ATREUS - Phase II Study on the Activity of Trabectedin in Patients With Malignant Pleural Mesothelioma (MPM)

NCT02194231 | Completed Phase 2

• 2 other identifiers: IRFMN-MPM-60772011-006330-16
• Study Type: interventional
• Target: 145
• Locations: 1 country
• Sites: 8

Brief Summary

The purpose of this study is to determine whether trabectedin is effective in the treatment of malignant pleural mesothelioma (MPM).

Conditions

Malignant Pleural Mesothelioma

Keywords

Mesothelioma; MPM; Trabectedin

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival - PFS12w

  Proportion of patients free from progression or death at the second CT scan assessment performed at 12 weeks (Progression Free Survival - PFS12w) from the date of treatment start

  12 weeks

Secondary Outcomes (10)

• Progression Free Survival (PFS)

  24 months

• Overall survival (OS)

  24 months

• Objective response rate

  24 months

• Trabectedin tolerability and safety

  24 months

• Pain Intensity (PI)

  24 months

Study Arms (1)

Trabectedin

EXPERIMENTAL

Patients will receive trabectedin treatment

Drug: Trabectedin

Interventions

Trabectedin DRUG

Patients will receive 1.1 mg/m2 intravenous trabectedin infusion in 5% glucose via central venous catheter over 3 hours every 21 days. Trabectedin infusion will be preceded by 20 mg of intravenous dexamethasone

Also known as: Yondelis

Trabectedin

Eligibility Criteria

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

You may qualify if:

• Histologically proven unresectable MPM. In order to make a reproducible diagnosis, in particular regarding biphasic MPM, histology must derive from transthoracic biopsies (at least 3 representative samples) or from videothoracoscopy (at least 5 representative samples)
• Age \>18 years
• Performance status 0-1 (ECOG)
• Measurable disease (CT-PET) according to RECIST criteria modified for malignant pleural mesothelioma
• Not more than one previous chemotherapy course (consisting of pemetrexed plus platinum derivative), excluded adjuvant therapy if PFS \< 12 months
• A minimum of 3 weeks since previous tumour directed therapy
• Recovery from toxic effects of previous therapies to NCI CTC AE Grade 0-1
• Patients who have received palliative radiation are eligible if \<30% of bone marrow was irradiated and normal haematological function was completely regained
• Haematologic variables: haemoglobin ≥ 9 g/dL, Absolute neutrophil count (ANC) ≥ 1,500/μL and Platelet count ≥ 100,000/μL
• Serum creatinine ≤1.5 mg/dL or creatinine clearance ≥ 30 mL/min
• Creatinine phosphokinase (CPK) ≤ 2.5 ULN
• Hepatic function variables: Total bilirubin ≤ ULN, Total alkaline phosphatase ≤ 2.5 ULN or if \> 2.5 ULN alkaline phosphatase liver fraction or GGT or 5' nucleotidase must be determined and ≤ ULN, AST (serum aspartate transaminase \[SGOT\]) and ALT (serum alaninetransaminase \[SGPT\]) must be ≤ 2.5 x ULN, Albumin ≥ 25 g/L
• Signed informed consent
• Adequate contraceptive methods for male patients whose partner is of childbearing age/potential, during the study and for three months after the end of treatment

You may not qualify if:

• \- Radiotherapy with curative intent to thoracic wall (concomitant with or prior to chemotherapy)
• \- Uncompensated diabetes mellitus or other condition absolutely contra-indicating dexamethasone (used as pre-medication)
• \- Patients enrolled in other study with experimental drugs
• \- Women of childbearing age/potential
• \- Prior exposure to trabectedin
• \- History of other malignancies (except basal cell carcinoma or cervical carcinoma in situ, adequately treated), unless in remission from 5 years or more and judged of negligible potential of relapse
• \- Active viral hepatitis or chronic liver disease
• \- Unstable cardiac condition, including congestive heart failure or angina pectoris, myocardial infarction within one year before enrolment, uncontrolled arterial hypertension or arrhythmias
• \- Active major infection
• \- Other serious concomitant illness
• \- Brain / leptomeningeal involvement

