Back to resultsNGR-hTNF in Combination With an Anthracycline in Platinum-resistant Ovarian Cancer (NGR018)
Primary Purpose
Ovarian Cancer
Status
Completed
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
NGR-hTNF
Pegylated liposomal doxorubicin
Doxorubicin
Sponsored by
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
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 and absence of uncontrolled hypertension
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 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
Sites / Locations
- Ospedale San Raffaele
- Fondazione IRCCS Istituto Nazionale dei Tumori
- Istituto Europeo di Oncologia
- Istituto Nazionale Tumori IRCCS Fondazione "Giovanni Pascale"
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
Safety according to NCI-CTCAE criteria (version 4.03)
To evaluate safety profile related to NGR-hTNF
Secondary Outcome Measures
Progression-Free Survival (PFS)
Defined as the time from the date of randomization until disease progression, or death
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
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03804866
Brief Title
NGR-hTNF in Combination With an Anthracycline in Platinum-resistant Ovarian Cancer (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
January 2019
Overall Recruitment Status
Completed
Study Start Date
March 2013 (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 extension protocol is to evaluate the early safety of a new schedule of NGR-hTNF given weekly, instead of every 3 or 4 weeks, in a cohort of 12 patients randomized to the experimental arm A, as compared to a reference cohort of 12 patients randomized to an anthracycline alone
Detailed Description
In this extension protocol IPR/26 of completed IPR/24 study, considering the relatively short half-life of approximately 1 hour and the favourable toxicity profile of NGR-hTNF, characterized by transient constitutional symptoms occurring during the first day of administration, an additional cohort of 24 patients will be randomized and the 12 patients enrolled in arm A will receive the same dose of NGR-hTNF 0.8 mcg/m2 given as 60 minutes infusion every week. the weekly schedule of NGR-hTNF 0.8 mcg/m2 has previously been tested in several studies
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
14 (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 every week 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
Safety according to NCI-CTCAE criteria (version 4.03)
Description
To evaluate safety profile related to NGR-hTNF
Time Frame
from the start of treatment until 28 days after last treatment
Secondary 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 randomization date, every 6-8 weeks based on chemotherapy during treatment and every 12 weeks during follow-up until first documented PD or death from any cause, whichever came first, assessed up through study completion, approximately 12 months
Title
Overall survival (OS)
Description
defined as the time from the date of randomization until death due to any cause
Time Frame
from randomization date, every 6-8 weeks based on type of chemotherapy during treatment and every 12 weeks during follow-up until date of death, from any cause, assessed up through study completion, approximately 12 months
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 randomization date, every 6-8 weeks based on chemotherapy during treatment and every 12 weeks during follow-up until first documented PD or death from any cause, whichever came first, assessed up through study completion, approximately 12 months
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 randomization date, every 6-8 weeks based on chemotherapy during treatment and every 12 weeks during follow-up until first documented PD or death from any cause, whichever came first, assessed up through study completion, approximately 12 months
Title
Duration of Disease Control
Description
measured from the date of randomization until disease progression, or death due to any cause
Time Frame
from randomization date, every 6-8 weeks based on chemotherapy during treatment and every 12 weeks during follow-up until first documented PD or death from any cause, whichever came first, assessed up through study completion, approximately 12 months
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 and absence of uncontrolled hypertension
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 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
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
12. IPD Sharing Statement
Learn more about this trial
NGR-hTNF in Combination With an Anthracycline in Platinum-resistant Ovarian Cancer (NGR018)
We'll reach out to this number within 24 hrs