Study of NGR-hTNF in Combination With Cisplatin in Solid Tumor

NCT00483093 | Completed Phase 1

• 2 other identifiers: NGR0042006-006035-42
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 2

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 cisplatin, 80 mg/sqm). Safety will be established by clinical and laboratory assessment according to National Cancer Institute Common Toxicity Criteria (NCI-CTC ).

Conditions

Solid Tumors

Keywords

NGR-hTNF; cisplatin; solid tumors

Outcome Measures

Primary Outcomes (1)

• To verify the safety of escalating doses of NGRhTNF (from 0.2 to 1.6 µg/m^2) in combination with cisplatin (80 mg/m^2) every 3 weeks

  To recommend a dose regimen of NGR-hTNF + Cisplatin for future phase II trials

Secondary Outcomes (3)

• To document the preliminary antitumor activity of the combination in terms of objective response rate according to RECIST criteria

  every six weeks

• To evaluate the pharmacokinetic profiles of the combination of NGR-hTNF and cisplatin

  During the study

• To measure plasma levels of sTNFRs and anti-NGR-hTNF antibodies

  During the study

Study Arms (1)

A

EXPERIMENTAL

Drug: NGR-hTNF; Drug: Cisplatin

Interventions

NGR-hTNF DRUG

iv q3W escalating dose NGR-hTNF up to 1.6 mcg/sqm

A

Cisplatin DRUG

iv q3W 80 mg/sqm 30 minutes after NGR-hTNF infusion for a maximum of six cycles

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 with advanced or metastatic solid tumor not amenable to any clinical improvement by current standard treatments and suitable for a treatment with cisplatin
• Life expectancy more than 3 months
• ECOG Performance status 0-1
• Absence of any conditions in which hypervolemia and its consequences (e.g. increased stroke volume, elevated blood pressure) may represent a risk for the patient
• 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
• Creatinine clearance (estimated according to Cockcroft-Gault formula) ≥ 50 ml/min
• Patients may have had prior therapy providing the following conditions are met:
• Chemotherapy, radiation therapy, hormonal therapy or immunotherapy: wash-out period of 28 days
• Corticosteroid therapy wash out period of 14 days
• Surgery: wash-out period of 14 days

You may not qualify if:

• Previous signs of severe toxicity platinum related
• Patients must not receive any other investigational agents while on study
• New York Heart Association class III or IV cardiac disease
• Unstable angina
• Patients with myocardial infarction within the last six (6) months
• Patient with significant peripheral vascular disease
• 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

Sponsors & Collaborators

• AGC Biologics S.p.A.: lead

Study Sites (2)

Fondazione San Raffaele del Monte Tabor

Milan, Milan,, Italy

Location

Istituto Europeo Oncologico

Milan, Milan, Italy

Location

Related Publications (1)

• Gregorc V, De Braud FG, De Pas TM, Scalamogna R, Citterio G, Milani A, Boselli S, Catania C, Donadoni G, Rossoni G, Ghio D, Spitaleri G, Ammannati C, Colombi S, Caligaris-Cappio F, Lambiase A, Bordignon C. Phase I study of NGR-hTNF, a selective vascular targeting agent, in combination with cisplatin in refractory solid tumors. Clin Cancer Res. 2011 Apr 1;17(7):1964-72. doi: 10.1158/1078-0432.CCR-10-1376. Epub 2011 Feb 9.

  PMID: 21307147 RESULT

MeSH Terms

Interventions

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

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Antonio Lambaise, MD

  AGC Biologics S.p.A.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 5, 2007
• First Posted: June 6, 2007
• Study Start: July 1, 2007
• Primary Completion: June 1, 2010
• Study Completion: April 1, 2013
• Last Updated: May 30, 2014

Record last verified: 2014-05

Locations

IT (2)