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

June 7, 2007
January 28, 2013
October 2010
December 2013   (final data collection date for primary outcome measure)
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
Antitumor activity defined as response rate according to RECIST criteria
Complete list of historical versions of study NCT00484341 on ClinicalTrials.gov Archive Site
  • 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
Progression Free Survival (PFS) Overall survival (OS) Safety
Not Provided
Not Provided
 
Phase II Study of NGR-hTNF in Combination With Doxorubicin in Patients Affected by Soft Tissue Sarcomas.
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)

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.

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).

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Locally Advanced or Metastatic Soft Tissue Sarcoma
  • 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
  • Experimental: A: low-dose NGR-hTNF
    Intervention: Drug: NGR-hTNF
  • Experimental: B: high-dose NGR-hTNF
    Intervention: Drug: NGR-hTNF
  • Experimental: C: low-dose NGR-hTNF + doxorubicin
    Interventions:
    • Drug: NGR-hTNF
    • Drug: Doxorubicin
  • Experimental: D: high-dose NGR-hTNF + doxorubicin
    Interventions:
    • Drug: NGR-hTNF
    • Drug: Doxorubicin
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
96
December 2013
December 2013   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact: Paolo Giovanni Casali, MD 0
France,   Italy,   United Kingdom
 
NCT00484341
NGR016, 2010-018851-88
No
MolMed S.p.A.
MolMed S.p.A.
Not Provided
Study Director: Antonio Lambiase, MD MolMed S.p.A.
MolMed S.p.A.
January 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP