A Dose Finding Pharmacokinetic Study of the Tumour-targeting Human L19IL2 Monoclonal Antibody-Cytokine Fusion Protein in Patients With Advanced Solid Tumours

Philogen S.p.A.2 sites in 2 countries33 target enrollmentNovember 2005

ConditionsAdvanced Solid Tumours

InterventionsL19IL2

DrugsL19IL2

Overview

Phase: Phase 1
Intervention: L19IL2
Conditions: Advanced Solid Tumours
Sponsor: Philogen S.p.A.
Enrollment: 33
Locations: 2
Primary Endpoint: To determine the maximum tolerated dose (MTD) and recommended dose (RD) of the human L19IL2 fusion-cytokine.
Status: Completed
Last Updated: 12 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is a Phase I/II study for patients with solid tumors and renal cell carcinoma (RCC; for the Phase II part). L19-IL2 is a tumor targeted immunocytokine constituted of a single chain Fragment variable (scFv) format directed against the ED-B domain of fibronectin, one of the most important markers for neoangiogenesis, and the human cytokine interleukin-2 (IL2).

Detailed Description

This is an open-label, non-randomised, multicentre, Phase I/II study to assess safety, pharmacokinetics (PK), and early signs of activity of L19-IL2 monotherapy. In the first part of the study, there will be 5 dose escalation steps in sequential cohorts of patients with advanced solid tumours. In the second part of the study, patients with advanced RCC will be given a fixed dose of L19IL2 at the RD.

Registry

clinicaltrials.gov

Start Date

November 2005

End Date

November 2009

Last Updated

12 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Philogen S.p.A.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•For the first part of the study: histologically or cytologically confirmed solid cancer with evidence of advanced disease for which no other standard treatment is available or appropriate. For the second part of the study: Histologically or cytologically confirmed advanced RCC.
•Patients must have at least one measurable lesion as detected by computed tomography (CT).
•All acute toxic effects (excluding alopecia) of any prior therapy must have resolved to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (v3.0) Grade \</=
•Patients who have received autologous marrow/stem cell infusion using monoclonal antibody-purged specimens are eligible.
•Adult patients of both sexes aged 18 years or older.
•Eastern Cooperative Oncology Group (ECOG) performance status \</=
•Sufficient haematological, liver and renal function:
•Absolute neutrophil count (ANC) \>/=1.5 x 109/L, platelets \>/=100 x 109/L, haemoglobin (Hb) \>/=9.0 g/dL,
•Alkaline phosphatase (AP) \</=3 x upper limit of the reference range (ULN) and alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) \</=3 x ULN, and bilirubin \<1.5 x ULN; however, in the presence of liver metastases, AP \</=5 x ULN and ALT and/or AST \</=5 x ULN, and bilirubin \<1.5 x ULN,
•Creatinine \</=ULN, or 24 h creatinine clearance \>/=50 mL/min.

Exclusion Criteria

•Presence of active infections (eg requiring antibiotic therapy) or other severe concurrent disease, which, in the opinion of the investigator, would place the patient at undue risk or interfere with the study.
•Presence of known brain metastases.
•Chronic aggressive hepatitis or active autoimmune diseases.
•History within the last year of acute or subacute coronary syndromes including myocardial infarction, unstable or severe stable angina pectoris.
•Heart insufficiency (\>Grade II New York Heart Association \[NYHA\] criteria).
•Irreversible cardiac arrhythmias requiring permanent medication.
•Uncontrolled hypertension.
•Ischaemic peripheral vascular disease (Grade IIb-IV).
•Severe rheumatoid arthritis.
•Severe diabetic retinopathy.

Arms & Interventions

L19IL2

Intervention: L19IL2

Outcomes

Primary Outcomes

To determine the maximum tolerated dose (MTD) and recommended dose (RD) of the human L19IL2 fusion-cytokine.

Time Frame: 21 days

Secondary Outcomes

To determine the qualitative and quantitative toxicity profile.(21 days)
To assess the presence of anti-fusion protein antibodies in treated patients.(18 weeks)
To determine the pharmacokinetic profile.(5 days)
To evaluate the safety profile of repeated administrations of L19IL2 in patients treated at the RD.(1 year)
To identify early signs of antitumour activity.(1 year)