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Phase II Study of NGR-hTNF in Combination With Doxorubicin in Platinum-resistant Ovarian Cancer (NGR018)

Primary Purpose

Ovarian Cancer

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
NGR-hTNF
Pegylated liposomal doxorubicin
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 Ovarian Cancer focused on measuring NGR-hTNF, Pegylated liposomal doxorubicin, Doxorubicin, Platinum-resistant, Progression or recurrence Ovarian Cancer, Ovarian Cancer, Advanced or metastatic

Eligibility Criteria

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

Inclusion Criteria:

  • Age ≥ 18 years
  • Histologically-proven ovarian cancer, fallopian tube and primary peritoneal cancer in advanced or metastatic stage
  • Patients previously treated with a maximum of two platinum-based regimen plus paclitaxel and with documented progressive disease on treatment (refractory patient population) or within 6 months from last chemotherapy cycle (resistant patient population)
  • ECOG Performance status 0 - 2
  • Life expectancy of 12 weeks or more
  • Normal cardiac function

  • Adequate baseline bone marrow, hepatic and renal function defined as follows:

    1. Neutrophils ≥ 1.5 x 109/L; platelets ≥ 100 x 109/L; hemoglobin ≥ 9 g/dL
    2. Bilirubin ≤ 1.5 x ULN
    3. AST and/or ALT ≤ 2.5 x ULN in absence of liver metastasis or ≤ 5 x ULN in presence of liver metastasis
    4. Serum creatinine < 1.5 x ULN
  • At least one (not previously irradiated) target lesion or non-measurable disease only, according to RECIST criteria

  • Patients may have had prior therapy providing the following conditions are met:

    • Surgery and radiation therapy: wash-out period of 14 days
    • Systemic anti-tumor therapy: wash-out period of 21 days
  • Patients must give written informed consent to participate in the study

Exclusion Criteria:

  • Patients must not receive any other investigational agents while on study
  • More than two previous chemotherapy lines and previous treatment with anthracycline
  • Patients with myocardial infarction within the last six months, unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, or serious cardiac arrhythmia requiring medication
  • Prolonged QTc interval (congenital or acquired) > 450 ms
  • History or evidence upon physical examination of CNS disease unless adequately treated
  • 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 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.

Sites / Locations

  • Ospedale San Raffaele
  • Fondazione IRCCS Istituto Nazionale dei Tumori
  • Istituto Europeo di Oncologia
  • Istituto Nazionale Tumori IRCCS Fondazione "Giovanni Pascale"
  • Ospedale S. Maria della Misericordia
  • Policlinico Universitario "Agostino Gemelli"
  • Beatson Oncology Centre, Gartnavel Hospital
  • Clatterbridge Centre for Oncology

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Arm A: NGR-hTNF+ anthracycline

Arm B: anthracycline

Arm Description

NGR-hTNF+Pegylated Liposomal Doxorubicin or Doxorubicin

Pegylated Liposomal Doxorubicin or 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

Overall survival (OS)
defined as the time from the date of randomization until death due to any cause.
Response Rate (RR)
defined as the percentage of patients who have a best-response rating of complete or partial response, according to standard RECIST criteria.
Disease Control Rate (DCR)
defined as the percentage of patients who have a best-response rating of complete response, partial response, or stable disease, according to standard RECIST criteria.
Duration of Disease Control
measured from the date of randomization until disease progression, or death due to any cause.
Safety and Toxicity according to NCI-CTCAE criteria (version 4.03)
To evaluate safety and toxicity profile related to NGR-hTNF

Full Information

First Posted
May 19, 2011
Last Updated
September 25, 2018
Sponsor
AGC Biologics S.p.A.
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1. Study Identification

Unique Protocol Identification Number
NCT01358071
Brief Title
Phase II Study of NGR-hTNF in Combination With Doxorubicin in Platinum-resistant Ovarian Cancer
Acronym
NGR018
Official Title
NGR018: Randomized Phase II Study of NGR-hTNF Plus an Anthracycline Versus an Anthracycline Alone in Platinum-resistant Ovarian Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
September 2018
Overall Recruitment Status
Completed
Study Start Date
June 2011 (Actual)
Primary Completion Date
December 2016 (Actual)
Study Completion Date
December 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 primary objective of this randomized phase II trial is to compare progression-free survival (PFS) in patients randomized to NGR-hTNF plus an anthracycline versus patients randomized to an anthracycline alone
Detailed Description
Considering the safety/toxicity profile of NGR-hTNF characterized by mild-to-moderate constitutional symptoms, the reversibility of these adverse events generally occurring only during the infusion time; the absence of overlapping toxicities with chemotherapeutic agents; the safety and preliminary antitumor activity observed in previous trial with doxorubicin; and the objective response rate (RR) registered in a phase II trial in previously treated ovarian cancer patients seems justified to evaluate in a randomized phase II trial the efficacy of NGR-hTNF against a doxorubicin-based option in advanced ovarian cancer patients progressing or recurrent after a standard platinum/taxane-based chemotherapy.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ovarian Cancer
Keywords
NGR-hTNF, Pegylated liposomal doxorubicin, Doxorubicin, Platinum-resistant, Progression or recurrence Ovarian Cancer, Ovarian Cancer, Advanced or metastatic

