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

NCT00305084 | Completed Phase 1 Results

• 2 other identifiers: NGR003EUDRACT Number: 2005-004846-15
• Study Type: interventional
• Target: 15
• Locations: 2 countries
• Sites: 4

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 ).

Conditions

Cancer

Keywords

NGR-hTNF; doxorubicin; solid tumors

Outcome Measures

Primary Outcomes (1)

• Number of Adverse Events From Escalating Doses of NGR-hTNF in Combination With a Fixed Dose of Doxorubicin

  An Adverse Event (AE) is any untoward medical occurrence or experience in a patient or clinical investigation subject treated administered a pharmaceutical product and which does not necessarily have to have a casual relationship with this treatment. An adverse event (AE) can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.

  Through study completion, an average of 1 year

Secondary Outcomes (9)

• Pharmacokinetic Profiles of NGR-hTNF Administrated in Combination With Doxorubicin (Cmax)

  prior to infusion and 15', 30', 60', 90', 120', 134' [1 minute before the end of doxorubicin administration], 180', 240', 360' minutes

• Pharmacokinetic Profiles of NGR-hTNF Administrated in Combination With Doxorubicin (Tmax)

  prior to infusion and 15', 30', 60', 90', 120', 134' [1 minute before the end of doxorubicin administration], 180', 240', 360' minutes

• Pharmacokinetic Profiles of NGR-hTNF Administrated in Combination With Doxorubicin (AUC0-t(Last))

  prior to infusion and 15', 30', 60', 90', 120', 134' [1 minute before the end of doxorubicin administration], 180', 240', 360' minutes

• sTNFRs and Anti-NGR-hTNF Antibody Plasma Levels (Emax)

  prior to infusion and 15', 30', 60', 90', 120', 134' [1 minute before the end of doxorubicin administration], 180', 240', 360' minutes

• sTNFRs and Anti-NGR-hTNF Antibody Plasma Levels (Tmax)

  prior to infusion and 15', 30', 60', 90', 120', 134' [1 minute before the end of doxorubicin administration], 180', 240', 360' minutes

Study Arms (1)

A

EXPERIMENTAL

Drug: NGR-hTNF; Drug: Doxorubicin

Interventions

NGR-hTNF DRUG

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

A

Doxorubicin DRUG

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

A

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• AGC Biologics S.p.A.: lead

Study Sites (4)

Istituto Clinico Humanitas

Rozzano, Milan, 20089, Italy

Location

Azienda Ospedaliera Universitaria "San Martino"

Genova, 16132, Italy

Location

Fondazione San Raffaele del Monte Tabor

Milan, 20132, Italy

Location

University Medical Centre, Nijmegen

Nijmegen, Netherlands

Location

Related Publications (1)

• 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.

  PMID: 16397040 BACKGROUND

MeSH Terms

Conditions

Neoplasms

Interventions

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

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: MolMed S.p.A.
• Organization: Clinical Operations

clinical.operations@molmed.com

0039 02212771

Study Officials

• Federico Caligaris Cappio, MD

  Fondazione San Raffaele del Monte Tabor

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY

Model Details: Dose-escalating study

Study Record Dates

• First Submitted: March 15, 2006
• First Posted: March 21, 2006
• Study Start: February 28, 2006
• Primary Completion: May 8, 2007
• Study Completion: May 8, 2007
• Last Updated: October 4, 2019
• Results First Posted: October 4, 2019

Record last verified: 2019-09

Locations

IT (3); NL (1)