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Advanced Solid TumoursPhase 1/2NCT01058538

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

A Phase 1/2 study testing L19IL2 in people with Advanced Solid Tumours, run by Philogen S.p.A. at 2 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Advanced Solid Tumours
What is being tested?
L19IL2
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
33 participants
Where
2 sitesin 2 countries
Study dates
Nov 2005to Nov 2009
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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).

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

2 sites in 2 countries.

2 sites in 2 countries

Germany1 site

  • Campus Charité Mitte

    Berlin, 10117

Other trials in Germany

Italy1 site

  • European Institute of Oncology

    Milan, 20141

Other trials in Italy

About this study

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).

Read the 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.

Being tested
L19IL2
Keywords
Interleukin, IL2, monoclonal, antibody, cytokine, tumour targeting, solid tumours, dose finding, renal cell carcinoma, fusion protein, RCC,, L19
Medical subject headings
Carcinoma, Renal Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • L19IL2Drug

    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 groups in NCT01058538
Study groupRoleWhat they receive
L19IL2ExperimentalNot described
Receives: Drug: L19IL2

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: 21 days

Secondary outcomes (5)

  1. To determine the pharmacokinetic profile.

    Measured: 5 days

  2. To determine the qualitative and quantitative toxicity profile.

    Measured: 21 days

  3. To assess the presence of anti-fusion protein antibodies in treated patients.

    Measured: 18 weeks

  4. To evaluate the safety profile of repeated administrations of L19IL2 in patients treated at the RD.

    Measured: 1 year

  5. To identify early signs of antitumour activity.

    Measured: 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Jan 2010 (estimated)
  2. Study startNov 2005
  3. Primary completionApr 2008
  4. Study completionNov 2009

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
33 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01058538
Sponsor's protocol ID
PH-L19IL2-01/05
Other IDs
2005-002716-16, 2005
Status last verified
Feb 2014
First submitted
27 Jan 2010
Last updated
25 Feb 2014
Results posted
No
Data monitoring committee
No

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, 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.

    PubMed 20797845

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing L19IL2 in people with Advanced Solid Tumours, run by Philogen S.p.A. at 2 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Feb 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Germany, Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

To determine the maximum tolerated dose (MTD) and recommended dose (RD) of the human L19IL2 fusion-cytokine. (time frame: 21 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01058538, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Feb 2014.

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