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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00305084
Recruitment Status : Completed
First Posted : March 21, 2006
Last Update Posted : January 29, 2013
Information provided by:
MolMed S.p.A.

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 ).

Condition or disease Intervention/treatment Phase
Cancer Drug: NGR-hTNF Drug: Doxorubicin Phase 1

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 15 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (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
Study Start Date : January 2006
Actual Primary Completion Date : May 2007
Actual Study Completion Date : April 2008

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
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)

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

Secondary Outcome Measures :
  1. To evaluate the pharmacokinetic profiles of NGR-hTNF and doxorubicin [ Time Frame: during and following treatment ]
  2. To measure sTNFRs and anti-NGR-hTNF antibody plasma levels [ Time Frame: before and following treatment ]
  3. To evaluate phenotype analysis and adaptative immune response [ Time Frame: during the study ]
  4. 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 ]

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00305084

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

Responsible Party: Molmed Identifier: NCT00305084     History of Changes
Other Study ID Numbers: NGR003
EUDRACT Number: 2005-004846-15
First Posted: March 21, 2006    Key Record Dates
Last Update Posted: January 29, 2013
Last Verified: January 2013

Keywords provided by MolMed S.p.A.:
solid tumors

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