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

NCT ID: NCT01358071

Last Updated: 2018-09-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 119 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-06-30
• Study Completion Date: 2016-12-31

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.

Conditions

Ovarian Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A: NGR-hTNF+ anthracycline

NGR-hTNF+Pegylated Liposomal Doxorubicin or Doxorubicin

Group Type: EXPERIMENTAL

NGR-hTNF

Intervention Type: DRUG

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

Intervention Type: DRUG

50 mg/m² iv every 4 weeks until confirmed evidence of disease progression

Doxorubicin

Intervention Type: DRUG

60 mg/m² iv every 3 weeks for a maximum of 8 cycles

Arm B: anthracycline

Pegylated Liposomal Doxorubicin or Doxorubicin

Group Type: ACTIVE_COMPARATOR

Pegylated liposomal doxorubicin

Intervention Type: DRUG

50 mg/m² iv every 4 weeks until confirmed evidence of disease progression

Doxorubicin

Intervention Type: DRUG

60 mg/m² iv every 3 weeks for a maximum of 8 cycles

Interventions

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

Intervention Type: DRUG

Pegylated liposomal doxorubicin

50 mg/m² iv every 4 weeks until confirmed evidence of disease progression

Intervention Type: DRUG

Doxorubicin

60 mg/m² iv every 3 weeks for a maximum of 8 cycles

Intervention Type: DRUG

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:

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

AGC Biologics S.p.A.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Antonio Lambiase, MD

Role: STUDY_DIRECTOR

AGC Biologics S.p.A.

Locations

Ospedale San Raffaele

Milan, , Italy

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, , Italy

Istituto Europeo di Oncologia

Milan, , Italy

Istituto Nazionale Tumori IRCCS Fondazione "Giovanni Pascale"

Naples, , Italy

Ospedale S. Maria della Misericordia

Perugia, , Italy

Policlinico Universitario "Agostino Gemelli"

Rome, , Italy

Beatson Oncology Centre, Gartnavel Hospital

Glasgow, Scotland, United Kingdom

Clatterbridge Centre for Oncology

Bebington, Wirral, United Kingdom

Countries

Italy; United Kingdom

Other Identifiers

2010-023613-61

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

NGR018

Identifier Type: -

Identifier Source: org_study_id