Malignant Melanoma, Skin Clinical Trial
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
| Verified date | October 2014 |
| Source | Philogen S.p.A. |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | Italy: Ethics Committee |
| Study type | Interventional |
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.
| Status | Completed |
| Enrollment | 21 |
| Est. completion date | May 2015 |
| Est. primary completion date | May 2015 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | 18 Years and older |
| Eligibility |
Inclusion Criteria: - 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. - Able to provide written Informed Consent - Willingness and ability to comply with the scheduled visits, treatment plan, laboratory tests and other study procedures. Exclusion Criteria: - 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. - 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. |
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
| Country | Name | City | State |
|---|---|---|---|
| Italy | Fondazione IRCCS Istituto Nazionale dei Tumori | Milan | |
| Italy | Azienda Ospedaliera Universitaria Senese | Siena |
| Lead Sponsor | Collaborator |
|---|---|
| Philogen S.p.A. |
Italy,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Rate of patients with complete response (CR) of L19IL2 treated Index/Non-Index lesions at week 12. | Week 12 | No | |
| Secondary | 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) |
week 12, 24 and 36 | No |
| Secondary | Overall survival (OS) | 1 year | No | |
| Secondary | Safety of the combination treatment with L19IL2 and L19TNF | Evaluation of the type and the number of adverse events eventually present | 1 year | Yes |