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

Phase 2

Completed

• Conditions: Ovarian Cancer
• Interventions: Drug: Pegylated liposomal doxorubicin; Drug: NGR-hTNF; Drug: Doxorubicin

• Registration Number: NCT03804866
• Lead Sponsor: AGC Biologics S.p.A.

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

Study Timeline

• Study Start: 2013-03
• Primary Completion: 2016-12
• Study Completion: 2016-12
• Study First Submitted: 2018-10-03
• Status Verified: 2019-01
• Study First Submitted QC: 2019-01-14
• Last Update Submitted: 2019-01-14
• Study First Posted: 2019-01-15
• Last Update Posted: 2019-01-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 14

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm B: anthracycline	Pegylated liposomal doxorubicin	Pegylated Liposomal Doxorubicin or Doxorubicin
Arm A: NGR-hTNF+ anthracycline	Pegylated liposomal doxorubicin	NGR-hTNF+Pegylated Liposomal Doxorubicin or Doxorubicin
Arm A: NGR-hTNF+ anthracycline	Doxorubicin	NGR-hTNF+Pegylated Liposomal Doxorubicin or Doxorubicin
Arm B: anthracycline	Doxorubicin	Pegylated Liposomal Doxorubicin or Doxorubicin
Arm A: NGR-hTNF+ anthracycline	NGR-hTNF	NGR-hTNF+Pegylated Liposomal Doxorubicin or Doxorubicin

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Progression-Free Survival (PFS)	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
Overall survival (OS)	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
Response Rate (RR)	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
Disease Control Rate (DCR)	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
Duration of Disease Control	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

Trial Locations

Locations (4)

Istituto Europeo di Oncologia; 🇮🇹 Milan, Italy

Ospedale San Raffaele; 🇮🇹 Milan, Italy

Istituto Nazionale Tumori IRCCS Fondazione "Giovanni Pascale"; 🇮🇹 Naples, Italy

Fondazione IRCCS Istituto Nazionale dei Tumori; 🇮🇹 Milan, Italy