Phase 1
Completed N=15
Study of NGR-hTNF in Combination With Doxorubicin in Solid Tumors
Source: ClinicalTrials.gov NCT00305084 ↗Enrolled (actual)
15
Serious AEs
60.0%
Results posted
Oct 2019
Primary outcomePrimary: Number of Adverse Events From Escalating Doses of NGR-hTNF in Combination With a Fixed Dose of Doxorubicin — 59; 142; 67; 101 Adverse event
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 ).
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Adverse Events From Escalating Doses of NGR-hTNF in Combination With a Fixed Dose of Doxorubicin |
59; 142; 67; 101; 124 | — |
| SECONDARY Pharmacokinetic Profiles of NGR-hTNF Administrated in Combination With Doxorubicin (Cmax) |
2.22; 1.82; 4.44; 8.10; 15.7; 3.10 | — |
| SECONDARY Pharmacokinetic Profiles of NGR-hTNF Administrated in Combination With Doxorubicin (Tmax) |
0.25; 2.50; 2.50; 0.78; 2.83; 0.87 | — |
| SECONDARY Pharmacokinetic Profiles of NGR-hTNF Administrated in Combination With Doxorubicin (AUC0-t(Last)) |
1.94; 1.99; 11.8; 12.0; 25.7; 7.84 | — |
| SECONDARY sTNFRs and Anti-NGR-hTNF Antibody Plasma Levels (Emax) |
0.34; -0.19; 0.21; 0.59; 1.64; 0.01 | — |
| SECONDARY sTNFRs and Anti-NGR-hTNF Antibody Plasma Levels (Tmax) |
5.47; 2.17; 4.33; 3.78; 2.83; 3.19 | — |
| SECONDARY sTNFRs and Anti-NGR-hTNF Antibody Plasma Levels (ARC) |
0.1; -3.52; -0.64; 2.11; 3.38; -1.04 | — |
| SECONDARY sTNFRs and Anti-NGR-hTNF Antibody Plasma Levels (Eav) |
0.02; -0.59; -0.11; 0.35; 0.56; -0.17 | — |
| SECONDARY To Evaluate Phenotype Analysis and Adaptative Immune Response |
— | — |
| SECONDARY Signs of Anticancer Activity by Standard Imaging or Clinically; When Possible Tumor Response Will be Documented According to RECIST Criteria |
2; 3; 3; 2; 3; 1 | — |
Eligibility 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 ( 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
Data sourced from ClinicalTrials.gov (NCT00305084). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.