Study of NGR-hTNF in Combination With Doxorubicin in Solid Tumors

NCT ID: NCT00305084

Last Updated: 2019-10-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-02-28
• Study Completion Date: 2007-05-08

Brief Summary

The main objective of the trial is to document the safety of the combination (escalation doses of NGR-hTNF, from 0.2 mcg/sqm to 1.6 mcg/sqm , with a fixed dose of doxorubicin, 75 mg/sqm). Safety will be established by clinical and laboratory assessment according to National Cancer Institute Common Toxicity Criteria (NCI-CTC ).

Detailed Description

This is a phase IB, open-label, non-randomized, dose-escalation study that will be conducted in sequential cohorts of patients. Three patients per each cohort are planned.

Patients, with advanced or metastatic solid tumor previously treated with a non cumulative dose of doxorubicin (<300 mg/sqm in order to allow an adequate number of cycles) or chemotherapy naïve will be enrolled.

Conditions

Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

A

Group Type: EXPERIMENTAL

NGR-hTNF

Intervention Type: DRUG

0.2, 0.4, 0.8 and 1.6 μg/m²as 60-minute intravenous infusion every 3 weeks

Doxorubicin

Intervention Type: DRUG

75 mg/m² intravenous infusion over 15 minutes (starting 1 hour after the end of NGR-hTNF infusion)

Interventions

NGR-hTNF

0.2, 0.4, 0.8 and 1.6 μg/m²as 60-minute intravenous infusion every 3 weeks

Intervention Type: DRUG

Doxorubicin

75 mg/m² intravenous infusion over 15 minutes (starting 1 hour after the end of NGR-hTNF infusion)

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Patients ≥18 years old with proven advanced or metastatic solid tumor not amenable to any clinical improvement by current standard treatments and previously treated with a non cumulative dose of anthracyclines (<300 mg/sqm) or chemotherapy naïve.
• Life expectancy more than 3 months.
• ECOG performance status 0 - 2.
• Normal cardiac function (left ventricular ejection fraction [LVEF] ≥55%) and absence of uncontrolled hypertension.
• Absence of any conditions involving hypervolemia and its consequences.
• 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 x ULN Serum creatinine < 1.5 x ULN

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

• Chemo, radio, hormonal, immuno or anti-vascular therapy: wash-out period of 28 days.
• Surgery: wash-out period of 14 days.
• Patients must give written informed consent to participate in the study.

Exclusion Criteria

• Concurrent anticancer therapy
• Patients must not receive any other investigational agents while on study
• Patients with a LVEF <55%
• New York Heart Association class III or IV cardiac disease
• Acute angina
• Patients with myocardial infarction within the last six (6) months
• Patient with significant peripheral vascular disease
• Thrombosis of main portal vein
• Previous signs of severe toxicity doxorubicin related
• Previous signs of cardiotoxicity doxorubicin related
• Patients previously treated with a cumulative dosage of anthracyclines ≥300 mg/m^2
• 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 child-bearing potential must provide a negative pregnancy test (serum or urine) within 14 days prior to registration

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AGC Biologics S.p.A.

INDUSTRY

Sponsor Role: lead

Responsible Party

Molmed

Principal Investigators

Federico Caligaris Cappio, MD

Role: PRINCIPAL_INVESTIGATOR

Fondazione San Raffaele del Monte Tabor

Locations

Istituto Clinico Humanitas

Rozzano, Milan, Italy

Azienda Ospedaliera Universitaria "San Martino"

Genova, , Italy

Fondazione San Raffaele del Monte Tabor

Milan, , Italy

University Medical Centre, Nijmegen

Nijmegen, , Netherlands

Countries

Italy; Netherlands

References

Sacchi A, Gasparri A, Gallo-Stampino C, Toma S, Curnis F, Corti A. Synergistic antitumor activity of cisplatin, paclitaxel, and gemcitabine with tumor vasculature-targeted tumor necrosis factor-alpha. Clin Cancer Res. 2006 Jan 1;12(1):175-82. doi: 10.1158/1078-0432.CCR-05-1147.

Reference Type: BACKGROUND

PMID: 16397040 (View on PubMed)

Other Identifiers

EUDRACT Number: 2005-004846-15

Identifier Type: -

Identifier Source: secondary_id

NGR003

Identifier Type: -

Identifier Source: org_study_id