Clinical trial NCT01098266
Conditions: Malignant Pleural Mesothelioma
Keywords: MPM NGR-hTNF NGR-hTNF plus BIC Randomized double-blind phase III study
Sponsor: AGC Biologics S.p.A.
Start date: 2010-04-12; Completion date: 2017-12-01
Enrollment: 400 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief 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.

Detailed 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.

Arms: arm 1: NGR-hTNF plus Best Investigator's Choice arm 2: Placebo plus Best Investigator's Choice
Interventions: intervention 1: NGR-hTNF plus Best Investigator's Choice (BIC) intervention 2: Placebo plus Best Investigator's Choice (BIC)
Intervention descriptions: intervention 1: * 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:

  1. Doxorubicin: 60-75 mg/m2 every 3 weeks, for a maximum of 6 cycles
  2. Gemcitabine: 1,000-1,250 mg/m2 on days 1 and 8, every 3 weeks, for a maximum of 6 cycles
  3. 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) intervention 2: * 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:

  1. Doxorubicin: 60-75 mg/m2 every 3 weeks, for a maximum of 6 cycles
  2. Gemcitabine: 1,000-1,250 mg/m2 on days 1 and 8, every 3 weeks, for a maximum of 6 cycles
  3. 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)

Protocol documents: