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:
MolMed S.p.A.
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
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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 May 23, 2013