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

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ClinicalTrials.gov Identifier: NCT01098266
Recruitment Status : Completed
First Posted : April 2, 2010
Last Update Posted : December 22, 2017
Sponsor:
Information provided by (Responsible Party):
MolMed S.p.A.

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.

Condition or disease Intervention/treatment Phase
Malignant Pleural Mesothelioma Drug: NGR-hTNF plus Best Investigator's Choice (BIC) Drug: Placebo plus Best Investigator's Choice (BIC) Phase 3

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 Type : Interventional  (Clinical Trial)
Actual Enrollment : 400 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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)
Study Start Date : March 2010
Actual Primary Completion Date : December 2017
Actual Study Completion Date : December 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Mesothelioma

Arm Intervention/treatment
Experimental: A: NGR-hTNF + BIC
NGR-hTNF plus Best Investigator's Choice
Drug: NGR-hTNF plus Best Investigator's Choice (BIC)
  • 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)
Other Name: NGR-hTNF+BIC

Placebo Comparator: B: Placebo+BIC
Placebo plus Best Investigator's Choice
Drug: Placebo plus Best Investigator's Choice (BIC)
  • 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)
Other Name: Placebo+BIC




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. Progression-Free Survival (PFS) [ Time Frame: every 6-12 weeks ]
    Defined as the time from the date of randomization until disease progression, or death

  2. Disease Control Rate (DCR) [ Time Frame: every 6-12 weeks ]
    Defined as the percentage of patients who have a best-response rating of complete response, partial response, or stable disease

  3. Duration of Disease Control [ Time Frame: every 6-12 weeks ]
    Measured from the date of randomization until disease progression, or death due to any cause

  4. Safety and Toxicity according to NCI-CTCAE criteria (version 4.02) [ Time Frame: every 6-12 weeks ]
  5. Quality of life (QoL) according to Lung Cancer Symptom Scale [ Time Frame: every 6-12 weeks ]
  6. Evaluation of medical care utilization in the two treatment arms [ Time Frame: every 6-12 weeks ]
    Medical resource use data collected will be used in health economic analyses where it may be combined with other data from other sources such as cost data or other clinical parameters.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01098266


  Show 49 Study Locations
Sponsors and Collaborators
MolMed S.p.A.
Investigators
Study Director: Antonio Lambiase, MD MolMed S.p.A.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: MolMed S.p.A.
ClinicalTrials.gov Identifier: NCT01098266     History of Changes
Other Study ID Numbers: NGR015
2009-016879-29 ( EudraCT Number )
First Posted: April 2, 2010    Key Record Dates
Last Update Posted: December 22, 2017
Last Verified: December 2017

Keywords provided by MolMed S.p.A.:
MPM
NGR-hTNF
NGR-hTNF plus BIC
Randomized double-blind phase III study

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