Study of NGR-hTNF as Single Agent in Patients Affected by Advanced or Metastatic Malignant Pleural Mesothelioma (NGR010)

NGR010: A Phase II Study of NGR-hTNF Administered as Single Agent Every 3 Weeks or Weekly in Patients Affected by Advanced or Metastatic Malignant Pleural Mesothelioma Previously Treated With no More Than One Systemic Therapeutic Regimen

The main objective of the trial is to document the progression free survival (PFS) in advanced or metastatic malignant pleural mesothelioma patients treated with NGR-hTNF as single agent.

Safety will be established by clinical and laboratory assessment according to NCI-CTC criteria.

Study Overview

• Status: Completed
• Conditions: Malignant Pleural Mesothelioma
• Intervention / Treatment: Drug: NGR-hTNF

Detailed Description

This is a phase II, open-label, non-randomized study that will be conducted in patients affected by advanced or metastatic malignant pleural mesothelioma previously treated with no more than one systemic therapeutic regimen , that will be conducted using Simon's two-stage design method.

• Study Type: Interventional
• Enrollment (Actual): 57
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Milan, Italy
    • Istituto Nazionale dei Tumori
  • Milan, Italy
    • Istituto Europeo Oncologico
  • Milan, Italy
    • Fondazione San Raffaele del Monte Tabor
  • Milan
    • Rozzano, Milan, Italy
      • Istituto Clinico Humanitas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients >18 years affected by malignant pleural mesothelioma previously treated with no more than one systemic therapeutic regimen
• Histologically or cytological confirmed malignant pleural mesothelioma of any of the following subtype: epithelial, sarcomatous, mixed
• Prior intrapleural cytotoxic agents including bleomycin not considered systemic chemotherapy
• ECOG Performance status 0 - 2

• Adequate baseline bone marrow, hepatic and renal function, defined as follows:

  • Neutrophils > 1.5 x 10^9/L and platelets > 100 x 10^9/L
  • Bilirubin < 1.5 x ULN
  • AST and/or ALT < 2.5 x ULN in absence of liver metastasis
  • AST and/or ALT < 5 x ULN in presence of liver metastasis
  • Serum creatinine < 1.5 x ULN
• Absence of any conditions in which hypervolemia and its consequences (e.g. increased stroke volume, elevated blood pressure) or haemodilution could represent a risk for the patient (take as reference "Technical data sheet human albumin" specifically used in Pharmacy Department for NGR-hTNF dilution)

• Patients may have had prior therapy providing the following conditions are met:

  • Chemotherapy and radiotherapy: wash-out period of 28 days
  • Surgery: wash-out period of 14 days
• Normal cardiac function and absence of uncontrolled hypertension
• Patients must give written informed consent to participate in the study

Exclusion Criteria:

• Concurrent anticancer therapy
• Patients may not receive any other investigational agents while on study
• Clinical signs of CNS involvement
• 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. Patients - both males and females - with reproductive potential (i.e. menopausal for less than 1-year and not surgically sterilized) must practice effective contraceptive measures throughout the study. Women of childbearing potential must provide a negative pregnancy test (serum or urine) within 14 days prior to registration

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NGR-hTNF; NGR-hTNF: 0.8 mcg/m² as 60 minutes intravenous infusion every 3 weeks or weekly	Drug: NGR-hTNF; iv q3W or q1W 0.8 mcg/sqm NGR-hTNF

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Antitumor activity defined as progression free survival (PFS)	Defined as the time from the date of randomization until disease progression, or death	during the study

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	Defined as the time from the date of randomization until the date of death due to any cause or the last date the patient was known to be alive	from the randomization until to the date of patient death or discontinuation from the study
Tumor Growth Control Rate (TGCR)	Evaluated according to modified RECIST criteria for Malignant Pleural Mesothelioma	Every 6 weeks during study treatment and every 6 weeks during the follow-up before PD
Experimental Imaging Study (DCE-MRI)	To document possible modifications on vessels permeability by imaging techniques	During the treatment
Cmax of NGR-hTNF in patients treated with weekly schedule	to evaluate Cmax of NGR-hTNF administered weekly	During the treatment
AUC(tau) of NGR-hTNF in patients treated with weekly schedule	to evaluate AUC(tau) of NGR-hTNF administered weekly	During the treatment
Safety according to NCI-CTCAE criteria (version 3)	To evaluate safety profile related to NGR-hTNF	During the treatment and during the follow-up

Collaborators and Investigators

• Sponsor: AGC Biologics S.p.A.

Publications and helpful links

General Publications

• Gregorc V, Zucali PA, Santoro A, Ceresoli GL, Citterio G, De Pas TM, Zilembo N, De Vincenzo F, Simonelli M, Rossoni G, Spreafico A, Grazia Vigano M, Fontana F, De Braud FG, Bajetta E, Caligaris-Cappio F, Bruzzi P, Lambiase A, Bordignon C. Phase II study of asparagine-glycine-arginine-human tumor necrosis factor alpha, a selective vascular targeting agent, in previously treated patients with malignant pleural mesothelioma. J Clin Oncol. 2010 May 20;28(15):2604-11. doi: 10.1200/JCO.2009.27.3649. Epub 2010 Apr 20.

Study record dates

Study Major Dates

• Study Start: May 1, 2007
• Primary Completion (Actual): March 1, 2013
• Study Completion (Actual): March 1, 2013

Study Registration Dates

• First Submitted: June 7, 2007
• First Submitted That Met QC Criteria: June 7, 2007
• First Posted (Estimate): June 8, 2007

Study Record Updates

• Last Update Posted (Actual): January 16, 2019
• Last Update Submitted That Met QC Criteria: January 14, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: NGR-hTNF; malignant pleural mesothelioma
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms by Histologic Type; Neoplasms; Lung Diseases; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Adenoma; Neoplasms, Mesothelial; Pleural Neoplasms; Mesothelioma; Mesothelioma, Malignant
• Other Study ID Numbers: NGR010; 2006-005993-39 (EudraCT Number)