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

NCT ID: NCT03804866

Last Updated: 2019-01-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 14 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-03-31
• Study Completion Date: 2016-12-31

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

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 every week 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 every week 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 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

• 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

Countries

Italy

Other Identifiers

2012-005745-20

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

NGR018-IPR/26

Identifier Type: -

Identifier Source: org_study_id