Clinical trial NCT01358084: Phase II Study of NGR-hTNF Versus Placebo as Maintenance Treatment in Patients With Advanced MPM
Official title: NGR019: Randomized Double-blind Phase II Study of NGR-hTNF Versus Placebo as Maintenance Treatment in Patients With Advanced Malignant Pleural Mesothelioma (MPM)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Advanced Malignant Pleural Mesothelioma
Keywords: Malignant Pleural Mesothelioma
MPM
Maintenance treatment
NGR-hTNF
Lead sponsor: AGC Biologics S.p.A.
Sponsor class: INDUSTRY
First posted: 2011-05-23
Enrollment: 137
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* 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:

  1. Neutrophils ≥ 1.5 x 109/L; platelets ≥ 100 x109/L; hemoglobin ≥ 9 g/dL
  2. Bilirubin ≤ 1.5 x ULN
  3. AST and/or ALT ≤ 2.5 x ULN in absence of liver metastasis or ≤ 5 x ULN in presence of liver metastasis
  4. 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

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: every 6 weeks
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: every 6-12 weeks
measure: Tumor response
timeFrame: every 6 weeks
measure: Safety and Toxicity according to NCI-CTCAE criteria(version 4.03)
timeFrame: during the study
measure: Quality of life assessment by using a questionnaire according to Lung Cancer Symptom Scale (LCSS)
timeFrame: From date of randomization until the end of treatment, assessed every 6 weeks
Other outcomes:
Locations:
city: Bad Berka
country: Germany
facility: Zentralklinik Bad Berka GmbH
state: Thuringia
city: München-Gauting
country: Germany
facility: Asklepios Fachkliniken München-Gauting
city: Casale Monferrato
country: Italy
facility: Ospedale Santo Spirito
state: Alessandria
city: Meldola
country: Italy
facility: Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori-IRST
state: Forlì-Cesena
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
state: Milan
city: Alessandria
country: Italy
facility: Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo di Alessandria
city: Genoa
country: Italy
facility: IRCCS Azienda Ospedaliera Universitaria San Martino IST Istituto Nazionale per la Ricerca sul Cancro
city: Genova
country: Italy
facility: Asl 3 genovese, Ospedale Villa Scassi
city: Milano
country: Italy
facility: IRCCS Ospedale San Raffaele
city: Padova
country: Italy
facility: Istituto Oncologico Veneto
city: Parma
country: Italy
facility: Azienda Ospedaliero-Universitaria di Parma
city: Pavia
country: Italy
facility: IRCCS Policlinico S. Matteo
city: Ravenna
country: Italy
facility: Azienda Unità Sanitaria locale di Ravenna
city: Treviso
country: Italy
facility: Ospedale Ca' Foncello
city: Saint-Petersburg
country: Russian Federation
facility: Saint Petersburg State Medical University n.a. I. P. Pavlov
Study officials:
affiliation: AGC Biologics S.p.A.
name: Antonio Lambiase, MD
role: STUDY_DIRECTOR
References: