Intratumoral Administration of L19IL2/L19TNF

NCT02076633 | Completed Phase 2

• 1 other identifier: PH-L19IL2TNF-02/12
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 2

Brief 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. 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.

Conditions

Malignant Melanoma, Skin

Keywords

L19; monoclonal; antibody; IL-2; TNFα; Interleukin; Phase II; metastatic melanoma; clinical stage III; Clinical stage IV M1a

Outcome Measures

Primary Outcomes (1)

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

  Week 12

Secondary Outcomes (3)

• Efficacy of L19IL2/L19TNF treated Index/non treated lesions

  week 12, 24 and 36

• Overall survival (OS)

  1 year

• Safety of the combination treatment with L19IL2 and L19TNF

  1 year

Study Arms (1)

L19IL2 + L19TNF

EXPERIMENTAL

One arm, intratumoral injections of 10 Mio IU of L19IL2 and 312 μg L19TNF. Weekly administration for all combined leasions

Drug: L19IL2+L19TNF

Interventions

L19IL2+L19TNF DRUG

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

L19IL2 + L19TNF

Eligibility Criteria

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

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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
• 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.
• Any conditions that in the opinion of the investigator could hamper compliance with the study protocol.

Sponsors & Collaborators

• Philogen S.p.A.: lead

Study Sites (2)

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, Italy

Location

Azienda Ospedaliera Universitaria Senese

Siena, Italy

Location

MeSH Terms

Conditions

Melanoma

Interventions

daromun

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Mario Santinami, Dr

  Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 24, 2014
• First Posted: March 3, 2014
• Study Start: December 1, 2012
• Primary Completion: May 1, 2015
• Study Completion: May 1, 2015
• Last Updated: May 27, 2015

Record last verified: 2014-10

Locations

IT (2)