Sponsors & Collaborators

• Mario Negri Institute for Pharmacological Research: lead
• PharmaMar: collaborator

Study Sites (8)

Azienda ospedaliera ss. Antonio e Biagio e Cesare Arrigo

Alessandria, AL, Italy

Location

Cliniche Humanitas Gavazzeni

Bergamo, BG, Italy

Location

Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi

Bologna, Bo, 40138, Italy

Location

P.O. Spedalli Civili

Brescia, BS, 25125, Italy

Location

Azienda Ospedaliera S. Gerardo di Monza

Monza, MB, 20900, Italy

Location

Istituto Clinico Humanitas

Rozzano, MI, 20089, Italy

Location

Istituto Oncologico Veneto - IOV

Padua, PD, 35128, Italy

Location

Azienda Ospedaliro-Universitaria di Parma

Parma, 43126, Italy

Location

Related Publications (6)

• Pommier Y, Kohlhagen G, Bailly C, Waring M, Mazumder A, Kohn KW. DNA sequence- and structure-selective alkylation of guanine N2 in the DNA minor groove by ecteinascidin 743, a potent antitumor compound from the Caribbean tunicate Ecteinascidia turbinata. Biochemistry. 1996 Oct 15;35(41):13303-9. doi: 10.1021/bi960306b.

  PMID: 8873596 RESULT

• Bonfanti M, La Valle E, Fernandez Sousa Faro JM, Faircloth G, Caretti G, Mantovani R, D'Incalci M. Effect of ecteinascidin-743 on the interaction between DNA binding proteins and DNA. Anticancer Drug Des. 1999 Jun;14(3):179-86.

  PMID: 10500494 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

• Demetri GD, Chawla SP, von Mehren M, Ritch P, Baker LH, Blay JY, Hande KR, Keohan ML, Samuels BL, Schuetze S, Lebedinsky C, Elsayed YA, Izquierdo MA, Gomez J, Park YC, Le Cesne A. Efficacy and safety of trabectedin in patients with advanced or metastatic liposarcoma or leiomyosarcoma after failure of prior anthracyclines and ifosfamide: results of a randomized phase II study of two different schedules. J Clin Oncol. 2009 Sep 1;27(25):4188-96. doi: 10.1200/JCO.2008.21.0088. Epub 2009 Aug 3.

  PMID: 19652065 RESULT

• Del Campo JM, Roszak A, Bidzinski M, Ciuleanu TE, Hogberg T, Wojtukiewicz MZ, Poveda A, Boman K, Westermann AM, Lebedinsky C; Yondelis Ovarian Cancer Group. Phase II randomized study of trabectedin given as two different every 3 weeks dose schedules (1.5 mg/m2 24 h or 1.3 mg/m2 3 h) to patients with relapsed, platinum-sensitive, advanced ovarian cancer. Ann Oncol. 2009 Nov;20(11):1794-802. doi: 10.1093/annonc/mdp198. Epub 2009 Jun 25.

  PMID: 19556318 RESULT

• D'Incalci M, Galmarini CM. A review of trabectedin (ET-743): a unique mechanism of action. Mol Cancer Ther. 2010 Aug;9(8):2157-63. doi: 10.1158/1535-7163.MCT-10-0263. Epub 2010 Jul 20.

  PMID: 20647340 RESULT

MeSH Terms

Conditions

Mesothelioma, Malignant; Mesothelioma

Interventions

Trabectedin

Condition Hierarchy (Ancestors)

Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Pleural Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Dioxoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrahydroisoquinolines; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Paolo Bidoli, MD

  Azienda Ospedaliera San Gerardo di Monza

  PRINCIPAL INVESTIGATOR

• Valter Torri, MD

  Istituto Di Ricerche Farmacologiche Mario Negri

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 16, 2014
• First Posted: July 18, 2014
• Study Start: July 1, 2013
• Primary Completion: December 12, 2019
• Study Completion: December 12, 2019
• Last Updated: January 23, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will share

Locations

IT (8)