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

NGR004:A Phase IB Study of NGR-hTNF in Combination With Cisplatin in Patient Affected by Advanced or Metastatic Solid Tumor

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 ).

Study Overview

• Status: Completed
• Conditions: Solid Tumors
• Intervention / Treatment: Drug: NGR-hTNF; Drug: Cisplatin

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 not amenable of standard therapy will be enrolled.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 1

Contacts and Locations

Study Locations

• Italy
  • Milan, Italy
    • Istituto Europeo Oncologico
  • Milan,
    • Milan, Milan,, Italy
      • Fondazione San Raffaele del Monte Tabor

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 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
• Patients must give written informed consent to participate in the study

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A	Drug: NGR-hTNF; iv q3W escalating dose NGR-hTNF up to 1.6 mcg/sqm; Drug: Cisplatin; iv q3W 80 mg/sqm 30 minutes after NGR-hTNF infusion for a maximum of six cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: AGC Biologics S.p.A.
• Investigators: Study Director: Antonio Lambaise, MD, AGC Biologics S.p.A.

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: July 1, 2007
• Primary Completion (Actual): June 1, 2010
• Study Completion (Actual): April 1, 2013

Study Registration Dates

• First Submitted: June 5, 2007
• First Submitted That Met QC Criteria: June 5, 2007
• First Posted (Estimate): June 6, 2007

Study Record Updates

• Last Update Posted (Estimate): May 30, 2014
• Last Update Submitted That Met QC Criteria: May 29, 2014
• Last Verified: May 1, 2014

More Information

Terms related to this study

• Keywords: cisplatin; NGR-hTNF; solid tumors
• Additional Relevant MeSH Terms: Neoplasms; Antineoplastic Agents; Cisplatin
• Other Study ID Numbers: NGR004; 2006-006035-42 (EudraCT Number)