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

This study has been completed.
Sponsor:
Information provided by:
MolMed S.p.A.
ClinicalTrials.gov Identifier:
NCT00305084
First received: March 15, 2006
Last updated: January 28, 2013
Last verified: January 2013
  Purpose

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 ).


Condition Intervention Phase
Cancer
Drug: NGR-hTNF
Drug: Doxorubicin
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase IB Study of NGR-hTNF in Combination With Doxorubicin in Patients Affected by Advanced or Metastatic Solid Tumors

Resource links provided by NLM:


Further study details as provided by MolMed S.p.A.:

Primary Outcome Measures:
  • To verify the safety of escalating doses of NGR-hTNF in combination with a fixed dose of doxorubicin [ Time Frame: during and following treatment ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To evaluate the pharmacokinetic profiles of NGR-hTNF and doxorubicin [ Time Frame: during and following treatment ] [ Designated as safety issue: No ]
  • To measure sTNFRs and anti-NGR-hTNF antibody plasma levels [ Time Frame: before and following treatment ] [ Designated as safety issue: No ]
  • To evaluate phenotype analysis and adaptative immune response [ Time Frame: during the study ] [ Designated as safety issue: No ]
  • To document signs of anticancer activity by standard imaging or clinically; when possible tumor response will be documented according to RECIST criteria [ Time Frame: During the treatment and during the follow-up ] [ Designated as safety issue: No ]

Enrollment: 15
Study Start Date: January 2006
Study Completion Date: April 2008
Primary Completion Date: May 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A Drug: NGR-hTNF
0.2, 0.4, 0.8 and 1.6 μg/m²as 60-minute intravenous infusion every 3 weeks
Drug: Doxorubicin
75 mg/m² intravenous infusion over 15 minutes (starting 1 hour after the end of NGR-hTNF infusion)

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00305084

Locations
Italy
Istituto Clinico Humanitas
Rozzano, Milan, Italy, 20089
Azienda Ospedaliera Universitaria "San Martino"
Genova, Italy, 16132
Fondazione San Raffaele del Monte Tabor
Milan, Italy, 20132
Netherlands
University Medical Centre, Nijmegen
Nijmegen, Netherlands
Sponsors and Collaborators
MolMed S.p.A.
Investigators
Principal Investigator: Federico Caligaris Cappio, MD Fondazione San Raffaele del Monte Tabor
  More Information

Publications:
Responsible Party: Molmed
ClinicalTrials.gov Identifier: NCT00305084     History of Changes
Other Study ID Numbers: NGR003, EUDRACT Number: 2005-004846-15
Study First Received: March 15, 2006
Last Updated: January 28, 2013
Health Authority: Italy: National Institute of Health
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by MolMed S.p.A.:
NGR-hTNF
doxorubicin
solid tumors

Additional relevant MeSH terms:
Doxorubicin
Liposomal doxorubicin
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 30, 2014