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

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2013 by MolMed S.p.A.
Sponsor:
Information provided by (Responsible Party):
MolMed S.p.A.
ClinicalTrials.gov Identifier:
NCT00484341
First received: June 7, 2007
Last updated: January 28, 2013
Last verified: January 2013
  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 Intervention Phase
Locally Advanced or Metastatic Soft Tissue Sarcoma
Drug: NGR-hTNF
Drug: Doxorubicin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


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

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


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


Estimated Enrollment: 96
Study Start Date: October 2010
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A: low-dose NGR-hTNF 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
Experimental: B: high-dose NGR-hTNF 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
Experimental: C: low-dose NGR-hTNF + doxorubicin 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: 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
Experimental: D: high-dose NGR-hTNF + doxorubicin 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

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).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00484341

Contacts
Contact: Paolo Giovanni Casali, MD 0

Locations
France
Centre Leon Berard Not yet recruiting
Lyon, France, 69373
Contact: Jean-Yves Blay, MD         
Principal Investigator: Jean-Yves Blay, MD         
Institut de Cancérologie Gustave Roussy Recruiting
Villejuif, France, 94805
Contact: Axel Le Cesne, MD         
Principal Investigator: Axel Le Cesne, MD         
Italy
Istituto Ortopedico Rizzoli Recruiting
Bologna, Italy, 40136
Contact: Stefano Ferrari, MD         
Principal Investigator: Stefano Ferrari, MD         
Fondazione IRCCS Istituto Nazionale dei Tumori di Milano Recruiting
Milan, Italy, 20133
Contact: Paolo Giovanni Casali, MD         
Principal Investigator: Paolo Giovanni Casali, MD         
Sub-Investigator: Elena Palassini, MD         
IRCCS Policlinico S. Matteo Not yet recruiting
Pavia, Italy, 27100
Contact: Vittorio Perfetti, MD         
Principal Investigator: Vittorio Perfetti, MD         
Università Campus Bio-Medico Recruiting
Rome, Italy, 00128
Contact: Giuseppe Tonini, MD         
Principal Investigator: Giuseppe Tonini, MD         
United Kingdom
Clatterbridge Centre for Oncology Recruiting
Bebington, Wirral, United Kingdom, BA11 3
Contact: Nasim Ali, MD         
Principal Investigator: Nasim Ali, 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: NCT00484341     History of Changes
Other Study ID Numbers: NGR016, 2010-018851-88
Study First Received: June 7, 2007
Last Updated: January 28, 2013
Health Authority: Italy: Ethics Committee
United Kingdom: Medicines and Healthcare Products Regulatory Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by MolMed S.p.A.:
NGR-hTNF
Doxorubicin
Soft Tissue Sarcoma

Additional relevant MeSH terms:
Sarcoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Connective and Soft Tissue
Doxorubicin
Liposomal doxorubicin
Antibiotics, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses
Topoisomerase II Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on October 20, 2014