Clinical trial NCT03804866: NGR-hTNF in Combination With an Anthracycline in Platinum-resistant Ovarian Cancer (NGR018)
Official title: NGR018: Randomized Phase II Study of NGR-hTNF Plus an Anthracycline Versus an Anthracycline Alone in Platinum-resistant Ovarian Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ovarian Cancer
Keywords: NGR-hTNF
Pegylated liposomal doxorubicin
Doxorubicin
Platinum-resistant
Progression or recurrence Ovarian Cancer
Ovarian Cancer
Advanced or metastatic
Lead sponsor: AGC Biologics S.p.A.
Sponsor class: INDUSTRY
First posted: 2019-01-15
Enrollment: 14
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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

Primary outcomes:
measure: Safety according to NCI-CTCAE criteria (version 4.03)
timeFrame: from the start of treatment until 28 days after last treatment
Secondary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: 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
measure: Overall survival (OS)
timeFrame: 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
measure: Response Rate (RR)
timeFrame: 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
measure: Disease Control Rate (DCR)
timeFrame: 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
measure: Duration of Disease Control
timeFrame: 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
Other outcomes:
Locations:
city: Milan
country: Italy
facility: Ospedale San Raffaele
city: Milan
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
city: Milan
country: Italy
facility: Istituto Europeo di Oncologia
city: Naples
country: Italy
facility: Istituto Nazionale Tumori IRCCS Fondazione "Giovanni Pascale"
Study officials:
affiliation: AGC Biologics S.p.A.
name: Antonio Lambiase, MD
role: STUDY_DIRECTOR
References: