NCT00484341

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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
69

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Oct 2010

Longer than P75 for phase_2

Geographic Reach
3 countries

7 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

June 7, 2007

Completed
1 day until next milestone

First Posted

Study publicly available on registry

June 8, 2007

Completed
3.3 years until next milestone

Study Start

First participant enrolled

October 1, 2010

Completed
5.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2016

Completed
Last Updated

August 29, 2018

Status Verified

August 1, 2018

Enrollment Period

5.6 years

First QC Date

June 7, 2007

Last Update Submit

August 27, 2018

Conditions

Metastatic Adult Soft Tissue Sarcoma

Keywords

NGR-hTNFDoxorubicinSoft Tissue Sarcoma

Outcome Measures

Primary Outcomes (1)

  • Progression-Free Survival (PFS)

    Defined as the time from the date of randomization until disease progression, or death

    every 6-12 weeks

Secondary Outcomes (5)

  • Safety and Toxicity according to NCI-CTCAE criteria (version 4.02)

    during the study

  • Duration of Disease Control

    every 6-12 weeks

  • Overall survival (OS)

    every 6-12 weeks

  • Response rate

    every 6-12 weeks

  • Tumor response

    every 6-12 weeks

Study Arms (4)

A: low-dose NGR-hTNF

EXPERIMENTAL

0.8 mcg/m² of NGR-hTNF

Drug: low-dose NGR-hTNF

B: high-dose NGR-hTNF

EXPERIMENTAL

45 mcg/m² of NGR-hTNF

Drug: high-dose NGR-hTNF

C: low-dose NGR-hTNF + doxorubicin

EXPERIMENTAL

0.8 mcg/m² of NGR-hTNF + doxorubicin

Drug: low-dose NGR-hTNFDrug: Doxorubicin

D: high-dose NGR-hTNF + doxorubicin

EXPERIMENTAL

45 mcg/m² of NGR-hTNF + doxorubicin

Drug: high-dose NGR-hTNFDrug: Doxorubicin

Interventions

low-dose NGR-hTNFDRUG

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

Also known as: NGR-hTNF
A: low-dose NGR-hTNFC: low-dose NGR-hTNF + doxorubicin
high-dose NGR-hTNFDRUG

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

Also known as: NGR-hTNF
B: high-dose NGR-hTNFD: high-dose NGR-hTNF + doxorubicin
DoxorubicinDRUG

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

C: low-dose NGR-hTNF + doxorubicinD: high-dose NGR-hTNF + doxorubicin

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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
  • +2 more criteria

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (7)

Centre Leon Berard

Lyon, 69373, France

Location

Institut de Cancérologie Gustave Roussy

Villejuif, 94805, France

Location

Istituto Ortopedico Rizzoli

Bologna, 40136, Italy

Location

Fondazione IRCCS Istituto Nazionale dei Tumori di Milano

Milan, 20133, Italy

Location

IRCCS Policlinico S. Matteo

Pavia, 27100, Italy

Location

Università Campus Bio-Medico

Rome, 00128, Italy

Location

Clatterbridge Centre for Oncology

Bebington, Wirral, BA11 3, United Kingdom

Location

MeSH Terms

Conditions

Sarcoma

Interventions

tumor necrosis factor-alpha, CNGRC fusion protein, humanDoxorubicin

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft TissueNeoplasms by Histologic TypeNeoplasms

Intervention Hierarchy (Ancestors)

DaunorubicinAnthracyclinesNaphthacenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsPolycyclic CompoundsAminoglycosidesGlycosidesCarbohydrates

Study Officials

  • Antonio Lambiase, MD

    AGC Biologics S.p.A.

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 7, 2007

First Posted

June 8, 2007

Study Start

October 1, 2010

Primary Completion

May 1, 2016

Study Completion

May 1, 2016

Last Updated

August 29, 2018

Record last verified: 2018-08

Locations

IT(4)GB(1)FR(2)