- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00484341
Phase II Study of NGR-hTNF in Combination With Doxorubicin in Patients Affected by Soft Tissue Sarcomas.
August 27, 2018 updated by: AGC Biologics S.p.A.
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
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
Enrollment (Actual)
69
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Lyon, France, 69373
- Centre Léon Bérard
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Villejuif, France, 94805
- Institut de Cancerologie Gustave Roussy
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Bologna, Italy, 40136
- Istituto Ortopedico Rizzoli
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Milan, Italy, 20133
- Fondazione IRCCS Istituto Nazionale dei Tumori di Milano
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Pavia, Italy, 27100
- IRCCS Policlinico S. Matteo
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Rome, Italy, 00128
- Università Campus Bio-Medico
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Wirral
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Bebington, Wirral, United Kingdom, BA11 3
- Clatterbridge Centre for Oncology
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: A: low-dose NGR-hTNF
0.8 mcg/m² of NGR-hTNF
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NGR-hTNF: 0.8 mcg/m² as 60-minutes intravenous infusion every week until confirmed evidence of disease progression or unacceptable toxicity occurs
Other Names:
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Experimental: B: high-dose NGR-hTNF
45 mcg/m² of NGR-hTNF
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NGR-hTNF: 45 mcg/m² as 60-minutes intravenous infusion every week until confirmed evidence of disease progression or unacceptable toxicity occurs
Other Names:
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Experimental: C: low-dose NGR-hTNF + doxorubicin
0.8 mcg/m² of NGR-hTNF + doxorubicin
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NGR-hTNF: 0.8 mcg/m² as 60-minutes intravenous infusion every week until confirmed evidence of disease progression or unacceptable toxicity occurs
Other Names:
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
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Experimental: D: high-dose NGR-hTNF + doxorubicin
45 mcg/m² of NGR-hTNF + doxorubicin
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NGR-hTNF: 45 mcg/m² as 60-minutes intravenous infusion every week until confirmed evidence of disease progression or unacceptable toxicity occurs
Other Names:
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
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Progression-Free Survival (PFS)
Time Frame: every 6-12 weeks
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Defined as the time from the date of randomization until disease progression, or death
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every 6-12 weeks
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall survival (OS)
Time Frame: every 6-12 weeks
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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
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every 6-12 weeks
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Safety and Toxicity according to NCI-CTCAE criteria (version 4.02)
Time Frame: during the study
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To evaluate safety and toxicity profile related to NGR-hTNF
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during the study
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Duration of Disease Control
Time Frame: every 6-12 weeks
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Measured from the date of randomization until disease progression, or death due to any cause
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every 6-12 weeks
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Response rate
Time Frame: every 6-12 weeks
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Measured both according to RECIST criteria and by FDG-PET
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every 6-12 weeks
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Tumor response
Time Frame: every 6-12 weeks
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Evaluated by a centralized review of changes in tumor density on CT scan and/or perfusion MRI
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every 6-12 weeks
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
October 1, 2010
Primary Completion (Actual)
May 1, 2016
Study Completion (Actual)
May 1, 2016
Study Registration Dates
First Submitted
June 7, 2007
First Submitted That Met QC Criteria
June 7, 2007
First Posted (Estimate)
June 8, 2007
Study Record Updates
Last Update Posted (Actual)
August 29, 2018
Last Update Submitted That Met QC Criteria
August 27, 2018
Last Verified
August 1, 2018
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- NGR016
- 2010-018851-88 (EudraCT Number)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Metastatic Adult Soft Tissue Sarcoma
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AIO-Studien-gGmbHAstraZenecaCompletedRecurrent Adult Soft Tissue Sarcoma | Metastatic Adult Soft Tissue SarcomaGermany
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University Medicine GreifswaldBristol-Myers Squibb; Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus... and other collaboratorsCompletedMetastatic Adult Soft Tissue SarcomaGermany
-
OHSU Knight Cancer InstituteNational Cancer Institute (NCI)WithdrawnStage III Adult Soft Tissue Sarcoma | Stage IV Adult Soft Tissue Sarcoma | Stage II Adult Soft Tissue Sarcoma | Stage IIA Adult Soft Tissue Sarcoma | Stage IIB Adult Soft Tissue Sarcoma | Stage IIC Adult Soft Tissue Sarcoma
-
National Institutes of Health Clinical Center (CC)CompletedRecurrent Adult Soft Tissue Sarcoma | Stage III Adult Soft Tissue Sarcoma | Stage IVA Adult Soft Tissue Sarcoma | Stage IIB Adult Soft Tissue Sarcoma | Stage IIC Adult Soft Tissue Sarcoma | Stage IVB Adult Soft Tissue Sarcoma
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National Cancer Institute (NCI)TerminatedRecurrent Adult Soft Tissue Sarcoma | Stage III Adult Soft Tissue Sarcoma | Stage IV Adult Soft Tissue Sarcoma | Stage I Adult Soft Tissue Sarcoma | Stage II Adult Soft Tissue SarcomaUnited States
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-
Radiation Therapy Oncology GroupNational Cancer Institute (NCI)WithdrawnRecurrent Adult Soft Tissue Sarcoma | Stage III Adult Soft Tissue Sarcoma | Stage IVA Adult Soft Tissue Sarcoma | Stage IIB Adult Soft Tissue Sarcoma | Stage IIC Adult Soft Tissue SarcomaUnited States, Canada
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University of WashingtonNational Cancer Institute (NCI)CompletedStage III Adult Soft Tissue Sarcoma | Stage IV Adult Soft Tissue Sarcoma | Stage IIA Adult Soft Tissue SarcomaUnited States
-
Northwestern UniversityNational Cancer Institute (NCI); GlaxoSmithKlineCompletedRecurrent Osteosarcoma | Metastatic Osteosarcoma | Recurrent Adult Soft Tissue Sarcoma | Stage IV Adult Soft Tissue Sarcoma | Adult Liposarcoma | Metastatic Liposarcoma | Recurrent LiposarcomaUnited States
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National Cancer Institute (NCI)Radiation Therapy Oncology GroupTerminatedRecurrent Adult Soft Tissue Sarcoma | Stage I Adult Soft Tissue Sarcoma AJCC v7 | Stage II Adult Soft Tissue Sarcoma AJCC v7 | Stage III Adult Soft Tissue Sarcoma AJCC v7United States
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