Phase II Study of NGR-hTNF Versus Placebo as Maintenance Treatment in Patients With Advanced MPM

Advanced Malignant Pleural Mesothelioma Clinical Trial

— NGR019  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01358084
• Other study ID #: NGR019
• Secondary ID: 2010-023614-31
• Status: Completed
• Phase: Phase 2
• Start date: March 2011
• Est. completion date: December 5, 2018

Study information

• Verified date: January 2019
• Source: MolMed S.p.A.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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 information / eligibility

• Status: Completed
• Enrollment: 137
• Est. completion date: December 5, 2018
• Est. primary completion date: December 5, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Malignant Pleural Mesothelioma
• Mesothelioma

Intervention

Drug:
• NGR-hTNF
NGR-hTNF: 0.8 mcg/m² as 60-minute intravenous infusion every week until confirmed evidence of disease progression or unacceptable toxicity occurs
• Placebo
Placebo: 0.8 mcg/m² as 60-minute intravenous infusion every week until confirmed evidence of disease progression or unacceptable toxicity occurs

Other:
• Best Supportive Care
Where applicable and as appropriate according to Institutional clinical practice and literature guidelines. Best supportive care includes antibiotics, analgesics, antiemetics, thoracentesis, pleurodesis, blood transfusions, nutritional support, and focal external-beam radiation for control of pain, cough, dyspnea, or hemoptysis

Locations

Country	Name	City	State
Germany	Zentralklinik Bad Berka GmbH	Bad Berka	Thuringia
Germany	Asklepios Fachkliniken München-Gauting	München-Gauting
Italy	Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo di Alessandria	Alessandria
Italy	Ospedale Santo Spirito	Casale Monferrato	Alessandria
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 Scientifico Romagnolo per lo Studio e la Cura dei Tumori-IRST	Meldola	Forlì-Cesena
Italy	IRCCS Ospedale San Raffaele	Milano
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	Istituto Clinico Humanitas	Rozzano	Milan
Italy	Ospedale Ca' Foncello	Treviso
Russian Federation	Saint Petersburg State Medical University n.a. I. P. Pavlov	Saint-Petersburg

Sponsors (1)

Lead Sponsor	Collaborator
MolMed S.p.A.

Countries where clinical trial is conducted

Germany,  Italy,  Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-Free Survival (PFS)	Defined as the time from the date of randomization until disease progression, or death	every 6 weeks
Secondary	Overall survival (OS)	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	every 6-12 weeks
Secondary	Tumor response	Assessed according to modified RECIST criteria for MPM	every 6 weeks
Secondary	Safety and Toxicity according to NCI-CTCAE criteria(version 4.03)	To evaluate safety and toxicity profile related to NGR-hTNF	during the study
Secondary	Quality of life assessment by using a questionnaire according to Lung Cancer Symptom Scale (LCSS)	To assess changes in quality of life (QoL) in the two treatment arms.	From date of randomization until the end of treatment, assessed every 6 weeks