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

Phase 2

Completed

• Conditions: Malignant Pleural Mesothelioma
• Interventions: Drug: NGR-hTNF

• Registration Number: NCT00484276
• Lead Sponsor: AGC Biologics S.p.A.

Brief Summary

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.

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 Timeline

• Study Start: 2007-05
• Study First Submitted: 2007-06-07
• Study First Submitted QC: 2007-06-07
• Study First Posted: 2007-06-08
• Primary Completion: 2013-03
• Study Completion: 2013-03
• Status Verified: 2019-01
• Last Update Submitted: 2019-01-14
• Last Update Posted: 2019-01-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 57

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
NGR-hTNF	NGR-hTNF	NGR-hTNF: 0.8 mcg/m² as 60 minutes intravenous infusion every 3 weeks or weekly

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (4)

Istituto Clinico Humanitas; 🇮🇹 Rozzano, Milan, Italy

Istituto Nazionale dei Tumori; 🇮🇹 Milan, Italy

Fondazione San Raffaele del Monte Tabor; 🇮🇹 Milan, Italy

Istituto Europeo Oncologico; 🇮🇹 Milan, Italy