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

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ClinicalTrials.gov Identifier: NCT00484341
Recruitment Status : Completed
First Posted : June 8, 2007
Last Update Posted : August 29, 2018
Sponsor:
Information provided by (Responsible Party):
MolMed S.p.A.

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.

Condition or disease Intervention/treatment Phase
Metastatic Adult Soft Tissue Sarcoma Drug: low-dose NGR-hTNF Drug: high-dose NGR-hTNF Drug: Doxorubicin Phase 2

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  (Clinical Trial)
Actual Enrollment : 69 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (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)
Actual Study Start Date : October 2010
Actual Primary Completion Date : May 2016
Actual Study Completion Date : May 2016


Arm Intervention/treatment
Experimental: A: low-dose NGR-hTNF
0.8 mcg/m² of NGR-hTNF
Drug: low-dose NGR-hTNF
NGR-hTNF: 0.8 mcg/m² as 60-minutes intravenous infusion every week until confirmed evidence of disease progression or unacceptable toxicity occurs
Other Name: NGR-hTNF

Experimental: B: high-dose NGR-hTNF
45 mcg/m² of NGR-hTNF
Drug: high-dose NGR-hTNF
NGR-hTNF: 45 mcg/m² as 60-minutes intravenous infusion every week until confirmed evidence of disease progression or unacceptable toxicity occurs
Other Name: NGR-hTNF

Experimental: C: low-dose NGR-hTNF + doxorubicin
0.8 mcg/m² of NGR-hTNF + doxorubicin
Drug: low-dose NGR-hTNF
NGR-hTNF: 0.8 mcg/m² as 60-minutes intravenous infusion every week until confirmed evidence of disease progression or unacceptable toxicity occurs
Other Name: NGR-hTNF

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
45 mcg/m² of NGR-hTNF + doxorubicin
Drug: high-dose NGR-hTNF
NGR-hTNF: 45 mcg/m² as 60-minutes intravenous infusion every week until confirmed evidence of disease progression or unacceptable toxicity occurs
Other Name: NGR-hTNF

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




Primary Outcome Measures :
  1. Progression-Free Survival (PFS) [ Time Frame: every 6-12 weeks ]
    Defined as the time from the date of randomization until disease progression, or death


Secondary Outcome Measures :
  1. Safety and Toxicity according to NCI-CTCAE criteria (version 4.02) [ Time Frame: during the study ]
    To evaluate safety and toxicity profile related to NGR-hTNF

  2. Duration of Disease Control [ Time Frame: every 6-12 weeks ]
    Measured from the date of randomization until disease progression, or death due to any cause

  3. Overall survival (OS) [ Time Frame: every 6-12 weeks ]
    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

  4. Response rate [ Time Frame: every 6-12 weeks ]
    Measured both according to RECIST criteria and by FDG-PET

  5. Tumor response [ Time Frame: every 6-12 weeks ]
    Evaluated by a centralized review of changes in tumor density on CT scan and/or perfusion MRI



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00484341


Locations
France
Centre Leon Berard
Lyon, France, 69373
Institut de Cancérologie Gustave Roussy
Villejuif, France, 94805
Italy
Istituto Ortopedico Rizzoli
Bologna, Italy, 40136
Fondazione IRCCS Istituto Nazionale dei Tumori di Milano
Milan, Italy, 20133
IRCCS Policlinico S. Matteo
Pavia, Italy, 27100
Università Campus Bio-Medico
Rome, Italy, 00128
United Kingdom
Clatterbridge Centre for Oncology
Bebington, Wirral, United Kingdom, BA11 3
Sponsors and Collaborators
MolMed S.p.A.
Investigators
Study Director: Antonio Lambiase, MD MolMed S.p.A.

Responsible Party: MolMed S.p.A.
ClinicalTrials.gov Identifier: NCT00484341     History of Changes
Other Study ID Numbers: NGR016
2010-018851-88 ( EudraCT Number )
First Posted: June 8, 2007    Key Record Dates
Last Update Posted: August 29, 2018
Last Verified: August 2018

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
Liposomal doxorubicin
Antibiotics, Antineoplastic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action