Phase II Study of NGR-hTNF in Combination With Doxorubicin in Patients Affected by Soft Tissue Sarcomas. | RxWiki

Phase II Study of NGR-hTNF in Combination With Doxorubicin in Patients Affected by Soft Tissue Sarcomas.

Overview[ - collapse ][ - ]

Purpose	The main objective of the trial is to document the preliminary antitumor activity of two doses of NGR-hTNF administered either alone or in combination with doxorubicin in locally advanced or metastatic soft-tissue sarcoma (STS) patients untreated or previously treated with one or more prior systemic regimen.
Condition	Locally Advanced or Metastatic Soft Tissue Sarcoma
Intervention	Drug: NGR-hTNF Drug: NGR-hTNF Drug: Doxorubicin
Phase	Phase 2
Sponsor	MolMed S.p.A.
Responsible Party	MolMed S.p.A.
ClinicalTrials.gov Identifier	NCT00484341
First Received	June 7, 2007
Last Updated	January 28, 2013
Last verified	January 2013

Tracking Information[ + expand ][ + ]

First Received Date	June 7, 2007
Last Updated Date	January 28, 2013
Start Date	October 2010
Estimated Primary Completion Date	December 2013
Current Primary 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
Current Secondary Outcome Measures	Safety and Toxicity according to NCI-CTCAE criteria (version 4.02) [Time Frame: during the study] [Designated as safety issue: Yes] Duration of Disease Control [Time Frame: every 6-12 weeks] [Designated as safety issue: Yes]Measured from the date of randomization until disease progression, or death due to any cause 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 Response rate [Time Frame: every 6-12 weeks] [Designated as safety issue: No]Measured both according to RECIST criteria and by FDG-PET Tumor response [Time Frame: every 6-12 weeks] [Designated as safety issue: No]Evaluated by a centralized review of changes in tumor density on CT scan and/or perfusion MRI

Descriptive Information[ + expand ][ + ]

Brief Title	Phase II Study of NGR-hTNF in Combination With Doxorubicin in Patients Affected by Soft Tissue Sarcomas.
Official Title	NGR016: Randomized Phase II Study Evaluating Two Doses of NGR-hTNF Administered Either as Single Agent or in Combination With Doxorubicin in Patients With Advanced Soft Tissue Sarcoma (STS)
Brief Summary	The main objective of the trial is to document the preliminary antitumor activity of two doses of NGR-hTNF administered either alone or in combination with doxorubicin in locally advanced or metastatic soft-tissue sarcoma (STS) patients untreated or previously treated with one or more prior systemic regimen.
Detailed Description	Considering the safety/toxicity profile of NGR-hTNF characterized by mild-to-moderate constitutional symptoms when given either every three weeks or weekly both at low (0.8 µg/m^2) and high dose (45 µg/m^2); the reversibility of these adverse events generally occurring only during the infusion time; the absence of overlapping toxicities with chemotherapeutic agents; and the safety and preliminary antitumor activity observed in phase Ib trial with doxorubicin, seems justified to evaluate in a randomized 4-arm phase II trial the preliminary antitumor activity of two doses of NGR-hTNF (0.8 µg/m^2 and 45 µg/m^2) administered weekly either alone or in combination with a standard dose of doxorubicin (60 mg/m^2 every three weeks).
Study Type	Interventional
Study Phase	Phase 2
Study Design	Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Condition	Locally Advanced or Metastatic Soft Tissue Sarcoma
Intervention	Drug: NGR-hTNF NGR-hTNF: 0.8 mcg/m² as 60-minute intravenous infusion every week until confirmed evidence of disease progression or unacceptable toxicity occurs Drug: NGR-hTNF NGR-hTNF: 45 mcg/m² as 60-minute intravenous infusion every week until confirmed evidence of disease progression or unacceptable toxicity occurs Drug: Doxorubicin Doxorubicin: 60 mg/m² intravenous infusion over 15 minutes (starting 1 hour after the end of NGR-hTNF infusion) on day 1 every 3 weeks for a maximum of 6 cycles or until cumulative dose of 550 mg/m²
Study Arm (s)	Experimental: A: low-dose NGR-hTNF Experimental: B: high-dose NGR-hTNF Experimental: C: low-dose NGR-hTNF + doxorubicin Experimental: D: high-dose NGR-hTNF + doxorubicin

Recruitment Information[ + expand ][ + ]

Recruitment Status	Recruiting
Estimated Enrollment	96
Estimated Completion Date	December 2013
Estimated Primary Completion Date	December 2013
Eligibility Criteria	Inclusion Criteria: - Patients ≥ 18 years - Histologically-proven, locally advanced, or metastatic STS (excluding extraosseus Ewing sarcoma) - Patients not amenable to surgery, radiotherapy, or combined-modality therapy with curative intent - Patients untreated or previously treated with one or more systemic regimen - ECOG Performance status 0-2 (Appendix A) - At least one untreated (not previously irradiated) target lesion that could be measured in one dimension, according to RECIST criteria - A life expectancy of 12 weeks or more - Adequate baseline bone marrow, hepatic and renal function, defined as follows: - Neutrophils > 1.5 x 109/L and platelets > 100 x 109/L - 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 - Creatinine clearance (estimated according to Cockcroft-Gault formula) ≥ 50 ml/min - Patients may have had prior treatment providing the following conditions are met before treatment start: - Surgery and radiation therapy: wash-out period of 14 days - Systemic therapy: wash-out period of 21 days - Patients must give written informed consent Exclusion Criteria: - Patients may not receive any other investigational agents while on study - Patients with myocardial infarction within the last six (6) months, unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, or serious cardiac arrhythmia requiring medication - LVEF < 55% (only for patients candidate for doxorubicin treatment) - Uncontrolled hypertension - Prolonged 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 or contraindications 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 child-bearing potential must provide a negative pregnancy test (serum or urine) within 14 days prior to registration
Gender	Both
Ages	18 Years
Accepts Healthy Volunteers	No
Contacts	Contact: Paolo Giovanni Casali, MD
Location Countries	France, Italy, United Kingdom

Administrative Information[ + expand ][ + ]

NCT Number	NCT00484341
Other Study ID Numbers	NGR016
Has Data Monitoring Committee	No
Information Provided By	MolMed S.p.A.
Study Sponsor	MolMed S.p.A.
Collaborators	Not Provided
Investigators	Study Director: Antonio Lambiase, MD MolMed S.p.A.
Verification Date	January 2013

Locations[ + expand ][ + ]

Centre Leon Berard	Lyon, France, 69373 Contact: Jean-Yves Blay, MD Principal Investigator: Jean-Yves Blay, MD Not yet recruiting
Institut de Cancérologie Gustave Roussy	Villejuif, France, 94805 Contact: Axel Le Cesne, MD Principal Investigator: Axel Le Cesne, MD Recruiting
Istituto Ortopedico Rizzoli	Bologna, Italy, 40136 Contact: Stefano Ferrari, MD Principal Investigator: Stefano Ferrari, MD Recruiting
Fondazione IRCCS Istituto Nazionale dei Tumori di Milano	Milan, Italy, 20133 Contact: Paolo Giovanni Casali, MD Principal Investigator: Paolo Giovanni Casali, MD Recruiting
IRCCS Policlinico S. Matteo	Pavia, Italy, 27100 Contact: Vittorio Perfetti, MD Principal Investigator: Vittorio Perfetti, MD Not yet recruiting
Università Campus Bio-Medico	Rome, Italy, 00128 Contact: Giuseppe Tonini, MD Principal Investigator: Giuseppe Tonini, MD Recruiting
Clatterbridge Centre for Oncology	Bebington, Wirral, United Kingdom, BA11 3 Contact: Nasim Ali, MD Principal Investigator: Nasim Ali, MD Recruiting