Phase II Study of NGR-hTNF Versus Placebo as Maintenance Treatment in Patients With Advanced MPM
- Conditions
- Advanced Malignant Pleural Mesothelioma
- Interventions
- Registration Number
- NCT01358084
- Lead Sponsor
- AGC Biologics S.p.A.
- Brief Summary
The main objective of the trial is to document the efficacy of NGR-hTNF administered as maintenance treatment at 0.8 µg/m2 weekly in advanced malignant pleural mesothelioma
- Detailed Description
First-line treatment of advanced malignant pleural mesothelioma (MPM) is based on six cycles of a pemetrexed-based chemotherapy, with a median progression-free survival (PFS) of approximately 6 months.However, the median time from completion of first-line treatment to initiation of second-line therapy is approximately 3 months. Recent experiences in non-small cell lung cancer patients have shown that a maintenance treatment given immediately after first-line treatment regimens can improve PFS and survival. Considering the toxicity profile of NGR-hTNF characterized by mild-to-moderate constitutional symptoms registered in a phase II trial in previously treated MPM patients, as well as the disease control observed in about half of the patients and maintained for more than four months and more than nine months in the triweekly and weekly cohorts, respectively, seems justified to compare in a randomized phase II trial the time-related efficacy of NGR-hTNF against placebo in advanced MPM patients who did not progress after six cycles of a standard pemetrexed-based treatment.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 137
-
Age ≥ 18 years
-
Histologically or cytological confirmed malignant pleural mesothelioma of any of the following subtype: epithelial, sarcomatoid, mixed, or unknown
-
Patients with non-progressive disease after six cycles of first-line, pemetrexed-based regimen administered for advanced or metastatic disease
-
ECOG Performance Status 0 - 1
-
Life expectancy of ≥ 12 weeks
-
Adequate baseline bone marrow, hepatic and renal function, defined as follows:
- Neutrophils ≥ 1.5 x 109/L; platelets ≥ 100 x109/L; hemoglobin ≥ 9 g/dL
- Bilirubin ≤ 1.5 x ULN
- AST and/or ALT ≤ 2.5 x ULN in absence of liver metastasis or ≤ 5 x ULN in presence of liver metastasis
- Serum creatinine < 1.5 x ULN
-
Measurable or non-measurable disease according to malignant pleural mesothelioma-modified RECIST criteria
-
Patients may have had prior therapy providing the following conditions are met:
- Surgery: wash-out period of 14 days
- Radiation therapy: wash-out period of 28 days
- Chemotherapy: wash-out period of 21 days
-
Patients must give written informed consent to participate in the study
- Patients must not receive any other investigational agents while on study
- Patients with myocardial infarction within the last six months, unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, or serious cardiac arrhythmia requiring medication
- Uncontrolled hypertension
- QTc interval (congenital or acquired) > 450 ms
- History or evidence upon physical examination of Central Nervous System disease unless adequately treated
- Patients with active or uncontrolled systemic disease/infections or with serious illness or medical conditions, which is incompatible with the protocol
- Known hypersensitivity/allergic reaction to human albumin preparations or to any of the excipients
- Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol
- Pregnancy or lactation.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm B: Placebo + Best Supportive Care Placebo Placebo + Best Supportive Care Arm A: NGR-hTNF + Best Supportive Care Best Supportive Care NGR-hTNF + Best Supportive Care Arm B: Placebo + Best Supportive Care Best Supportive Care Placebo + Best Supportive Care Arm A: NGR-hTNF + Best Supportive Care NGR-hTNF NGR-hTNF + Best Supportive Care
- Primary Outcome Measures
Name Time Method Progression-Free Survival (PFS) every 6 weeks Defined as the time from the date of randomization until disease progression, or death
- Secondary Outcome Measures
Name Time Method Overall survival (OS) every 6-12 weeks Defined as the time from the date of randomization until the date of death due to any cause or the last date the patient was known to be alive
Tumor response every 6 weeks Assessed according to modified RECIST criteria for MPM
Safety and Toxicity according to NCI-CTCAE criteria(version 4.03) during the study To evaluate safety and toxicity profile related to NGR-hTNF
Quality of life assessment by using a questionnaire according to Lung Cancer Symptom Scale (LCSS) From date of randomization until the end of treatment, assessed every 6 weeks To assess changes in quality of life (QoL) in the two treatment arms.
Trial Locations
- Locations (15)
Ospedale Santo Spirito
🇮🇹Casale Monferrato, Alessandria, Italy
Asklepios Fachkliniken München-Gauting
🇩🇪München-Gauting, Germany
Istituto Clinico Humanitas
🇮🇹Rozzano, Milan, Italy
Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo di Alessandria
🇮🇹Alessandria, Italy
IRCCS Ospedale San Raffaele
🇮🇹Milano, Italy
IRCCS Azienda Ospedaliera Universitaria San Martino IST Istituto Nazionale per la Ricerca sul Cancro
🇮🇹Genoa, Italy
Asl 3 genovese, Ospedale Villa Scassi
🇮🇹Genova, Italy
Istituto Oncologico Veneto
🇮🇹Padova, Italy
Azienda Ospedaliero-Universitaria di Parma
🇮🇹Parma, Italy
IRCCS Policlinico S. Matteo
🇮🇹Pavia, Italy
Azienda Unità Sanitaria locale di Ravenna
🇮🇹Ravenna, Italy
Ospedale Ca' Foncello
🇮🇹Treviso, Italy
Zentralklinik Bad Berka GmbH
🇩🇪Bad Berka, Thuringia, Germany
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori-IRST
🇮🇹Meldola, Forlì-Cesena, Italy
Saint Petersburg State Medical University n.a. I. P. Pavlov
🇷🇺Saint-Petersburg, Russian Federation