Advanced Malignant Pleural MesotheliomaPhase 2NGR019NCT01358084
Phase II Study of NGR-hTNF Versus Placebo as Maintenance Treatment in Patients With Advanced MPM
A Phase 2 study testing NGR-hTNF in people with Advanced Malignant Pleural Mesothelioma, run by AGC Biologics S.p.A. at 15 sites in 3 countries.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Malignant Pleural Mesothelioma
- What is being tested?
- NGR-hTNF
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 137 participants
- Where
- 15 sitesin 3 countries
- Study dates
- Mar 2011to 5 Dec 2018
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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
Who cannot join
- 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
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- 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.
Trial locations and contacts
15 sites in 3 countries.
15 sites in 3 countries
Italy12 sites
Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo di Alessandria
Alessandria, 15121
Ospedale Santo Spirito
Casale Monferrato, Alessandria, 15033
IRCCS Azienda Ospedaliera Universitaria San Martino IST Istituto Nazionale per la Ricerca sul Cancro
Genoa, 16132
Asl 3 genovese, Ospedale Villa Scassi
Genova, 16149
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori-IRST
Meldola, Forlì-Cesena, 47014
IRCCS Ospedale San Raffaele
Milan, 20132
Istituto Oncologico Veneto
Padova, 35128
Azienda Ospedaliero-Universitaria di Parma
Parma, 43126
IRCCS Policlinico S. Matteo
Pavia, 27100
Azienda Unità Sanitaria locale di Ravenna
Ravenna, 48121
Istituto Clinico Humanitas
Rozzano, Milan, 20089
Ospedale Ca' Foncello
Treviso, 31100
Germany2 sites
Zentralklinik Bad Berka GmbH
Bad Berka, Thuringia, 99437
Asklepios Fachkliniken München-Gauting
München-Gauting, 82131
Russia1 site
Saint Petersburg State Medical University n.a. I. P. Pavlov
Saint Petersburg, 197089
About this study
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)
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
Read the 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.
- Conditions
- Advanced Malignant Pleural Mesothelioma
- Being tested
- NGR-hTNF, Placebo, Best Supportive Care
- Keywords
- Malignant Pleural Mesothelioma, MPM, Maintenance treatment, NGR-hTNF
- Medical subject headings
- Mesothelioma, Malignant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NGR-hTNFDrug
NGR-hTNF: 0.8 mcg/m² as 60-minute intravenous infusion every week until confirmed evidence of disease progression or unacceptable toxicity occurs
PlaceboDrug
Placebo: 0.8 mcg/m² as 60-minute intravenous infusion every week until confirmed evidence of disease progression or unacceptable toxicity occurs
Best Supportive CareOther
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 group | Role | What they receive |
|---|---|---|
| Arm A: NGR-hTNF + Best Supportive Care | Experimental | NGR-hTNF + Best Supportive Care Receives: Drug: NGR-hTNF; Other: Best Supportive Care |
| Arm B: Placebo + Best Supportive Care | Placebo comparator | Placebo + Best Supportive Care Receives: Drug: Placebo; Other: Best Supportive Care |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-Free Survival (PFS)
Defined as the time from the date of randomization until disease progression, or death
Measured: every 6 weeks
Secondary outcomes (4)
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
Measured: every 6-12 weeks
Tumor response
Assessed according to modified RECIST criteria for MPM
Measured: every 6 weeks
Safety and Toxicity according to NCI-CTCAE criteria(version 4.03)
To evaluate safety and toxicity profile related to NGR-hTNF
Measured: during the study
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.
Measured: From date of randomization until the end of treatment, assessed every 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 May 2011 (estimated)
- Study startMar 2011
- Primary completion5 Dec 2018
- Study completion5 Dec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Malignant Pleural MesotheliomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 137 participants (actual)
Sponsor and investigators
- Lead sponsor
- AGC Biologics S.p.A.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Antonio Lambiase, MD, Study director, AGC Biologics S.p.A.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01358084
- Sponsor's protocol ID
- NGR019
- Other IDs
- 2010-023614-31
- Acronym
- NGR019
- Status last verified
- Jan 2019
- First submitted
- 19 May 2011
- Last updated
- 15 Jan 2019
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT01358084
- Acronym / sponsor ID
- NGR019 / NGR019
- Conditions
- Advanced Malignant Pleural Mesothelioma
- Keywords
- Malignant Pleural Mesothelioma, MPM, Maintenance treatment, NGR-hTNF
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 137 participants (actual)
- Lead sponsor
- AGC Biologics S.p.A.Industry (pharma, biotech, devices)
- Study start
- Mar 2011
- Primary completion
- 5 Dec 2018 (actual)
- Study completion
- 5 Dec 2018 (actual)
- First posted
- 23 May 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A: NGR-hTNF + Best Supportive Care | Experimental | Drug: NGR-hTNF, Other: Best Supportive CareNGR-hTNF + Best Supportive Care |
| Arm B: Placebo + Best Supportive Care | Placebo comparator | Drug: Placebo, Other: Best Supportive CarePlacebo + Best Supportive Care |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NGR-hTNFNGR-hTNF: 0.8 mcg/m² as 60-minute intravenous infusion every week until confirmed evidence of disease progression or unacceptable toxicity occurs | Drug | Arm A: NGR-hTNF + Best Supportive Care |
| PlaceboPlacebo: 0.8 mcg/m² as 60-minute intravenous infusion every week until confirmed evidence of disease progression or unacceptable toxicity occurs | Drug | Arm B: Placebo + Best Supportive Care |
| Best Supportive CareWhere 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 | Other | Arm A: NGR-hTNF + Best Supportive Care, Arm B: Placebo + Best Supportive Care |
Primary outcome
Progression-Free Survival (PFS)
Time frame: every 6 weeks
Defined as the time from the date of randomization until disease progression, or death
4 secondary outcomes
Overall survival (OS)
Time frame: every 6-12 weeks
Tumor response
Time frame: every 6 weeks
Safety and Toxicity according to NCI-CTCAE criteria(version 4.03)
Time frame: during the study
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jan 2019.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Antonio Lambiase, MD study director
AGC Biologics S.p.A.
15 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing NGR-hTNF in people with Advanced Malignant Pleural Mesothelioma, run by AGC Biologics S.p.A. at 15 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in Italy, Germany, Russia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-Free Survival (PFS) (time frame: every 6 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jan 2019.