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

NCT ID: NCT00484341

Last Updated: 2018-08-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 69 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-10-31
• Study Completion Date: 2016-05-31

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.

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).

Conditions

Metastatic Adult Soft Tissue Sarcoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

A: low-dose NGR-hTNF

0.8 mcg/m² of NGR-hTNF

Group Type: EXPERIMENTAL

low-dose NGR-hTNF

Intervention Type: DRUG

NGR-hTNF: 0.8 mcg/m² as 60-minutes intravenous infusion every week until confirmed evidence of disease progression or unacceptable toxicity occurs

B: high-dose NGR-hTNF

45 mcg/m² of NGR-hTNF

Group Type: EXPERIMENTAL

high-dose NGR-hTNF

Intervention Type: DRUG

NGR-hTNF: 45 mcg/m² as 60-minutes intravenous infusion every week until confirmed evidence of disease progression or unacceptable toxicity occurs

C: low-dose NGR-hTNF + doxorubicin

0.8 mcg/m² of NGR-hTNF + doxorubicin

Group Type: EXPERIMENTAL

low-dose NGR-hTNF

Intervention Type: DRUG

NGR-hTNF: 0.8 mcg/m² as 60-minutes intravenous infusion every week until confirmed evidence of disease progression or unacceptable toxicity occurs

Doxorubicin

Intervention Type: DRUG

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

D: high-dose NGR-hTNF + doxorubicin

45 mcg/m² of NGR-hTNF + doxorubicin

Group Type: EXPERIMENTAL

high-dose NGR-hTNF

Intervention Type: DRUG

NGR-hTNF: 45 mcg/m² as 60-minutes intravenous infusion every week until confirmed evidence of disease progression or unacceptable toxicity occurs

Doxorubicin

Intervention Type: DRUG

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

Interventions

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

Intervention Type: 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

Intervention Type: 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

Intervention Type: DRUG

Other Intervention Names

NGR-hTNF; NGR-hTNF

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AGC Biologics S.p.A.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Antonio Lambiase, MD

Role: STUDY_DIRECTOR

AGC Biologics S.p.A.

Locations

Centre Leon Berard

Lyon, , France

Institut de Cancérologie Gustave Roussy

Villejuif, , France

Istituto Ortopedico Rizzoli

Bologna, , Italy

Fondazione IRCCS Istituto Nazionale dei Tumori di Milano

Milan, , Italy

IRCCS Policlinico S. Matteo

Pavia, , Italy

Università Campus Bio-Medico

Rome, , Italy

Clatterbridge Centre for Oncology

Bebington, Wirral, United Kingdom

Countries

France; Italy; United Kingdom

Other Identifiers

2010-018851-88

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

NGR016

Identifier Type: -

Identifier Source: org_study_id