Country	Name	City	State
Italy	Fondazione Policlinico Universitario Agostino Gemelli IRCCS	Rome

Sponsors (1)

Lead Sponsor	Collaborator
Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Country where clinical trial is conducted

Italy, 

References & Publications (17)

Berton-Rigaud D, Devouassoux-Shisheboran M, Ledermann JA, Leitao MM, Powell MA, Poveda A, Beale P, Glasspool RM, Creutzberg CL, Harter P, Kim JW, Reed NS, Ray-Coquard I. Gynecologic Cancer InterGroup (GCIG) consensus review for uterine and ovarian carcino — View Citation

Cicin I, Saip P, Eralp Y, Selam M, Topuz S, Ozluk Y, Aydin Y, Topuz E. Ovarian carcinosarcomas: clinicopathological prognostic factors and evaluation of chemotherapy regimens containing platinum. Gynecol Oncol. 2008 Jan;108(1):136-40. Epub 2007 Oct 23. — View Citation

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. — View Citation

del Campo JM, Sessa C, Krasner CN, Vermorken JB, Colombo N, Kaye S, Gore M, Zintl P, Gómez 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 tr — View Citation

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, M — View Citation

Homesley HD, Filiaci V, Markman M, Bitterman P, Eaton L, Kilgore LC, Monk BJ, Ueland FR; Gynecologic Oncology Group. Phase III trial of ifosfamide with or without paclitaxel in advanced uterine carcinosarcoma: a Gynecologic Oncology Group Study. J Clin On — View Citation

Jonson AL, Bliss RL, Truskinovsky A, Judson P, Argenta P, Carson L, Dusenbery K, Downs LS Jr. Clinical features and outcomes of uterine and ovarian carcinosarcoma. Gynecol Oncol. 2006 Mar;100(3):561-4. Epub 2005 Nov 4. — View Citation

Leiser AL, Chi DS, Ishill NM, Tew WP. Carcinosarcoma of the ovary treated with platinum and taxane: the memorial Sloan-Kettering Cancer Center experience. Gynecol Oncol. 2007 Jun;105(3):657-61. Epub 2007 Mar 28. — View Citation

Makker V, Abu-Rustum NR, Alektiar KM, Aghajanian CA, Zhou Q, Iasonos A, Hensley ML. A retrospective assessment of outcomes of chemotherapy-based versus radiation-only adjuvant treatment for completely resected stage I-IV uterine carcinosarcoma. Gynecol On — View Citation

Reed NS, Mangioni C, Malmström H, Scarfone G, Poveda A, Pecorelli S, Tateo S, Franchi M, Jobsen JJ, Coens C, Teodorovic I, Vergote I, Vermorken JB; European Organisation for Research and Treatment of Cancer Gynaecological Cancer Group. Phase III randomise — View Citation

Schoffski P, Casali PP, Taron M, et al. Impact of the DNA repair functionality on the outcome of sarcoma patients treated with trabectedin (ET-743). J Clin Oncol, 2006; 24 (18 Suppl):525s (Abstract#9522)

Sutton G, Brunetto VL, Kilgore L, Soper JT, McGehee R, Olt G, Lentz SS, Sorosky J, Hsiu JG. A phase III trial of ifosfamide with or without cisplatin in carcinosarcoma of the uterus: A Gynecologic Oncology Group Study. Gynecol Oncol. 2000 Nov;79(2):147-53 — View Citation

Sutton G, Kauderer J, Carson LF, Lentz SS, Whitney CW, Gallion H; Gynecologic Oncology Group. Adjuvant ifosfamide and cisplatin in patients with completely resected stage I or II carcinosarcomas (mixed mesodermal tumors) of the uterus: a Gynecologic Oncol — View Citation

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. — View Citation

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 Tr — View Citation

Toyoshima M, Akahira J, Matsunaga G, Niikura H, Ito K, Yaegashi N, Tase T. Clinical experience with combination paclitaxel and carboplatin therapy for advanced or recurrent carcinosarcoma of the uterus. Gynecol Oncol. 2004 Sep;94(3):774-8. — View Citation

Wolfson AH, Brady MF, Rocereto T, Mannel RS, Lee YC, Futoran RJ, Cohn DE, Ioffe OB. A gynecologic oncology group randomized phase III trial of whole abdominal irradiation (WAI) vs. cisplatin-ifosfamide and mesna (CIM) as post-surgical therapy in stage I-I — View Citation

* Note: There are 17 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective response rate (ORR)	The primary endpoint of this study is to evaluate the activity of trabectedin in terms of the objective response rate (ORR) in patients with advanced uterine and ovarian carcinosarcoma.	three years
Secondary	Duration of response		three years
Secondary	Progression Free Survival (PFS)	the diagnosis of progression will be assessed by radiological criteria; CA 125 increases alone (GCIG criteria of progression) will not be considered as progression of disease without a radiological confirmation of progression	three years
Secondary	Overall Survival (OS)		three years
Secondary	Adverse events	Incidence of adverse events, according to the National Cancer Institute Common Toxicity Criteria (NCI-CTC) v 4.03.	three years