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

Ovarian Cancer Clinical Trial

— NGR018  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01358071
• Other study ID #: NGR018
• Secondary ID: 2010-023613-61
• Status: Completed
• Phase: Phase 2
• Start date: June 2011
• Est. completion date: December 2016

Study information

• Verified date: September 2018
• Source: MolMed S.p.A.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 119
• Est. completion date: December 2016
• Est. primary completion date: December 2016
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Neoplasms, Glandular and Epithelial
• Ovarian Cancer
• Ovarian Neoplasms

Intervention

Drug:
• NGR-hTNF
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
• Pegylated liposomal doxorubicin
50 mg/m² iv every 4 weeks until confirmed evidence of disease progression
• Doxorubicin
60 mg/m² iv every 3 weeks for a maximum of 8 cycles

Locations

Country	Name	City	State
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori	Milan
Italy	Istituto Europeo di Oncologia	Milan
Italy	Ospedale San Raffaele	Milan
Italy	Istituto Nazionale Tumori IRCCS Fondazione "Giovanni Pascale"	Naples
Italy	Ospedale S. Maria della Misericordia	Perugia
Italy	Policlinico Universitario "Agostino Gemelli"	Rome
United Kingdom	Clatterbridge Centre for Oncology	Bebington	Wirral
United Kingdom	Beatson Oncology Centre, Gartnavel Hospital	Glasgow	Scotland

Sponsors (1)

Lead Sponsor	Collaborator
MolMed S.p.A.

Countries where clinical trial is conducted

Italy,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-Free Survival (PFS)	Defined as the time from the date of randomization until disease progression, or death	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	Overall survival (OS)	defined as the time from the date of randomization until death due to any cause.	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
Secondary	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.	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	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.	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	Duration of Disease Control	measured from the date of randomization until disease progression, or death due to any cause.	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	Safety and Toxicity according to NCI-CTCAE criteria (version 4.03)	To evaluate safety and toxicity profile related to NGR-hTNF	from the start of treatment until 28 days after last treatment