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Completed

NCT Number: NCT01098266

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

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.

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Key information

Conditions

Malignant Pleural Mesothelioma Adenoma Lung Diseases Lung Neoplasms Mesothelioma Mesothelioma, Malignant Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Glandular and Epithelial Neoplasms, Mesothelial Pleural Neoplasms Respiratory Tract Diseases Respiratory Tract Neoplasms Thoracic Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Antwerp University Hospital, Edegem, Antwerp, Belgium

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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:
  • Neutrophils ≥ 1.5 x 109/L; platelets ≥ 100 x 109/L; hemoglobin ≥ 9 g/dL
  • Bilirubin ≤ 1.5 x ULN
  • AST and/or ALT ≤ 2.5 x ULN in absence of liver metastasis or ≤ 5 x ULN in presence of liver metastasis
  • 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:
  • Surgery: wash-out period of 14 days
  • 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

Treatment and study plan

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

Drug
  • 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:
  • Doxorubicin: 60-75 mg/m2 every 3 weeks, for a maximum of 6 cycles
  • Gemcitabine: 1,000-1,250 mg/m2 on days 1 and 8, every 3 weeks, for a maximum of 6 cycles
  • 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 names: NGR-hTNF+BIC

Placebo plus Best Investigator's Choice (BIC)

Drug
  • 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:
  • Doxorubicin: 60-75 mg/m2 every 3 weeks, for a maximum of 6 cycles
  • Gemcitabine: 1,000-1,250 mg/m2 on days 1 and 8, every 3 weeks, for a maximum of 6 cycles
  • 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 names: Placebo+BIC

Primary outcomes

  1. Overall Survival (OS)

    Time frame: From date of randomization until the date of first documented progression or date of death from any cause, wichever came first, assesed up to 48 months

    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 outcomes

  1. Progression-Free Survival (PFS)

    Time frame: From the date of randomization until the date of first documented progression or date of death from any cause, wichever came first, assessed up to 48 months

    Defined as the time from the date of randomization until disease progression, or deathdue to any couse or the last patient was konwn to be alive. Progression is defined usind Response Evaluation Criteria In Solid Tumors Criteria (Recist v1.1), as a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition torelative increase of 20% the sum must also demonstrate an absolute increase of at least 5 mm. In addition the appearance of one or more new lesions was also considered progression

  2. Disease Control Rate (DCR)

    Time frame: Assessed every 6-12 weeks, up to 100 weeks

    Disease control rate (DCR), defined as the percentage of patients who have a best-response rating of complete or partial response or stable disease, according to MPM-modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria

  3. Number of Partecipants With Disease Control for ≥ 6 Months

    Time frame: Assessed every 6-12 weeks, up to 100 weeks

    Measured from the date of randomization until disease progression, or death due to any cause

  4. Number of Partecipants With Adverse Events

    Time frame: Assessed every 6-12 weeks, up to 100 weeks

    All adverse events will be recorded according to CTC version 4.02 (CTC reference: http://ctep.cancer.gov/reporting/ctc.html) on the case report forms (CRFs); the investigator will decide if those events are drug related and his decision will be recorded on the forms for all adverse events.

  5. Time to LCSS Symptomatic Progression

    Time frame: from the date of randomization to the date of the LCSS assessment on which symptomatic progression was identified, assessed on cycle 2, cycle 4 and cycle 6 (each cycle lasted 21 days)

    Quality of life (QoL) assessment was performed by using a questionnaire according to The Lung Cancer Symptom Scale (LCSS) . The LCSS is designed as a disease and site-specific measure of QoL particularly for use in clinical trials. It evaluates six major symptoms (loss of appetite, fatigue, cough, dyspnea, hemoptysis, and pain) associated with lung malignancies and their effect on overall symptomatic distress, functional activities, and global QoL. Within this trial the questionnaire according to LCSS was only recorded by the patient (patient's scale). QoL assessment was performed by using a questionnaire according to LCSS, which consists of nine 100-mm visual analog scales, with scores reported from 0 to 100 (0 representing the best score). The LCSS subscore is the average symptom burden index computed as the mean score for all six major symptoms. Symptomatic progression was defined as a worsening in the average symptom burden index by 25%.

  6. Evaluation of Medical Care Utilization in the Two Treatment Arms

    Time frame: Assessed every 6-12 weeks, up to 100 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.

Sponsors and collaborators

Lead sponsor

AGC Biologics S.p.A.

Industry

Registry information

Official study 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)

Important dates

Study start
2010
Primary completion
2014
Study completion
2017
First posted
Apr 2, 2010
Registry last updated
Sep 17, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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