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

NCT03804866 | Completed Phase 2

• 2 other identifiers: NGR018-IPR/262012-005745-20
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 4

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

Conditions

Ovarian Cancer

Keywords

NGR-hTNF; Pegylated liposomal doxorubicin; Doxorubicin; Platinum-resistant; Progression or recurrence Ovarian Cancer; Ovarian Cancer; Advanced or metastatic

Outcome Measures

Primary Outcomes (1)

• Safety according to NCI-CTCAE criteria (version 4.03)

  To evaluate safety profile related to NGR-hTNF

  from the start of treatment until 28 days after last treatment

Secondary Outcomes (5)

• 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

• 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

• 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

• 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

• 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

Study Arms (2)

Arm A: NGR-hTNF+ anthracycline

EXPERIMENTAL

NGR-hTNF+Pegylated Liposomal Doxorubicin or Doxorubicin

Drug: NGR-hTNF; Drug: Pegylated liposomal doxorubicin; Drug: Doxorubicin

Arm B: anthracycline

ACTIVE COMPARATOR

Pegylated Liposomal Doxorubicin or Doxorubicin

Drug: Pegylated liposomal doxorubicin; Drug: Doxorubicin

Interventions

NGR-hTNF DRUG

NGR-hTNF: 0.8 mcg/m² as 60 minutes intravenous infusion every week until confirmed evidence of disease progression or unacceptable toxicity occurs

Arm A: NGR-hTNF+ anthracycline

Pegylated liposomal doxorubicin DRUG

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

Arm A: NGR-hTNF+ anthracycline; Arm B: anthracycline

Doxorubicin DRUG

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

Arm A: NGR-hTNF+ anthracycline; Arm B: anthracycline

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Neutrophils ≥ 1.5 x 109/L; platelets ≥ 100 x 109/L; hemoglobin ≥ 9 g/dL
• Bilirubin ≤ 1.5 x ULN
• AST and/or ALT ≤ 2.5 x ULN in absence of liver metastasis or ≤ 5 x ULN in presence of liver metastasis
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• AGC Biologics S.p.A.: lead

Study Sites (4)

Ospedale San Raffaele

Milan, 20132, Italy

Location

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, 20133, Italy

Location

Istituto Europeo di Oncologia

Milan, 20141, Italy

Location

Istituto Nazionale Tumori IRCCS Fondazione "Giovanni Pascale"

Naples, 80131, Italy

Location

MeSH Terms

Conditions

Ovarian Neoplasms; Disease Progression; Neoplasm Metastasis

Interventions

tumor necrosis factor-alpha, CNGRC fusion protein, human; liposomal doxorubicin; Doxorubicin

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplastic Processes

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Antonio Lambiase, MD

  AGC Biologics S.p.A.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 3, 2018
• First Posted: January 15, 2019
• Study Start: March 1, 2013
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2016
• Last Updated: January 15, 2019

Record last verified: 2019-01

Locations

IT (4)