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

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2013 by MolMed S.p.A.
Sponsor:
Information provided by (Responsible Party):
MolMed S.p.A.
ClinicalTrials.gov Identifier:
NCT01358084
First received: May 19, 2011
Last updated: January 28, 2013
Last verified: January 2013
  Purpose

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


Condition Intervention Phase
Advanced Malignant Pleural Mesothelioma
Drug: NGR-hTNF
Drug: Placebo
Other: Best Supportive Care
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: NGR019: Randomized Double-blind Phase II Study of NGR-hTNF Versus Placebo as Maintenance Treatment in Patients With Advanced Malignant Pleural Mesothelioma (MPM)

Resource links provided by NLM:


Further study details as provided by MolMed S.p.A.:

Primary Outcome Measures:
  • Progression-Free Survival (PFS) [ Time Frame: every 6 weeks ] [ Designated as safety issue: No ]
    Defined as the time from the date of randomization until disease progression, or death


Secondary Outcome Measures:
  • Overall survival (OS) [ Time Frame: every 6-12 weeks ] [ Designated as safety issue: No ]
    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

  • Tumor response [ Time Frame: every 6 weeks ] [ Designated as safety issue: No ]
    Assessed according to modified RECIST criteria for MPM

  • Safety and Toxicity according to NCI-CTCAE criteria(version 4.03) [ Time Frame: during the study ] [ Designated as safety issue: Yes ]
  • Quality of life (QoL) according to Lung Cancer Symptom Scale [ Time Frame: every 6-12 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 100
Study Start Date: March 2011
Estimated Study Completion Date: June 2013
Estimated Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A: 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 Drug: Placebo
Placebo: 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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  • Good clinical conditions
  • Adequate baseline bone marrow, hepatic and renal function
  • 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

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01358084

Contacts
Contact: Armando Santoro, MD 0

Locations
Italy
Ospedale Santo Spirito Recruiting
Casale Monferrato, Alessandria, Italy, 15033
Contact: Mario Botta, MD         
Principal Investigator: Mario Botta, MD         
Istituto Clinico Humanitas Recruiting
Rozzano, Milan, Italy, 20089
Principal Investigator: Armando Santoro, MD         
Sub-Investigator: Paolo Zucali, MD         
Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo di Alessandria Recruiting
Alessandria, Italy, 15121
Contact: Federica Grosso, MD         
Principal Investigator: Federica Grosso, MD         
IRCCS Azienda Ospedaliera Universitaria San Martino IST Istituto Nazionale per la Ricerca sul Cancro Not yet recruiting
Genoa, Italy, 16132
Contact: Francesco Grossi, MD         
Principal Investigator: Francesco Grossi, MD         
Asl 3 genovese, Ospedale Villa Scassi Recruiting
Genova, Italy, 16149
Contact: Manlio Mencoboni, MD         
Principal Investigator: Manlio Mencoboni, MD         
Azienda Ospedaliero-Universitaria di Parma Not yet recruiting
Parma, Italy, 43126
Contact: Marcello Tiseo, MD         
Principal Investigator: Marcello Tiseo, MD         
IRCCS Policlinico S. Matteo Recruiting
Pavia, Italy, 27100
Contact: Camillo Porta, MD         
Principal Investigator: Camillo Porta, MD         
Ospedale Ca' Foncello Recruiting
Treviso, Italy, 31100
Contact: Giovanni Rosti, MD         
Principal Investigator: Giovanni Rosti, MD         
Sponsors and Collaborators
MolMed S.p.A.
Investigators
Study Director: Antonio Lambiase, MD MolMed S.p.A.
  More Information

No publications provided

Responsible Party: MolMed S.p.A.
ClinicalTrials.gov Identifier: NCT01358084     History of Changes
Other Study ID Numbers: NGR019, 2010-023614-31
Study First Received: May 19, 2011
Last Updated: January 28, 2013
Health Authority: Italy: Ethics Committee

Keywords provided by MolMed S.p.A.:
Malignant Pleural Mesothelioma
MPM
Maintenance treatment
NGR-hTNF

Additional relevant MeSH terms:
Mesothelioma
Neoplasms, Mesothelial
Adenoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms

ClinicalTrials.gov processed this record on September 18, 2014