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

NCT01058538 | Completed Phase 1

• 2 other identifiers: PH-L19IL2-01/052005-002716-16
• Study Type: interventional
• Target: 33
• Locations: 2 countries
• Sites: 2

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).

Conditions

Advanced Solid Tumours

Keywords

Interleukin, IL2, monoclonal, antibody, cytokine, tumour targeting, solid tumours, dose finding, renal cell carcinoma, fusion protein, RCC,; L19

Outcome Measures

Primary Outcomes (1)

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

  21 days

Secondary Outcomes (5)

• To determine the pharmacokinetic profile.

  5 days

• 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 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

Study Arms (1)

L19IL2

EXPERIMENTAL

Drug: L19IL2

Interventions

L19IL2 DRUG

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.

L19IL2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Philogen S.p.A.: lead
• Syneos Health: collaborator

Study Sites (2)

Campus Charité Mitte

Berlin, 10117, Germany

Location

European Institute of Oncology

Milan, 20141, Italy

Location

Related Publications (1)

• 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, Gonzalez-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.

  PMID: 20797845 DERIVED

MeSH Terms

Conditions

Carcinoma, Renal Cell

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Study Officials

• Filippo De Braud, Dr

  European Institute of Oncology Milan (Italy)

  PRINCIPAL INVESTIGATOR

• Manfred Johannsen, Dr

  Champus Charitè Mitte Berlin (Germany)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 27, 2010
• First Posted: January 28, 2010
• Study Start: November 1, 2005
• Primary Completion: April 1, 2008
• Study Completion: November 1, 2009
• Last Updated: February 25, 2014

Record last verified: 2014-02

Locations

DE (1); IT (1)