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

Tracking Information
First Submitted Date ICMJE	January 27, 2010
First Posted Date ICMJE	January 28, 2010
Last Update Posted Date	February 25, 2014
Study Start Date ICMJE	November 2005
Actual Primary Completion Date	April 2008 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: January 27, 2010)	To determine the maximum tolerated dose (MTD) and recommended dose (RD) of the human L19IL2 fusion-cytokine. [ Time Frame: 21 days ]
Original Primary Outcome Measures ICMJE	Same as current
Change History	Complete list of historical versions of study NCT01058538 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: January 27, 2010)	To determine the pharmacokinetic profile. [ Time Frame: 5 days ]; To determine the qualitative and quantitative toxicity profile. [ Time Frame: 21 days ]; To assess the presence of anti-fusion protein antibodies in treated patients. [ Time Frame: 18 weeks ]; To evaluate the safety profile of repeated administrations of L19IL2 in patients treated at the RD. [ Time Frame: 1 year ]; To identify early signs of antitumour activity. [ Time Frame: 1 year ]
Original Secondary Outcome Measures ICMJE	Same as current
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	A Dose Finding Pharmacokinetic Study of the Tumour-targeting Human L19IL2 Monoclonal Antibody-Cytokine Fusion Protein in Patients With Advanced Solid Tumours
Official Title ICMJE	A Dose Finding Pharmacokinetic Study of the Tumour-targeting Human L19IL2 Monoclonal Antibody-Cytokine Fusion Protein in Patients With Advanced Solid Tumours
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.
Study Type ICMJE	Interventional
Study Phase	Phase 1; Phase 2
Study Design ICMJE	Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Advanced Solid Tumours
Intervention ICMJE	Drug: L19IL2; Route: i.v. infusion (60 min) Patients will receive a minimum of 2 cycles of treatment. Each cycle is comprised of treatment on Days 1, 3 and 5 followed by a 16 days rest (1 cycle= 21 days). Patients may receive up to 4 further cycles of treatment (max. of 6 cycles in total). Patients will be initially recruited into the study in cohorts of 3 and the starting dose of L19IL2 will be 5 Mio IU IL2 equivalent. Five steps of dose escalation are planned: 5, 10, 20, 30 and 40 Mio IU IL2 equivalent). After the MTD has been established, the RD will be determined. A further 12 patients (with RCC) will receive the RD dose for a minimum of 2 cycles. For patients in the RD part of the study, patients can switch to maintenance therapy. Maintenance therapy consists of 15 Mio IU IL2 every 2 weeks. The maximum duration of the study for a patient is 12 months.
Study Arms	Experimental: L19IL2; Intervention: Drug: L19IL2
Publications *	Johannsen M, Spitaleri G, Curigliano G, Roigas J, Weikert S, Kempkensteffen C, Roemer A, Kloeters C, Rogalla P, Pecher G, Miller K, Berndt A, Kosmehl H, Trachsel E, Kaspar M, Lovato V, González-Iglesias R, Giovannoni L, Menssen HD, Neri D, de Braud F. The tumour-targeting human L19-IL2 immunocytokine: preclinical safety studies, phase I clinical trial in patients with solid tumours and expansion into patients with advanced renal cell carcinoma. Eur J Cancer. 2010 Nov;46(16):2926-35. doi: 10.1016/j.ejca.2010.07.033. Epub 2010 Aug 24.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: January 27, 2010)	33
Original Actual Enrollment ICMJE	Same as current
Actual Study Completion Date	November 2009
Actual Primary Completion Date	April 2008 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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 </=1.; 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 </=2.; 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.; Pulse oximetry >94% on room air.; Negative serum pregnancy test for females of childbearing potential within 14 days of starting treatment.; Life expectancy of at least 3 months.; Evidence of a personally signed and dated informed consent indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the study.; Willingness and ability to comply with the scheduled visits, treatment plan, laboratory tests and other study procedures.; Negative human immunodeficiency virus (HIV) test 2 to 3 weeks before administration of study treatment (with informed consent for test taken). 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.; Recovery from major trauma including surgery within 4 weeks of administration of study treatment.; Known history of allergy to intravenously administered proteins/peptides/antibodies.; Pregnancy or breast feeding. Female patients must agree to use effective contraception, or be surgically sterile or postmenopausal. The definition of effective contraception will be based on the judgement of the principal investigator or a designated associate.; Chemotherapy (standard or experimental) within 4 weeks of the administration of study treatment, or 6 weeks for nitrous ureas, l-phenylalanine mustard (LPAM) or temozolamide.; Radiation therapy within 4 weeks of the administration of study treatment.; Previous in vivo exposure to monoclonal antibodies for biological therapy in the 6 weeks before administration of study treatment.; Growth factors or immunomodulatory agents within 7 days of the administration of study treatment.; Prior allografts (including bone marrow or stem cells).; Patient requires or is taking corticosteroids or other immunosuppressant drugs on a long term basis. Limited use of corticosteroids to treat or prevent acute hypersensitivity reactions is not considered an exclusion criterion.; Investigational study drug taken within 4 weeks of the administration of study treatment or concurrent treatment with other anti-cancer therapy.
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years and older (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Germany, Italy
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01058538
Other Study ID Numbers ICMJE	PH-L19IL2-01/05; 2005-002716-16 ( EudraCT Number )
Has Data Monitoring Committee	No
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Philogen S.p.A.
Study Sponsor ICMJE	Philogen S.p.A.
Collaborators ICMJE	INC Research
Investigators ICMJE	Principal Investigator: Filippo De Braud, Dr European Institute of Oncology Milan (Italy) Principal Investigator: Manfred Johannsen, Dr Champus Charitè Mitte Berlin (Germany)
PRS Account	Philogen S.p.A.
Verification Date	February 2014
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP