NGR015: Study in Second Line for Patient With Advanced Malignant Pleural Mesothelioma Pretreated With Pemetrexed

Brief Title

NGR015: Study in Second Line for Patient With Advanced Malignant Pleural Mesothelioma Pretreated With Pemetrexed

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)

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.
    

Study Phase

Phase 3

Study Type

Interventional

Primary Outcome

Overall Survival (OS)

Secondary Outcome

 Progression-Free Survival (PFS)

Condition

Malignant Pleural Mesothelioma

Intervention

NGR-hTNF plus Best Investigator's Choice (BIC)

Study Arms / Comparison Groups

 A: NGR-hTNF + BIC

Description:  NGR-hTNF plus Best Investigator's Choice

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Drug

Estimated Enrollment

400

Start Date

April 12, 2010

Completion Date

December 2017

Primary Completion Date

April 29, 2014

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

          -  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
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Antonio Lambiase, MD, , 

Location Countries

Belgium

Location Countries

Belgium

NCT ID

NCT01098266

Organization ID

NGR015

Secondary IDs

2009-016879-29

Responsible Party

Sponsor

Study Sponsor

AGC Biologics S.p.A.

Study Sponsor

Antonio Lambiase, MD, Study Director, AGC Biologics S.p.A.

Verification Date

August 2019