Phase II Study of NGR-hTNF Versus Placebo as Maintenance Treatment in Patients With Advanced MPM (NGR019)

January 14, 2019 updated by: AGC Biologics S.p.A.

NGR019: Randomized Double-blind Phase II Study of NGR-hTNF Versus Placebo as Maintenance Treatment in Patients With Advanced Malignant Pleural Mesothelioma (MPM)

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

137

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • München-Gauting, Germany, 82131
        • Asklepios Fachkliniken München-Gauting
    • Thuringia
      • Bad Berka, Thuringia, Germany, 99437
        • Zentralklinik Bad Berka GmbH
  • Italy
      • Alessandria, Italy, 15121
        • Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo di Alessandria
      • Genoa, Italy, 16132
        • IRCCS Azienda Ospedaliera Universitaria San Martino IST Istituto Nazionale per la Ricerca sul Cancro
      • Genova, Italy, 16149
        • Asl 3 genovese, Ospedale Villa Scassi
      • Milano, Italy, 20132
        • IRCCS Ospedale San Raffaele
      • Padova, Italy, 35128
        • Istituto Oncologico Veneto
      • Parma, Italy, 43126
        • Azienda Ospedaliero-Universitaria di Parma
      • Pavia, Italy, 27100
        • IRCCS Policlinico S. Matteo
      • Ravenna, Italy, 48121
        • Azienda Unita Sanitaria Locale di Ravenna
      • Treviso, Italy, 31100
        • Ospedale Ca' Foncello
    • Alessandria
      • Casale Monferrato, Alessandria, Italy, 15033
        • Ospedale Santo Spirito
    • Forlì-Cesena
      • Meldola, Forlì-Cesena, Italy, 47014
        • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori-IRST
    • Milan
      • Rozzano, Milan, Italy, 20089
        • Istituto Clinico Humanitas
  • Russian Federation
      • Saint-Petersburg, Russian Federation, 197089
        • Saint Petersburg State Medical University n.a. I. P. Pavlov

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm A: NGR-hTNF + Best Supportive Care
NGR-hTNF + Best Supportive Care
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
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
Placebo Comparator: Arm B: Placebo + Best Supportive Care
Placebo + Best Supportive Care
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
Drug: Placebo
Placebo: 0.8 mcg/m² as 60-minute intravenous infusion every week until confirmed evidence of disease progression or unacceptable toxicity occurs

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-Free Survival (PFS)
Time Frame: every 6 weeks
Defined as the time from the date of randomization until disease progression, or death
every 6 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival (OS)
Time Frame: every 6-12 weeks
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
Tumor response
Time Frame: every 6 weeks
Assessed according to modified RECIST criteria for MPM
every 6 weeks
Safety and Toxicity according to NCI-CTCAE criteria(version 4.03)
Time Frame: during the study
To evaluate safety and toxicity profile related to NGR-hTNF
during the study
Quality of life assessment by using a questionnaire according to Lung Cancer Symptom Scale (LCSS)
Time Frame: From date of randomization until the end of treatment, assessed every 6 weeks
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

AGC Biologics S.p.A.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2011

Primary Completion (Actual)

December 5, 2018

Study Completion (Actual)

December 5, 2018

Study Registration Dates

First Submitted

May 19, 2011

First Submitted That Met QC Criteria

May 20, 2011

First Posted (Estimate)

May 23, 2011

Study Record Updates

Last Update Posted (Actual)

January 15, 2019

Last Update Submitted That Met QC Criteria

January 14, 2019

Last Verified

January 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NGR019
  • 2010-023614-31 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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