ATREUS - Phase II Study on the Activity of Trabectedin in Patients With Malignant Pleural Mesothelioma (MPM) (ATREUS)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02194231|
Recruitment Status : Recruiting
First Posted : July 18, 2014
Last Update Posted : August 4, 2017
|Condition or disease||Intervention/treatment||Phase|
|Malignant Pleural Mesothelioma||Drug: Trabectedin||Phase 2|
There are no approved agents for second-line treatment of MPM in patients who failed first line pemetrexed plus platinum derivatives regimens. Chemotherapy options are limited and include gemcitabine, vinorelbine and other antifolate compounds. The role of second-line chemotherapy is therefore not yet established and second-line patient population is considered suitable for phase II studies with investigational agents.
Trabectedin is an originally natural marine product, now obtained by a semisynthetic process, that induces a delay in S phase progression and a blockade in G2 phase of the cell cycle by a mode of action that seems different from that of other DNA-damaging agents (see citations). Although the exact mechanism of action of trabectedin has not been fully elucidated yet, it appears to be unique compared to other anticancer agents (see citations). Trabectedin binds to N2 of guanines in the minor groove of DNA, causing a bending of the minor groove towards the major groove.
In the randomised clinical trials in metastatic leiomyosarcoma or liposarcoma and in recurrent platinum-sensitive ovarian cancer, trabectedin is infused at 1.5 mg/m2 as a 24-hour infusion or 1.3 mg/m2 as a 3 hour infusion every 3 weeks (see citations). Balancing efficacy with safety the short infusion is preferable in clinical practice.
In soft tissue sarcoma the response rate did not exceed 10%, however, trabectedin has been shown to provide disease control, with progression arrest rates exceeding 50% and progression-free survival rates exceeding 20% at 6 months. In pre-treated ovarian cancer the objective response rate was 30% with a median time to disease progression of 5.7 months.
Trabectedin has not been extensively employed in MPM, however in phase I studies, some objective response in heavily pre-treated mesothelioma patients was seen.
The present study is aimed at evaluating the activity of trabectedin in MPM patients not candidate for radical surgery. This option is of particular interest due to lack of valid therapeutic options.
Translational studies will be performed to identify factors predictive of the activity of trabectedin in MPM.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||141 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||ATREUS Trial - A Phase II Study on the Activity of Trabectedin of Pretreated Epithelioid or Biphasic / Sarcomatoid Malignant Pleural Mesothelioma(MPM)|
|Study Start Date :||July 2013|
|Estimated Primary Completion Date :||November 2017|
|Estimated Study Completion Date :||November 2017|
Patients will receive trabectedin treatment
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
Other Name: Yondelis
- Progression Free Survival - PFS12w [ Time Frame: 12 weeks ]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
- Progression Free Survival (PFS) [ Time Frame: 24 months ]PFS will be evaluated by CT scans every 6 weeks from the date of first treatment until week 12 and subsequently every 8-9 weeks
- Overall survival (OS) [ Time Frame: 24 months ]
- Objective response rate [ Time Frame: 24 months ]Responses will be assessed according to Modified RECIST criteria for Malignant Pleural Mesothelioma
- Trabectedin tolerability and safety [ Time Frame: 24 months ]Safety will be evaluated based on reported AEs, clinical laboratory assessments, vital signs and physical examinations. Adverse events will be encoded using the Medical Dictionary for Regulatory Activities (MedDRA) and graded using NCI-CTCAE ver 4
- Pain Intensity (PI) [ Time Frame: 24 months ]Pain intensity will be evaluated by using an 11 points Numerical Rating Scale (NRS), where 0 indicates no pain and 10 indicates the worst pain one can imagine. Patients will be requested to evaluate the PI related to the 24 hours preceding the visit and indicating the score for the average, worst and least PI
- Pain type and characteristics [ Time Frame: 24 months ]With special reference to the presence of neuropathic pain, evaluation shall be carried out using the DN4 questionnaire. The global score on this 10 item instrument allows to diagnose the presence of neuropathic pain (total score ≥4)
- Antalgic treatments [ Time Frame: 24 months ]Evaluation of type and dosage of any pain medication administered to the patient at the moment of the study visit
- microRNA (miRs) profile [ Time Frame: 24 months ]
miRs profile evaluation will be performed with the aim of characterising the tumour biological features associated to the different response patterns. Since recent published studies suggests that trabectedin modulates the expression of some miRs in cancer cells exposed to the drug and, also, the resistance to anticancer drugs seems to be well correlated to the expression of some specific miRs, the evaluation of miRs expression may become a powerful prognostic and predictive marker.
miRNA landscape in both plasma and tumour tissues will be profiled using commercially available oligo arrays platforms.
