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

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ClinicalTrials.gov Identifier: NCT01358084
Recruitment Status : Completed
First Posted : May 23, 2011
Last Update Posted : January 15, 2019
Sponsor:
Information provided by (Responsible Party):
MolMed S.p.A.

Tracking Information
First Submitted Date  ICMJE May 19, 2011
First Posted Date  ICMJE May 23, 2011
Last Update Posted Date January 15, 2019
Study Start Date  ICMJE March 2011
Actual Primary Completion Date December 5, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 20, 2011)
Progression-Free Survival (PFS) [ Time Frame: every 6 weeks ]
Defined as the time from the date of randomization until disease progression, or death
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01358084 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 28, 2018)
  • 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
  • Tumor response [ Time Frame: every 6 weeks ]
    Assessed according to modified RECIST criteria for MPM
  • 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
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 20, 2011)
  • 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
  • Tumor response [ Time Frame: every 6 weeks ]
    Assessed according to modified RECIST criteria for MPM
  • Safety and Toxicity according to NCI-CTCAE criteria(version 4.03) [ Time Frame: during the study ]
  • Quality of life (QoL) according to Lung Cancer Symptom Scale [ Time Frame: every 6-12 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase II Study of NGR-hTNF Versus Placebo as Maintenance Treatment in Patients With Advanced MPM
Official Title  ICMJE NGR019: Randomized Double-blind Phase II Study of NGR-hTNF Versus Placebo as Maintenance Treatment in Patients With Advanced Malignant Pleural Mesothelioma (MPM)
Brief Summary 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
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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Advanced Malignant Pleural Mesothelioma
Intervention  ICMJE
  • 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
  • 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
Study Arms  ICMJE
  • Experimental: Arm A: NGR-hTNF + Best Supportive Care
    NGR-hTNF + Best Supportive Care
    Interventions:
    • Drug: NGR-hTNF
    • Other: Best Supportive Care
  • Placebo Comparator: Arm B: Placebo + Best Supportive Care
    Placebo + Best Supportive Care
    Interventions:
    • Drug: Placebo
    • Other: Best Supportive Care
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 14, 2019)
137
Original Estimated Enrollment  ICMJE
 (submitted: May 20, 2011)
100
Actual Study Completion Date  ICMJE December 5, 2018
Actual Primary Completion Date December 5, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany,   Italy,   Russian Federation
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01358084
Other Study ID Numbers  ICMJE NGR019
2010-023614-31 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party MolMed S.p.A.
Study Sponsor  ICMJE MolMed S.p.A.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Antonio Lambiase, MD MolMed S.p.A.
PRS Account MolMed S.p.A.
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP