NGR015: Study in Second Line for Patient With Advanced Malignant Pleural Mesothelioma Pretreated With Pemetrexed - Full Text View

Sponsor:	MolMed S.p.A.
Information provided by (Responsible Party):	MolMed S.p.A.
ClinicalTrials.gov Identifier:	NCT01098266

Purpose

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	Intervention	Phase
Malignant Pleural Mesothelioma	Drug: NGR-hTNF plus Best Investigator Choice (BIC) Drug: Placebo plus Best Investigator Choice (BIC)	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, 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)

Resource links provided by NLM:

MedlinePlus related topics: Cancer Mesothelioma

U.S. FDA Resources

Further study details as provided by MolMed S.p.A.:

Primary Outcome Measures:

Overall Survival (OS) [ Time Frame: every 6-12 weeks ] [ Designated as safety issue: No ]
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:

Progression-Free Survival (PFS) [ Time Frame: every 6-12 weeks ] [ Designated as safety issue: No ]
Defined as the time from the date of randomization until disease progression, or death
Disease Control Rate (DCR) [ Time Frame: every 6-12 weeks ] [ Designated as safety issue: No ]
Defined as the percentage of patients who have a best-response rating of complete response, partial response, or stable disease
Duration of Disease Control [ Time Frame: every 6-12 weeks ] [ Designated as safety issue: No ]
Measured from the date of randomization until disease progression, or death due to any cause
Safety and Toxicity according to NCI-CTCAE criteria (version 4.02) [ Time Frame: every 6-12 weeks ] [ Designated as safety issue: Yes ]
Quality of life (QoL) according to Lung Cancer Symptom Scale [ Time Frame: every 6-12 weeks ] [ Designated as safety issue: No ]
Evaluation of medical care utilization in the two treatment arms [ Time Frame: every 6-12 weeks ] [ Designated as safety issue: No ]
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.

Estimated Enrollment:	390
Study Start Date:	March 2010
Estimated Study Completion Date:	February 2013
Estimated Primary Completion Date:	February 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: A: NGR-hTNF + BIC	Drug: NGR-hTNF plus Best Investigator 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: 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: 25-30 mg/m2 iv (or 60-80 mg/m2 per os) on days 1 and 8, every 3 weeks, for a maximum of 6 cycles (or weekly for 12 weeks)
Placebo Comparator: B: Placebo+BIC	Drug: Placebo plus Best Investigator 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: 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: 25-30 mg/m2 iv (or 60-80 mg/m2 per os) on days 1 and 8, every 3 weeks, for a maximum of 6 cycles (or weekly for 12 weeks)

Arms

Assigned Interventions

Experimental: A: NGR-hTNF + BIC

Drug: NGR-hTNF plus Best Investigator 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: 25-30 mg/m2 iv (or 60-80 mg/m2 per os) on days 1 and 8, every 3 weeks, for a maximum of 6 cycles (or weekly for 12 weeks)

Placebo Comparator: B: Placebo+BIC

Drug: Placebo plus Best Investigator 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: 25-30 mg/m2 iv (or 60-80 mg/m2 per os) on days 1 and 8, every 3 weeks, for a maximum of 6 cycles (or weekly for 12 weeks)

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
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
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 and radiation therapy: wash-out period of 14 days
2. Systemic 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. Patients - both males and females - with reproductive potential (i.e. menopausal for less than 1-year and not surgically sterilized) must practice effective contraceptive measures throughout the study. Women of childbearing potential must provide a negative pregnancy test (serum or urine) within 14 days before the enrolment

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01098266

Contacts

Contact: Federico Caligaris Cappio, MD

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Locations

United States, California
City of Hope-Comprehensive Cancer Cente	Recruiting
Duarte, California, United States, 91010
Contact: Marianna Koczywas, MD
Principal Investigator: Marianna Koczywas, MD
United States, Maryland
Johns Hopkins	Recruiting
Baltimore, Maryland, United States, 21231
Contact: Julie Brahmer, MD
Principal Investigator: Julie Brahmer, MD
United States, New York
Columbia University	Recruiting
New York, New York, United States, 10032
Contact: Robert N. Taub, MD
Principal Investigator: Robert N Taub, MD
United States, Texas
UTsouthwestern medical center	Recruiting
Dallas, Texas, United States, 75390
Contact: Jonathan Dowell, MD
Principal Investigator: Jonathan Dowell, MD
Canada, Alberta
UAB - Alberta Cancer Board - Cross Cancer Institute	Recruiting
Edmonton, Alberta, Canada, T6G1Z2
Contact: Quincy Chu, MD
Principal Investigator: Quincy Chu, MD
Egypt
National Cancer Institute	Recruiting
Cairo, Egypt, 11796
Contact: Rabab M. Gaafar, MD
Principal Investigator: Rabab M Gaafar, MD
Ireland
St James's Hospital	Recruiting
Dublin, Ireland
Contact: Ken O'Byrne, MD
Principal Investigator: Ken O'Byrne, MD
Italy
Ospedale Santo Spirito	Recruiting
Monferrato, Alessandria, Italy, 15033
Contact: Mario Botta, MD
Principal Investigator: Mario Botta, MD
Azienda Ospedaliera Universitaria San Luigi Gonzaga	Recruiting
Orbassano, Torino, Italy, 10043
Contact: Silvia Novello, MD
Principal Investigator: Silvia Novello, MD
Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo di Alessandria	Not yet recruiting
Alessandria, Italy, 15100
Contact: Federica Grosso, MD
Principal Investigator: Federica Grosso, MD
Centro di Riferimento Oncologico	Recruiting
Aviano, Italy
Contact: Alessandra Bearz, MD 0
Principal Investigator: Alessandra Bearz, MD
Ospedale Valduce	Recruiting
Como, Italy
Contact: Clelia Casartelli, MD 0
Principal Investigator: Clelia Casartelli, MD
Azienda Ospedaliero-Universitaria Careggi di Firenze	Completed
Firenze, Italy
Istituto Nazionale per la Ricerca sul Cancro	Recruiting
Genoa, Italy, 16132
Contact: Francesco Grossi, MD
Principal Investigator: Francesco Grossi, MD
Fondazione San Raffaele del Monte Tabor	Recruiting
Milan, Italy, 20132
Contact: Federico Caligaris Cappio, MD
Sub-Investigator: Vanesa Gregorc, MD
Azienda Ospedaliera San Gerardo	Recruiting
Monza, Italy, 20052
Contact: Paolo Bidoli, MD
Principal Investigator: Paolo Bidoli, MD
Istituto Oncologico Veneto	Recruiting
Padova, Italy
Contact: Adolfo Favaretto, MD
Principal Investigator: Adolfo Favaretto, MD
Azienda Ospedaliero Universitaria di Parma	Recruiting
Parma, Italy
Contact: Marcello Tiseo, MD 0
Principal Investigator: Marcello Tiseo, MD
A.O. Salvini Garbagnate, Ospedale di Rho	Recruiting
Rho, Italy
Contact: Roberto Bolina, MD 0
Principal Investigator: Roberto Bollina, MD
Poland
Medical University of Gdansk	Recruiting
Gdansk, Poland, 80211
Contact: Jacek Jassem, MD
Principal Investigator: Jacek Jassem, MD
Maria Sklodowska Memorial Cancer Center and Institute of Oncology	Recruiting
Warsaw, Poland, 02-781
Contact: Pawel Badurak, MD
Principal Investigator: Pawel Badurak, MD
United Kingdom
Kent Oncology Centre Maidstone Hospital	Recruiting
Maidstone, Kent, United Kingdom, ME16 9QQ
Contact: Ryaz Shah, MD
Principal Investigator: Ryaz Shah, MD
Mount Vernon Cancer Centre	Recruiting
Middlesex, Northwood, United Kingdom, HA6 2RN
Contact: Andreas Polychronis
Principal Investigator: Andreas Polychronis, MD
The Royal Marsden Hospital	Recruiting
Sutton, Surrey, United Kingdom
Contact: Mary O'Brien, MD
Principal Investigator: Mary O'Brien, MD
Guy's Hospital	Recruiting
London, United Kingdom, SE1 9RT
Contact: Rohit Lal
Principal Investigator: Rohit Lal, MD
The Royal Marsden Hospital	Recruiting
London, United Kingdom, SW3 6JJ
Contact: Mary O'Brien, MD
Principal Investigator: Mary O'Brien, MD

Sponsors and Collaborators

MolMed S.p.A.

Investigators

Study Director:

Antonio Lambiase, MD

MolMed S.p.A.

More Information

No publications provided

Responsible Party:	MolMed S.p.A.
ClinicalTrials.gov Identifier:	NCT01098266 History of Changes
Other Study ID Numbers:	NGR015, 2009-016879-29
Study First Received:	March 17, 2010
Last Updated:	December 30, 2011
Health Authority:	Italy: Ethics Committee United States: Food and Drug Administration United Kingdom: Medicines and Healthcare Products Regulatory Agency Poland: The Central Register of Clinical Trials Austria: Austrian Competent Authority Ireland: Irish Medicines Board Canada: Health Canada Egypt: Ministry of Health Belgium: Centrale Commissie Mensgebonden Onderzoek

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

ClinicalTrials.gov processed this record on May 23, 2012