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Malignant Melanoma, SkinPhase 2NCT02076633

Intratumoral Administration of L19IL2/L19TNF

A Phase 2 study testing L19IL2+L19TNF in people with Malignant Melanoma, Skin, run by Philogen S.p.A. at 2 sites in Italy.

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 Phase II study is an uncontrolled, multicenter, prospective study for patients with malignant melanoma of the skin in clinical stage III or stage IV M1a. Twenty Patients will be treated with a mixture of L19IL2 and L19TNF once weekly for up to 4 weeks. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Malignant Melanoma, Skin
What is being tested?
L19IL2+L19TNF
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
21 participants
Where
2 sitesItaly
Study dates
Dec 2012to May 2015
Phase
Phase 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

  • Histologically confirmed malignant melanoma of the skin in clinical stage III or stage IV M1a
  • Presence of measurable and injectable cutaneous and/or subcutaneous lesions
  • Males or females, age ≥ 18 years
  • ECOG Performance Status/WHO Performance Status ≤ 2
  • Life expectancy of at least 12 weeks
  • Absolute neutrophil count > 1.5 x 10^9/L
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  • Hemoglobin > 9.0 g/dL
  • Platelets > 100 x 10^9/L
  • Total bilirubin ≤ 30 μmol/L (or ≤ 2.0 mg/dl)
  • ALT and AST ≤ 2.5 x the upper limit of normal (ULN)
  • Serum creatinine < 1.5 x ULN
  • LDH serum level within normal range
  • 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) (v4.02) Grade ≤ 1 unless otherwise specified above
  • Negative serum pregnancy test (for women of child-bearing potential only) at screening
  • If of childbearing potential, agreement to use adequate contraceptive methods (e.g., oral contraceptives, condoms, or other adequate barrier controls, intrauterine contraceptive devices, or sterilization) beginning at the screening visit and continuing until 3 months following last treatment with study drug.
  • Able to provide written Informed Consent
  • Willingness and ability to comply with the scheduled visits, treatment plan, laboratory tests and other study procedures.

Who cannot join

  • Uveal melanoma and mucosal melanoma
  • Evidence of visceral metastases and/or active brain metastases at screening
  • Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study except cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (TA, Tis \& Ti) or any cancer curatively treated < 5 years prior to study entry
  • History of HIV infection or infectious hepatitis B or C
  • Presence of active infections (e.g. requiring antimicrobial 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.
  • History within the last year of acute or subacute coronary syndromes including myocardial infarction, unstable or severe autoimmune disease
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  • History of organ allograft or stem cell transplantation
  • Recovery from major trauma including surgery within 4 weeks prior to administration of study treatment.
  • Known history of allergy to IL2, TNF, or other human proteins/peptides/antibodies.
  • Breast feeding female
  • Anti-tumor therapy within 4 weeks of the administration of study treatment (except small surgery).
  • Previous in vivo exposure to monoclonal antibodies for biological therapy in the 6 weeks before administration of study treatment.
  • Planned administration of growth factors or immunomodulatory agents within 7 days before the administration of study treatment
  • Patients in need of systemic treatment for rapidly progressive systemic disease.
  • 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.
  • Any conditions that in the opinion of the investigator could hamper compliance with the study protocol.

Trial locations and contacts

2 sites in 1 country.

Italy2 sites

  • Fondazione IRCCS Istituto Nazionale dei Tumori

    Milan

  • Azienda Ospedaliera Universitaria Senese

    Siena

Other trials in Italy

About this study

Official title: A Phase II Study of Intratumoral Application of L19IL2/L19TNF in Melanoma Patients in Clinical Stage III or Stage IV M1a With Presence of Injectable Cutaneous and/or Subcutaneous Lesions

This Phase II study is an uncontrolled, multicenter, prospective study for patients with malignant melanoma of the skin in clinical stage III or stage IV M1a.

Twenty Patients will be treated with a mixture of L19IL2 and L19TNF once weekly for up to 4 weeks.

