Back to resultsPhase II Study of NGR-hTNF Versus Placebo as Maintenance Treatment in Patients With Advanced MPM (NGR019)
Primary Purpose
Advanced Malignant Pleural Mesothelioma
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
NGR-hTNF
Placebo
Best Supportive Care
Sponsored by
About this trial
This is an interventional treatment trial for Advanced Malignant Pleural Mesothelioma focused on measuring Malignant Pleural Mesothelioma, MPM, Maintenance treatment, NGR-hTNF
Eligibility 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
- ECOG Performance Status 0 - 1
- Life expectancy of ≥ 12 weeks
Adequate baseline bone marrow, hepatic and renal function, defined as follows:
- Neutrophils ≥ 1.5 x 109/L; platelets ≥ 100 x109/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 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.
Sites / Locations
- Zentralklinik Bad Berka GmbH
- Asklepios Fachkliniken München-Gauting
- Ospedale Santo Spirito
- Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori-IRST
- Istituto Clinico Humanitas
- Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo di Alessandria
- IRCCS Azienda Ospedaliera Universitaria San Martino IST Istituto Nazionale per la Ricerca sul Cancro
- Asl 3 genovese, Ospedale Villa Scassi
- IRCCS Ospedale San Raffaele
- Istituto Oncologico Veneto
- Azienda Ospedaliero-Universitaria di Parma
- IRCCS Policlinico S. Matteo
- Azienda Unità Sanitaria locale di Ravenna
- Ospedale Ca' Foncello
- Saint Petersburg State Medical University n.a. I. P. Pavlov
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Arm A: NGR-hTNF + Best Supportive Care
Arm B: Placebo + Best Supportive Care
Arm Description
NGR-hTNF + Best Supportive Care
Placebo + Best Supportive Care
Outcomes
Primary Outcome Measures
Progression-Free Survival (PFS)
Defined as the time from the date of randomization until disease progression, or death
Secondary Outcome Measures
Overall survival (OS)
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
Assessed according to modified RECIST criteria for MPM
Safety and Toxicity according to NCI-CTCAE criteria(version 4.03)
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)
To assess changes in quality of life (QoL) in the two treatment arms.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01358084
Brief Title
Phase II Study of NGR-hTNF Versus Placebo as Maintenance Treatment in Patients With Advanced MPM
Acronym
NGR019
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)
Study Type
Interventional
2. Study Status
Record Verification Date
January 2019
Overall Recruitment Status
Completed
Study Start Date
March 2011 (undefined)
Primary Completion Date
December 5, 2018 (Actual)
Study Completion Date
December 5, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AGC Biologics S.p.A.
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Malignant Pleural Mesothelioma
Keywords
Malignant Pleural Mesothelioma, MPM, Maintenance treatment, NGR-hTNF
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
137 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm A: NGR-hTNF + Best Supportive Care
Arm Type
Experimental
Arm Description
NGR-hTNF + Best Supportive Care
Arm Title
Arm B: Placebo + Best Supportive Care
Arm Type
Placebo Comparator
Arm Description
Placebo + Best Supportive Care
Intervention Type
Drug
Intervention Name(s)
NGR-hTNF
Intervention Description
NGR-hTNF: 0.8 mcg/m² as 60-minute intravenous infusion every week until confirmed evidence of disease progression or unacceptable toxicity occurs
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo: 0.8 mcg/m² as 60-minute intravenous infusion every week until confirmed evidence of disease progression or unacceptable toxicity occurs
Intervention Type
Other
Intervention Name(s)
Best Supportive Care
Intervention Description
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
Primary Outcome Measure Information:
Title
Progression-Free Survival (PFS)
Description
Defined as the time from the date of randomization until disease progression, or death
Time Frame
every 6 weeks
Secondary Outcome Measure Information:
Title
Overall survival (OS)
Description
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
Time Frame
every 6-12 weeks
Title
Tumor response
Description
Assessed according to modified RECIST criteria for MPM
Time Frame
every 6 weeks
Title
Safety and Toxicity according to NCI-CTCAE criteria(version 4.03)
Description
To evaluate safety and toxicity profile related to NGR-hTNF
Time Frame
during the study
Title
Quality of life assessment by using a questionnaire according to Lung Cancer Symptom Scale (LCSS)
Description
To assess changes in quality of life (QoL) in the two treatment arms.
Time Frame
From date of randomization until the end of treatment, assessed every 6 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
ECOG Performance Status 0 - 1
Life expectancy of ≥ 12 weeks
Adequate baseline bone marrow, hepatic and renal function, defined as follows:
Neutrophils ≥ 1.5 x 109/L; platelets ≥ 100 x109/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 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Antonio Lambiase, MD
Organizational Affiliation
AGC Biologics S.p.A.
Official's Role
Study Director
Facility Information:
Facility Name
Zentralklinik Bad Berka GmbH
City
Bad Berka
State/Province
Thuringia
ZIP/Postal Code
99437
Country
Germany
Facility Name
Asklepios Fachkliniken München-Gauting
City
München-Gauting
ZIP/Postal Code
82131
Country
Germany
Facility Name
Ospedale Santo Spirito
City
Casale Monferrato
State/Province
Alessandria
ZIP/Postal Code
15033
Country
Italy
Facility Name
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori-IRST
City
Meldola
State/Province
Forlì-Cesena
ZIP/Postal Code
47014
Country
Italy
Facility Name
Istituto Clinico Humanitas
City
Rozzano
State/Province
Milan
ZIP/Postal Code
20089
Country
Italy
Facility Name
Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo di Alessandria
City
Alessandria
ZIP/Postal Code
15121
Country
Italy
Facility Name
IRCCS Azienda Ospedaliera Universitaria San Martino IST Istituto Nazionale per la Ricerca sul Cancro
City
Genoa
ZIP/Postal Code
16132
Country
Italy
Facility Name
Asl 3 genovese, Ospedale Villa Scassi
City
Genova
ZIP/Postal Code
16149
Country
Italy
Facility Name
IRCCS Ospedale San Raffaele
City
Milano
ZIP/Postal Code
20132
Country
Italy
Facility Name
Istituto Oncologico Veneto
City
Padova
ZIP/Postal Code
35128
Country
Italy
Facility Name
Azienda Ospedaliero-Universitaria di Parma
City
Parma
ZIP/Postal Code
43126
Country
Italy
Facility Name
IRCCS Policlinico S. Matteo
City
Pavia
ZIP/Postal Code
27100
Country
Italy
Facility Name
Azienda Unità Sanitaria locale di Ravenna
City
Ravenna
ZIP/Postal Code
48121
Country
Italy
Facility Name
Ospedale Ca' Foncello
City
Treviso
ZIP/Postal Code
31100
Country
Italy
Facility Name
Saint Petersburg State Medical University n.a. I. P. Pavlov
City
Saint-Petersburg
ZIP/Postal Code
197089
Country
Russian Federation
12. IPD Sharing Statement
Learn more about this trial
Phase II Study of NGR-hTNF Versus Placebo as Maintenance Treatment in Patients With Advanced MPM
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