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

Phase 2

Completed

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

• Registration Number: NCT01358071
• Lead Sponsor: AGC Biologics S.p.A.

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.

Study Timeline

• Study First Submitted: 2011-05-19
• Study First Submitted QC: 2011-05-20
• Study First Posted: 2011-05-23
• Study Start: 2011-06
• Primary Completion: 2016-12
• Study Completion: 2016-12
• Status Verified: 2018-09
• Last Update Submitted: 2018-09-25
• Last Update Posted: 2018-09-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 119

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.

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	NGR-hTNF	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

Primary Outcome Measures

Name	Time	Method
Progression-Free Survival (PFS)	from the date of randomization, every 6 and 8 weeks based on type of chemotherapy during treatment and every 12 weeks during the follow-up until PD or death	Defined as the time from the date of randomization until disease progression, or death

Secondary Outcome Measures

Name	Time	Method
Response Rate (RR)	from the date of randomization, every 6 and 8 weeks based on type of chemotherapy during treatment and every 12 weeks during the follow-up until PD or death	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 the date of randomization, every 6 and 8 weeks based on type of chemotherapy during treatment and every 12 weeks during the follow-up until PD or death	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 the date of randomization, every 6 and 8 weeks based on type of chemotherapy during treatment and every 12 weeks during the follow-up until PD or death	measured from the date of randomization until disease progression, or death due to any cause.
Safety and Toxicity according to NCI-CTCAE criteria (version 4.03)	from the start of treatment until 28 days after last treatment	To evaluate safety and toxicity profile related to NGR-hTNF
Overall survival (OS)	from the date of randomization, every 6 and 8 weeks based on type of chemotherapy during treatment and every 12 weeks during follow-up until death	defined as the time from the date of randomization until death due to any cause.

Trial Locations

Locations (8)

Beatson Oncology Centre, Gartnavel Hospital; 🇬🇧 Glasgow, Scotland, United Kingdom

Clatterbridge Centre for Oncology; 🇬🇧 Bebington, Wirral, United Kingdom

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

Ospedale San Raffaele; 🇮🇹 Milan, Italy

Ospedale S. Maria della Misericordia; 🇮🇹 Perugia, Italy

Istituto Europeo di Oncologia; 🇮🇹 Milan, Italy

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

Policlinico Universitario "Agostino Gemelli"; 🇮🇹 Rome, Italy