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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01358071
Recruitment Status : Unknown
Verified October 2015 by MolMed S.p.A..
Recruitment status was:  Active, not recruiting
First Posted : May 23, 2011
Last Update Posted : October 9, 2015
Information provided by (Responsible Party):
MolMed S.p.A.

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

Condition or disease Intervention/treatment Phase
Ovarian Cancer Drug: NGR-hTNF Drug: Pegylated liposomal doxorubicin Drug: Doxorubicin Phase 2

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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 124 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: NGR018: Randomized Phase II Study of NGR-hTNF Plus an Anthracycline Versus an Anthracycline Alone in Platinum-resistant Ovarian Cancer
Study Start Date : June 2011
Estimated Primary Completion Date : June 2016
Estimated Study Completion Date : June 2017

Arm Intervention/treatment
Experimental: Arm A: NGR-hTNF+ anthracycline
NGR-hTNF+Pegylated Liposomal Doxorubicin or Doxorubicin
Drug: NGR-hTNF
NGR-hTNF: 0.8 mcg/m² as 60-minute intravenous infusion weekly or every 3 or 4 weeks until confirmed evidence of disease progression or unacceptable toxicity occurs
Drug: Pegylated liposomal doxorubicin
50 mg/m² iv every 4 weeks until confirmed evidence of disease progression
Drug: Doxorubicin
60 mg/m^2 iv every 3 weeks for a maximum of 8 cycles
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/m^2 iv every 3 weeks for a maximum of 8 cycles

Primary Outcome Measures :
  1. Progression-Free Survival (PFS) [ Time Frame: every 6-8-12 weeks ]
    Defined as the time from the date of randomization until disease progression, or death

Secondary Outcome Measures :
  1. Overall survival (OS) [ Time Frame: every 6- 8 -12 weeks ]
    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

  2. Response Rate (RR) [ Time Frame: every 6 - 8 -12 weeks ]
    Measured both according to RECIST criteria

  3. Disease Control Rate (DCR) [ Time Frame: every 6 - 8 -12 weeks ]
    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

  4. Duration of Disease Control [ Time Frame: every 6 - 8 -12 weeks ]
    Measured from the date of randomization until disease progression, or death due to any cause

  5. Safety and Toxicity according to NCI-CTCAE criteria (version 4.03) [ Time Frame: During the study ]

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

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)
  • Good clinical Conditions
  • Normal cardiac function
  • Adequate baseline bone marrow, hepatic and renal function
  • 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

Exclusion Criteria:

  • Patients may 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01358071

Ospedale San Raffaele
Milan, Italy, 20132
Fondazione IRCCS Istituto Nazionale dei Tumori
Milan, Italy, 20133
Istituto Europeo di Oncologia
Milan, Italy, 20141
Istituto Nazionale Tumori IRCCS Fondazione "Giovanni Pascale"
Naples, Italy, 80131
Ospedale S. Maria della Misericordia
Perugia, Italy, 06156
Policlinico Universitario "Agostino Gemelli"
Rome, Italy, 00168
United Kingdom
Beatson Oncology Centre, Gartnavel Hospital
Glasgow, Scotland, United Kingdom, G12 0YN
Clatterbridge Centre for Oncology
Bebington, Wirral, United Kingdom, CH63 4JY
Sponsors and Collaborators
MolMed S.p.A.
Study Director: Antonio Lambiase, MD MolMed S.p.A.

Responsible Party: MolMed S.p.A. Identifier: NCT01358071     History of Changes
Other Study ID Numbers: NGR018
2010-023613-61 ( EudraCT Number )
First Posted: May 23, 2011    Key Record Dates
Last Update Posted: October 9, 2015
Last Verified: October 2015

Keywords provided by MolMed S.p.A.:
Pegylated liposomal doxorubicin
Progression or recurrence Ovarian Cancer
Ovarian Cancer
Advanced or metastatic

Additional relevant MeSH terms:
Ovarian Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Liposomal doxorubicin
Antibiotics, Antineoplastic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action