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

AGC Biologics

Status and phase

Completed

Phase 1

Conditions

Cancer

Treatments

Drug: Doxorubicin

Drug: NGR-hTNF

Study type

Interventional

Funder types

Industry

Identifiers

NCT00305084

NGR003

EUDRACT Number: 2005-004846-15

Details and patient eligibility

About

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 ).

Full 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.

Enrollment

15 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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