- High Mobility Group B1 (HMGB1) protein assessment [ Time Frame: 24 months ]
Recent data indicate that the high mobility group B1 (HMGB1) is implicated in the transformation of meshothelial cells and is strongly secreted in sera of patients with mesothelioma. These findings provide the rationale for considering HMGB1 as a potential useful marker to monitor therapeutic effectiveness in patients with mesothelioma.
HMGB1 will be determined in plasma of patients at the same time points previously indicated for the assessment of miR profiles by using an ELISA essay
- Blood Macrophages analysis [ Time Frame: 24 months ]
We propose to analyse the effects of trabectedin on the number of circulating monocytes and the plasma levels of selected biological mediators. A decrease in the number of circulating monocytes could be a surrogate marker of a biological effect of trabectedin on the precursor cells of tumour macrophages.
We propose to collect the number of circulating monocytes during the first 3 treatment cycles, immediately before and 7 days after trabectedin administration
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02194231
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02194231
|Contact: Luciano Carlucci, PhD||0039023901 ext firstname.lastname@example.org|
|Azienda ospedaliera ss. Antonio e Biagio e Cesare Arrigo||Recruiting|
|Alessandria, AL, Italy|
|Contact: Federica Grosso, MD email@example.com|
|Contact: Annalisa Roveta 00390131206976 firstname.lastname@example.org|
|Principal Investigator: Federica Grosso, MD|
|Cliniche Humanitas Gavazzeni||Recruiting|
|Bergamo, BG, Italy|
|Contact: Giovanni L Ceresoli, MD email@example.com|
|Contact: Paola Maggioni 00390354204760 firstname.lastname@example.org|
|Principal Investigator: Giovanni L Ceresoli, MD|
|Principal Investigator: Maria G Sauta, MD|
|Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi||Not yet recruiting|
|Bologna, Bo, Italy, 40138|
|Contact: Andrea Ardizzoni, MD email@example.com|
|Principal Investigator: Andrea Ardizzoni, MD|
|P.O. Spedalli Civili||Not yet recruiting|
|Brescia, BS, Italy, 25125|
|Contact: Gianfranco MD Tassi|
|Principal Investigator: Alberto Caprioli, MD|
|ASL 3 Genovese - Ospedale Villa Scassi||Not yet recruiting|
|Genova, GE, Italy, 16149|
|Contact: Manlio Mencoboni, MD firstname.lastname@example.org|
|Principal Investigator: Manlio Mencoboni, MD|
|Azienda Ospedaliera S. Gerardo di Monza||Recruiting|
|Monza, MB, Italy, 20900|
|Contact: Monica Perez Gila 00390392333203 email@example.com|
|Principal Investigator: Paolo Bidoli, MD|
|Sub-Investigator: Diego Cortinovis, MD|
|Sub-Investigator: Stefania Canova, MD|
|Istituto Clinico Humanitas||Recruiting|
|Rozzano, MI, Italy, 20089|
|Contact: Paolo Zucali, MD 00390282244061 firstname.lastname@example.org|
|Contact: Monica Bertossi 00390282244032 email@example.com|
|Principal Investigator: Armando Santoro, MD|
|Sub-Investigator: Paolo Zucali, MD|
|Istituto Oncologico Veneto - IOV||Recruiting|
|Padova, PD, Italy, 35128|
|Contact: Giulia Pasello, MD firstname.lastname@example.org|
|Principal Investigator: Giulia Pasello, MD|
|Azienda Ospedaliro-Universitaria di Parma||Recruiting|
|Parma, Italy, 43126|
|Contact: Marcello Tiseo, MD 00390521702682 email@example.com|
|Contact: Elena Rapacchi 00390521702682 firstname.lastname@example.org|
|Principal Investigator: Marcello Tiseo, MD|
|Sub-Investigator: Sebastiano Buti, MD|
|Sub-Investigator: Francesco Facchinetti, MD|
|Principal Investigator:||Paolo Bidoli, MD||Azienda Ospedaliera San Gerardo di Monza|
|Study Chair:||Valter Torri, MD||Istituto Di Ricerche Farmacologiche Mario Negri|