search
Back to results

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

Primary Purpose

Metastatic Adult Soft Tissue Sarcoma

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
low-dose NGR-hTNF
high-dose NGR-hTNF
Doxorubicin
Sponsored by
AGC Biologics S.p.A.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Adult Soft Tissue Sarcoma focused on measuring NGR-hTNF, Doxorubicin, Soft Tissue Sarcoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Centre Leon Berard
  • Institut de Cancérologie Gustave Roussy
  • Istituto Ortopedico Rizzoli
  • Fondazione IRCCS Istituto Nazionale dei Tumori di Milano
  • IRCCS Policlinico S. Matteo
  • Università Campus Bio-Medico
  • Clatterbridge Centre for Oncology

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

A: low-dose NGR-hTNF

B: high-dose NGR-hTNF

C: low-dose NGR-hTNF + doxorubicin

D: high-dose NGR-hTNF + doxorubicin

Arm Description

0.8 mcg/m² of NGR-hTNF

45 mcg/m² of NGR-hTNF

0.8 mcg/m² of NGR-hTNF + doxorubicin

45 mcg/m² of NGR-hTNF + doxorubicin

Outcomes

Primary Outcome Measures

Progression-Free Survival (PFS)
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)
To evaluate safety and toxicity profile related to NGR-hTNF
Duration of Disease Control
Measured from the date of randomization until disease progression, or death due to any cause
Overall survival (OS)
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
Measured both according to RECIST criteria and by FDG-PET
Tumor response
Evaluated by a centralized review of changes in tumor density on CT scan and/or perfusion MRI

Full Information

First Posted
June 7, 2007
Last Updated
August 27, 2018
Sponsor
AGC Biologics S.p.A.
search

1. Study Identification

Unique Protocol Identification Number
NCT00484341
Brief Title
Phase II Study of NGR-hTNF in Combination With Doxorubicin in Patients Affected by Soft Tissue Sarcomas.
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)
Study Type
Interventional

2. Study Status

Record Verification Date
August 2018
Overall Recruitment Status
Completed
Study Start Date
October 2010 (Actual)
Primary Completion Date
May 2016 (Actual)
Study Completion Date
May 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AGC Biologics S.p.A.

4. Oversight

Data Monitoring Committee
No

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Adult Soft Tissue Sarcoma
Keywords
NGR-hTNF, Doxorubicin, Soft Tissue Sarcoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
69 (Actual)

8. Arms, Groups, and Interventions

Arm Title
A: low-dose NGR-hTNF
Arm Type
Experimental
Arm Description
0.8 mcg/m² of NGR-hTNF
Arm Title
B: high-dose NGR-hTNF
Arm Type
Experimental
Arm Description
45 mcg/m² of NGR-hTNF
Arm Title
C: low-dose NGR-hTNF + doxorubicin
Arm Type
Experimental
Arm Description
0.8 mcg/m² of NGR-hTNF + doxorubicin
Arm Title
D: high-dose NGR-hTNF + doxorubicin
Arm Type
Experimental
Arm Description
45 mcg/m² of NGR-hTNF + doxorubicin
Intervention Type
Drug
Intervention Name(s)
low-dose NGR-hTNF
Other Intervention Name(s)
NGR-hTNF
Intervention Description
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
Intervention Name(s)
high-dose NGR-hTNF
Other Intervention Name(s)
NGR-hTNF
Intervention Description
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
Intervention Name(s)
Doxorubicin
Intervention Description
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 Measure Information:
Title
Progression-Free Survival (PFS)
Description
Defined as the time from the date of randomization until disease progression, or death
Time Frame
every 6-12 weeks
Secondary Outcome Measure Information:
Title
Safety and Toxicity according to NCI-CTCAE criteria (version 4.02)
Description
To evaluate safety and toxicity profile related to NGR-hTNF
Time Frame
during the study
Title
Duration of Disease Control
Description
Measured from the date of randomization until disease progression, or death due to any cause
Time Frame
every 6-12 weeks
Title
Overall survival (OS)
Description
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
Time Frame
every 6-12 weeks
Title
Response rate
Description
Measured both according to RECIST criteria and by FDG-PET
Time Frame
every 6-12 weeks
Title
Tumor response
Description
Evaluated by a centralized review of changes in tumor density on CT scan and/or perfusion MRI
Time Frame
every 6-12 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Antonio Lambiase, MD
Organizational Affiliation
AGC Biologics S.p.A.
Official's Role
Study Director
Facility Information:
Facility Name
Centre Leon Berard
City
Lyon
ZIP/Postal Code
69373
Country
France
Facility Name
Institut de Cancérologie Gustave Roussy
City
Villejuif
ZIP/Postal Code
94805
Country
France
Facility Name
Istituto Ortopedico Rizzoli
City
Bologna
ZIP/Postal Code
40136
Country
Italy
Facility Name
Fondazione IRCCS Istituto Nazionale dei Tumori di Milano
City
Milan
ZIP/Postal Code
20133
Country
Italy
Facility Name
IRCCS Policlinico S. Matteo
City
Pavia
ZIP/Postal Code
27100
Country
Italy
Facility Name
Università Campus Bio-Medico
City
Rome
ZIP/Postal Code
00128
Country
Italy
Facility Name
Clatterbridge Centre for Oncology
City
Bebington
State/Province
Wirral
ZIP/Postal Code
BA11 3
Country
United Kingdom

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs