Overview

This trial is active, not recruiting.

Condition malignant pleural mesothelioma
Treatments ngr-htnf plus best investigator's choice (bic), placebo plus best investigator's choice (bic)
Phase phase 3
Sponsor MolMed S.p.A.
Start date March 2010
End date December 2016
Trial size 390 participants
Trial identifier NCT01098266, 2009-016879-29, NGR015

Summary

The main objective of the trial is to document the efficacy of NGR-hTNF administered at low dose weekly in advanced Malignant Pleural Mesothelioma patients previously treated with a pemetrexed-based chemotherapy regimen.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Experimental)
NGR-hTNF plus Best Investigator's Choice
ngr-htnf plus best investigator's choice (bic) NGR-hTNF+BIC
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: antibiotics, analgesics, antiemetics, thoracentesis, pleurodesis, blood transfusions, nutritional support, and focal external-beam radiation for control of pain, cough, dyspnea, or hemoptysis Investigator's Choice: one of the following single-agent chemotherapy might be administered in combination: Doxorubicin: 60-75 mg/m2 every 3 weeks, for a maximum of 6 cycles Gemcitabine: 1,000-1,250 mg/m2 on days 1 and 8, every 3 weeks, for a maximum of 6 cycles Vinorelbine: 25 mg/m2 iv (or 60 mg/m2 per os) on days 1 and 8, every 3 weeks, for a maximum of 6 cycles (or weekly for 12 weeks)
(Placebo Comparator)
Placebo plus Best Investigator's Choice
placebo plus best investigator's choice (bic) Placebo+BIC
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: antibiotics, analgesics, antiemetics, thoracentesis, pleurodesis, blood transfusions, nutritional support, and focal external-beam radiation for control of pain, cough, dyspnea, or hemoptysis Investigator's Choice: one of the following single-agent chemotherapy might be administered in combination: Doxorubicin: 60-75 mg/m2 every 3 weeks, for a maximum of 6 cycles Gemcitabine: 1,000-1,250 mg/m2 on days 1 and 8, every 3 weeks, for a maximum of 6 cycles Vinorelbine: 25 mg/m2 iv (or 60 mg/m2 per os) on days 1 and 8, every 3 weeks, for a maximum of 6 cycles (or weekly for 12 weeks)

Primary Outcomes

Measure
Overall Survival (OS)
time frame: every 6-12 weeks

Secondary Outcomes

Measure
Progression-Free Survival (PFS)
time frame: every 6-12 weeks
Disease Control Rate (DCR)
time frame: every 6-12 weeks
Duration of Disease Control
time frame: every 6-12 weeks
Safety and Toxicity according to NCI-CTCAE criteria (version 4.02)
time frame: every 6-12 weeks
Quality of life (QoL) according to Lung Cancer Symptom Scale
time frame: every 6-12 weeks
Evaluation of medical care utilization in the two treatment arms
time frame: every 6-12 weeks

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Age ≥ 18 years - Histologically or cytological confirmed malignant pleural mesothelioma of any of the following subtype: epithelial, sarcomatoid, mixed, or unknown - Prior treatment with no more than one systemic pemetrexed-based chemotherapy regimen administered for advanced or metastatic disease. Prior use of a biological agent in combination with a pemetrexed-based regimen and prior administration of intrapleural cytotoxic agents are allowed. Patients who have previously received anthracyclines should not receive doxorubicin - ECOG Performance Status 0 - 2 - 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 x 109/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 MPM-modified RECIST criteria - Patients may have had prior therapy providing the following conditions are met: 1. Surgery: wash-out period of 14 days 2. Systemic and radiation anti-tumor therapy: wash-out period of 28 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 CNS disease unless adequately treated (e.g., primary brain tumor, any brain metastasis, seizure not controlled with standard medical therapy, or history of stroke) - 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

Additional Information

Official title NGR015: Randomized Double-blind Phase III Study of NGR-hTNF Plus Best Investigator's Choice (BIC) Versus Placebo Plus BIC in Previously Treated Patients With Advanced Malignant Pleural Mesothelioma (MPM)
Description Currently, there are no regulatory-approved or widely accepted treatment options for patients failing a standard pemetrexed-based chemotherapy regimen. For this reason, the best supportive care (BSC) alone might be considered as a standard reference for a randomized phase III trial in this setting. However, single-agent chemotherapeutic agents (such as doxorubicin,gemcitabine, or vinorelbine) with a well-documented safety profile and antitumor activity are also used in clinical practice. Therefore, the best investigator's choice (BIC) between either best supportive care alone or combined with a few selected single-agent chemotherapy (including doxorubicin, gemcitabine, or vinorelbine) might be considered as an acceptable reference arm as well in this setting. The current phase III study aims to show a superior efficacy in terms of overall survival duration of NGR-hTNF 0.8 µg/mq weekly plus BIC versus placebo plus BIC in advanced MPM patients progressing after a standard pemetrexed-based chemotherapy.
Trial information was received from ClinicalTrials.gov and was last updated in October 2015.
Information provided to ClinicalTrials.gov by MolMed S.p.A..