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
Arm A: NGR-hTNF+ anthracycline
Arm Type
Experimental
Arm Description
NGR-hTNF+Pegylated Liposomal Doxorubicin or Doxorubicin
Arm Title
Arm B: anthracycline
Arm Type
Active Comparator
Arm Description
Pegylated Liposomal Doxorubicin or Doxorubicin
Intervention Type
Drug
Intervention Name(s)
NGR-hTNF
Intervention Description
NGR-hTNF: 0.8 mcg/m² as 60 minutes intravenous infusion weekly or every 3 or 4 weeks until confirmed evidence of disease progression or unacceptable toxicity occurs
Intervention Type
Drug
Intervention Name(s)
Pegylated liposomal doxorubicin
Intervention Description
50 mg/m² iv every 4 weeks until confirmed evidence of disease progression
Intervention Type
Drug
Intervention Name(s)
Doxorubicin
Intervention Description
60 mg/m² iv every 3 weeks for a maximum of 8 cycles
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
from the date of randomization, every 6 and 8 weeks based on type of chemotherapy during treatment and every 12 weeks during the follow-up until PD or death
Secondary Outcome Measure Information:
Title
Overall survival (OS)
Description
defined as the time from the date of randomization until death due to any cause.
Time Frame
from the date of randomization, every 6 and 8 weeks based on type of chemotherapy during treatment and every 12 weeks during follow-up until death
Title
Response Rate (RR)
Description
defined as the percentage of patients who have a best-response rating of complete or partial response, according to standard RECIST criteria.
Time Frame
from the date of randomization, every 6 and 8 weeks based on type of chemotherapy during treatment and every 12 weeks during the follow-up until PD or death
Title
Disease Control Rate (DCR)
Description
defined as the percentage of patients who have a best-response rating of complete response, partial response, or stable disease, according to standard RECIST criteria.
Time Frame
from the date of randomization, every 6 and 8 weeks based on type of chemotherapy during treatment and every 12 weeks during the follow-up until PD or death
Title
Duration of Disease Control
Description
measured from the date of randomization until disease progression, or death due to any cause.
Time Frame
from the date of randomization, every 6 and 8 weeks based on type of chemotherapy during treatment and every 12 weeks during the follow-up until PD or death
Title
Safety and Toxicity according to NCI-CTCAE criteria (version 4.03)
Description
To evaluate safety and toxicity profile related to NGR-hTNF
Time Frame
from the start of treatment until 28 days after last treatment

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age ≥ 18 years Histologically-proven ovarian cancer, fallopian tube and primary peritoneal cancer in advanced or metastatic stage Patients previously treated with a maximum of two platinum-based regimen plus paclitaxel and with documented progressive disease on treatment (refractory patient population) or within 6 months from last chemotherapy cycle (resistant patient population) ECOG Performance status 0 - 2 Life expectancy of 12 weeks or more Normal cardiac function Adequate baseline bone marrow, hepatic and renal function defined as follows: Neutrophils ≥ 1.5 x 109/L; platelets ≥ 100 x 109/L; hemoglobin ≥ 9 g/dL 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 At least one (not previously irradiated) target lesion or non-measurable disease only, according to RECIST criteria Patients may have had prior therapy providing the following conditions are met: Surgery and radiation therapy: wash-out period of 14 days Systemic anti-tumor therapy: wash-out period of 21 days Patients must give written informed consent to participate in the study Exclusion Criteria: Patients must not receive any other investigational agents while on study More than two previous chemotherapy lines and previous treatment with anthracycline Patients with myocardial infarction within the last six months, unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, or serious cardiac arrhythmia requiring medication Prolonged QTc interval (congenital or acquired) > 450 ms History or evidence upon physical examination of CNS disease unless adequately treated 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 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.
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
Ospedale San Raffaele
City
Milan
ZIP/Postal Code
20132
Country
Italy
Facility Name
Fondazione IRCCS Istituto Nazionale dei Tumori
City
Milan
ZIP/Postal Code
20133
Country
Italy
Facility Name
Istituto Europeo di Oncologia
City
Milan
ZIP/Postal Code
20141
Country
Italy
Facility Name
Istituto Nazionale Tumori IRCCS Fondazione "Giovanni Pascale"
City
Naples
ZIP/Postal Code
80131
Country
Italy
Facility Name
Ospedale S. Maria della Misericordia
City
Perugia
ZIP/Postal Code
06156
Country
Italy
Facility Name
Policlinico Universitario "Agostino Gemelli"
City
Rome
ZIP/Postal Code
00168
Country
Italy
Facility Name
Beatson Oncology Centre, Gartnavel Hospital
City
Glasgow
State/Province
Scotland
ZIP/Postal Code
G12 0YN
Country
United Kingdom
Facility Name
Clatterbridge Centre for Oncology
City
Bebington
State/Province
Wirral
ZIP/Postal Code
CH63 4JY
Country
United Kingdom

12. IPD Sharing Statement

Learn more about this trial

Phase II Study of NGR-hTNF in Combination With Doxorubicin in Platinum-resistant Ovarian Cancer

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