The dose will be distributed among the lesions via multiple intralesional injections.

The proportion of patients with complete response at week 12 will be calculated.

Read the detailed description

L19IL2 is a recombinant fusion protein composed of a fully human recombinant monoclonal antibody (L19) and the human recombinant interleukin-2 (IL-2).

IL2, is a potent stimulator of the immune response. It has a central role in the regulation of T cell responses and effects on other immune cells such as natural killer cells, B cells, monocyte/macrophages and neutrophils. IL2 can induce tumor regression through its ability to stimulate a potent cell-mediated immune response in vivo.

L19TNF is a recombinant fusion protein composed of a fully human recombinant monoclonal antibody (L19) and the human tumor necrosis factor-alpha, a primary mediator of immune regulation and inflammation.

As an anti-tumor agent, TNF exerts its major effects via a preferential toxicity for the endothelial cells of the tumor-associated vasculature and an increase of the antitumor immune response. Given at sufficient doses (e.g. intratumorally or in the ILP setting with melphalan), TNF causes significant tumor shrinkage in solid cancer subjects.

This phase II signal generating study is designed to test the efficacy and safety of an intratumorally administered mixture of L19IL2 + L19TNF in patients suffering from metastatic melanoma. It is well documented that the intratumoral administration of IL-2 leads to a high response rate and unexpectedly favorable longtime outcome and several tumor responses have been observed in clinical trials of Philogen, both using intratumorally administered L19IL2 and L19TNF in the ILP setting.

Preclinical data produced within the Philogen group now suggest that the intratumoral administration of a mixture of L19IL2 and L19TNF could be even more effective. After only one intratumoral administration of a mixture of L19IL2 and L19TNF tumors disappeared completely while neither L19IL2 nor L19TNF monotherapy was nearly as effective.

Being tested
L19IL2+L19TNF
Keywords
L19, monoclonal, antibody, IL-2, TNFα, Interleukin, Phase II, metastatic melanoma, clinical stage III, Clinical stage IV M1a
Medical subject headings
Melanoma

What participants receive

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

  • L19IL2+L19TNFDrug

    Patients will be treated with intratumoral injections of 10 MioIU L19IL2 and 312μg L19TNF once weekly for up to 4 weeks.

Study groups in NCT02076633
Study groupRoleWhat they receive
L19IL2 + L19TNFExperimentalOne arm, intratumoral injections of 10 Mio IU of L19IL2 and 312 μg L19TNF. Weekly administration for all combined leasions
Receives: Drug: L19IL2+L19TNF

What is being measured

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

  1. Rate of patients with complete response (CR) of L19IL2 treated Index/Non-Index lesions at week 12.

    Measured: Week 12

Secondary outcomes (3)

  1. Efficacy of L19IL2/L19TNF treated Index/non treated lesions

    • Rate of patients with CR, PR and SD of all metastases at week 12, 24 and 36 (objective response rate according to RECIST v 1.1)
    • Duration of objective response and disease control of all metastases
    • Median overall survival (mOS)

    Measured: week 12, 24 and 36

  2. Overall survival (OS)

    Measured: 1 year

  3. Safety of the combination treatment with L19IL2 and L19TNF

    Evaluation of the type and the number of adverse events eventually present

    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 posted3 Mar 2014 (estimated)
  2. Study startDec 2012
  3. Primary completionMay 2015
  4. Study completionMay 2015

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
21 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02076633
Sponsor's protocol ID
PH-L19IL2TNF-02/12
Status last verified
Oct 2014
First submitted
24 Feb 2014
Last updated
27 May 2015
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing L19IL2+L19TNF in people with Malignant Melanoma, Skin, run by Philogen S.p.A. at 2 sites in Italy.

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 17 inclusion and 16 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 27 May 2015. 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 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 phase mean?

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?

Rate of patients with complete response (CR) of L19IL2 treated Index/Non-Index lesions at week 12. (time frame: Week 12). 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 NCT02076633.

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 27 May 2015.

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