NGR-hTNF in Combination With an Anthracycline in Platinum-resistant Ovarian Cancer (NGR018)

January 14, 2019 updated by: AGC Biologics S.p.A.

NGR018: Randomized Phase II Study of NGR-hTNF Plus an Anthracycline Versus an Anthracycline Alone in Platinum-resistant Ovarian Cancer

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Study Type

Interventional

Enrollment (Actual)

14

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Milan, Italy, 20132
        • Ospedale San Raffaele
      • Milan, Italy, 20133
        • Fondazione IRCCS Istituto Nazionale dei Tumori
      • Milan, Italy, 20141
        • Istituto Europeo di Oncologia
      • Naples, Italy, 80131
        • Istituto Nazionale Tumori IRCCS Fondazione "Giovanni Pascale"

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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:

    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:

    1. Surgery and radiation therapy: wash-out period of 14 days
    2. 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm A: NGR-hTNF+ anthracycline
NGR-hTNF+Pegylated Liposomal Doxorubicin or Doxorubicin
Drug: Pegylated liposomal doxorubicin
50 mg/m² iv every 4 weeks until confirmed evidence of disease progression
Drug: Doxorubicin
60 mg/m² iv every 3 weeks for a maximum of 8 cycles
Drug: 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
Active Comparator: Arm B: anthracycline
Pegylated Liposomal Doxorubicin or Doxorubicin
Drug: Pegylated liposomal doxorubicin
50 mg/m² iv every 4 weeks until confirmed evidence of disease progression
Drug: Doxorubicin
60 mg/m² iv every 3 weeks for a maximum of 8 cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety according to NCI-CTCAE criteria (version 4.03)
Time Frame: from the start of treatment until 28 days after last treatment
To evaluate safety profile related to NGR-hTNF
from the start of treatment until 28 days after last treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-Free Survival (PFS)
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
Defined as the time from the date of randomization until disease progression, or death
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
Overall survival (OS)
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
defined as the time from the date of randomization until death due to any cause
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
Response Rate (RR)
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
defined as the percentage of patients who have a best-response rating of complete or partial response, according to standard RECIST criteria
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
Disease Control Rate (DCR)
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
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
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
Duration of Disease Control
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
measured from the date of randomization until disease progression, or death due to any cause
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

AGC Biologics S.p.A.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 1, 2013

Primary Completion (Actual)

December 1, 2016

Study Completion (Actual)

December 1, 2016

Study Registration Dates

First Submitted

October 3, 2018

First Submitted That Met QC Criteria

January 14, 2019

First Posted (Actual)

January 15, 2019

Study Record Updates

Last Update Posted (Actual)

January 15, 2019

Last Update Submitted That Met QC Criteria

January 14, 2019

Last Verified

January 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NGR018-IPR/26
  • 2012-005745-20 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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