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.

• Register: EUCTR
• Last refreshed on: 28 December 2015
• Main ID: EUCTR2012-001991-13-IT
• Date of registration: 26/07/2012
• Prospective Registration: Yes
• Primary sponsor: PHILOGEN S.P.A.
• Public 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.
• Scientific 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. - Intratumoral administration of L19IL2/L19TNF
• Date of first enrolment: 21/09/2012
• Target sample size: 20
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-001991-13
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: yes Other trial design description: uncontrolled, multicenter, prospective study If controlled, specify comparator, Other Medicinial Product: Placebo: Other: Number of treatment arms in the trial: 1

Countries of recruitment

Italy

Contacts

• Name: NA
• Affiliation: Philogen S.p.A.

• Name: NA
• Affiliation: Philogen S.p.A.

Key inclusion & exclusion criteria

Inclusion criteria:
1)Histologically confirmed malignant melanoma of the skin in clinical stage III or stage IV M1a 2)Presence of measurable and injectable cutaneous and/or subcutaneous lesions 3)Males or females, age >/= 18 years 4)ECOG/WHO performance status 1.5 x 10^9/L 7)Hemoglobin > 9.0 g/dL 8)Platelets > 100 x 10^9/L 9)Total bilirubin Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 10
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion criteria:
1) Uveal melanoma and mucosal melanoma 2)Evidence of visceral metastases and/or active brain metastases at screening 3)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 4)History of HIV infection or infectious hepatitis B or C 5)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. 6)History within the last year of acute or subacute coronary syndromes including myocardial infarction, unstable or severe stable angina pectoris. 7)Inadequately controlled cardiac arrhythmias including atrial fibrillation 8)Heart insufficiency (> Grade II, New York Heart Association (NYHA) criteria) 9)Uncontrolled hypertension 10)Ischemic peripheral vascular disease (Grade IIb-IV) 11)Severe diabetic retinopathy 12)Active autoimmune disease 13)History of organ allograft or stem cell transplantation 14)Recovery from major trauma including surgery within 4 weeks prior to administration of study treatment. 15)Known history of allergy to IL2, TNF, or other human proteins/peptides/antibodies. 16)Breast feeding female 17)Anti-tumor therapy within 4 weeks of the administration of study treatment (except small surgery). 18)Previous in vivo exposure to monoclonal antibodies for biological therapy in the 6 weeks before administration of study treatment. 19)Planned administration of growth factors or immunomodulatory agents within 7 days before the administration of study treatment 20)Patients in need of systemic treatment for rapidly progressive systemic disease. 21)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. oAny conditions that in the opinion of the investigator could hamper compliance with the study protocol.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

Histologically-confirmed malignant melanoma of the skin with presence of injectable cutaneous and/or subcutaneous lesions either in clinical stage III or stage IV M1a.
MedDRA version: 14.1 Level: PT Classification code 10025671 Term: Malignant melanoma stage IV System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 14.1 Level: PT Classification code 10025670 Term: Malignant melanoma stage III System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Intervention(s)

Product Name: tumor-targeting human L19TNFalpha monoclonal antibody-cytokinbe fusion protein
Product Code: L19TNFalfa
Pharmaceutical Form: Concentrate for solution for injection
Current Sponsor code: L19TNFa
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 208-

Product Name: tumor-targeting human L19IL2 monoclonal antibody-cytokine fusion protein
Product Code: L19IL2
Pharmaceutical Form: Solution for injection
Current Sponsor code: L19IL2
Concentration unit: million IU million international units
Concentration type: equal
Concentration number: 13-

Primary Outcome(s)

Primary end point(s): Rate of patients with complete response (CR) of L19IL2/L19TNF- treated lesions at week 12 (day 85)

Secondary Objective: Efficacy of L19IL2/L19TNF-treated lesions: 1)Objective response rate (Complete response CR and partial response PR) and disease control rate ( stable disease SD ) of L19IL2/L19TNF-treated lesions at week 12. Duration of objective response and disease control of L19IL2/L19TNF-treated lesions Efficacy of L19IL2/L19TNF- treated/non treated lesions: 2)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) 3) Duration of objective response and disease control of all metastases 4) Median overall survival (mOS). Safety of intratumoral administration of L19IL2/L19TNF.

Main Objective: Efficacy of L19IL2/L19TNF-treated lesions measured as : Rate of patients with complete response (CR) of L19IL2/L19TNF-treated lesions at week 12 (day 85).

Timepoint(s) of evaluation of this end point: Week 12 (85 days from treatment start)

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: from 12 weeks until 1 year

Secondary end point(s): oObjective response rate (Complete response CR and partial response PR) and disease control rate ( stable disease SD ) of L19IL2/L19TNF-treated lesions at week 12. Duration of objective response and disease control of L19IL2/L19TNF-treated lesions. oRate 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) oDuration of objective response and disease control of all metastases oMedian overall survival (mOS) Safety of intratumoral administration of L19IL2/L19TNF.

Secondary ID(s)

PH-L19IL2TNF-02/12

Source(s) of Monetary Support

Philogen S.P.A.