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

NCT ID: NCT01358084

Last Updated: 2019-01-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 137 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-03-31
• Study Completion Date: 2018-12-05

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.

Conditions

Advanced Malignant Pleural Mesothelioma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Arm A: NGR-hTNF + Best Supportive Care

NGR-hTNF + Best Supportive Care

Group Type: EXPERIMENTAL

NGR-hTNF

Intervention Type: DRUG

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

Best Supportive Care

Intervention Type: OTHER

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

Arm B: Placebo + Best Supportive Care

Placebo + Best Supportive Care

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Best Supportive Care

Intervention Type: OTHER

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

Interventions

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

Intervention Type: DRUG

Placebo

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

Intervention Type: DRUG

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

Intervention Type: OTHER

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AGC Biologics S.p.A.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Antonio Lambiase, MD

Role: STUDY_DIRECTOR

AGC Biologics S.p.A.

Locations

IRCCS Policlinico S. Matteo

Pavia, , Italy

Zentralklinik Bad Berka GmbH

Bad Berka, Thuringia, Germany

Asklepios Fachkliniken München-Gauting

München-Gauting, , Germany

Ospedale Santo Spirito

Casale Monferrato, Alessandria, Italy

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori-IRST

Meldola, Forlì-Cesena, Italy

Istituto Clinico Humanitas

Rozzano, Milan, Italy

Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo di Alessandria

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

IRCCS Ospedale San Raffaele

Milan, , Italy

Istituto Oncologico Veneto

Padua, , Italy

Azienda Ospedaliero-Universitaria di Parma

Parma, , Italy

Azienda Unità Sanitaria locale di Ravenna

Ravenna, , Italy

Ospedale Ca' Foncello

Treviso, , Italy

Saint Petersburg State Medical University n.a. I. P. Pavlov

Saint Petersburg, , Russia

Countries

Germany; Italy; Russia

Other Identifiers

2010-023614-31

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

NGR019

Identifier Type: -

Identifier Source: org_study_id