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

This study is currently recruiting participants.
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
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, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Doxorubicin
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 21, 2014