Metastatic Melanoma stage IV MedDRA version: 14.1 Level: LLT Classification code 10027481 Term: Metastatic melanoma System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Dacarbazin
Product Name: Dacarbazin
Pharmaceutical Form: Powder for solution for injection/infusion
Product Code: L19IL2
Pharmaceutical Form: Solution for infusion
Sponsors
Philogen S.p.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. 18-70 years of age, inclusive 2. Must have histologically or cytologically confirmed cutaneous metastatic melanoma (Stage IV). For the Phase II part only patients with Stage IV M1a or M1b will be enrolled. 3. Must have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) as identified by CT or MRI scan within 28 days before the first study drug administration. 4. Baseline LDH within normal range. 5. Maximal 1 line of previous systemic treatment for metastatic disease (prior adjuvant melanoma therapy, e.g., IFNa, is permitted. 6. For women of childbearing potential, a negative pregnancy test within 72 hours prior to the first dose of study treatment. 7. Women with reproductive potential must be willing to practice acceptable methods of birth control during the study and for up to 12 weeks after the last dose of study medication. 8. Men with reproductive potential must be willing to practice acceptable methods of birth control during the study and for up to 12 weeks after the last dose of study medication. 9. Must have Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1. 10. Life expectancy of at least three months. 11. Adequate organ function: serum creatinine = 1.5 x ULN, total bilirubin = 30 mM/L (or mg/dL, = 2.0 mg/dL), hepatic transaminases = 2.5 x ULN, alkaline phosphatase = 2.5 x ULN. 12. ANC count = 1.5 x 10^9/L, platelet count = 100 x 10 ^9/L, hemoglobin > 9 g/dL. 13. Normal 12-lead ECG and normal bidimensional echocardiogram or MUGA. 14. All toxic effects of prior therapy must have resolved to grade =1 unless otherwise specified above. 15. Willing and able to give written informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 70 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 26
Exclusion criteria
Exclusion criteria: 1. Pregnant or breastfeeding female 2. Primary ocular melanoma 3. Primary mucosal melanoma 4. Use of any investigational or other anti-cancer drug within 28 days or 5 half-lives, whichever is longer, preceding the first dose of DTIC and L19-IL2. 5. Prior radiation to a target lesion, unless there has been clear progression of the lesion since radiotherapy. 6. A history of known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) infection. 7. History or clinical evidence of brain metastases or leptomeningeal disease. 8. Any other malignancy from which the patient has been disease-free for less than 5 years, with the exception of adequately treated and cured basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix. 9. Treatment with DTIC within 6 months before start of study. 10. Treatment with Ipilimumab within 6 months before start of study. 11. Hypersensitivity to DTIC 12. Concomitant use of drugs known to alter cardiac conduction 13. Chronic use of corticosteroids used in the management of cancer or non-cancer-related illness. 14. Unstable or serious concurrent uncontrolled medical conditions. 15. Inadequately controlled cardiac arrhythmias including atrial fibrillation. 16. History of acute or subacute coronary syndromes including myocardial infarction, unstable or severe stable angina pectoris. 17. Heart insufficiency > grade II NYHA criteria. 18. Uncontrolled hypertension 19. Ischemic peripheral vascular disease. 20. Active infection or incomplete wound healing. 21. History or evidence of active autoimmune disease. 22. Known history of allergy to intravenously administered proteins/peptides/antibodies. 23. History of organ allograft. 24. Major trauma including surgery within 4 weeks prior to entering the study. 25. Any underlying medical or psychiatric condition which in the opinion of the investigator will make administration of study drug hazardous or hinder the interpretation of study results (e.g., AE).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase I: Maximum tolerated dose (MTD) and the recommended dose (RD) of L19IL2 for phase II when administered in combination with a fixed dose of DTIC. Phase II: Antitumor activity in terms of best objective response rate (BORR) in patients treated with L19-IL2 at RD in combination with DTIC versus patients treated with DTIC monotherapy. ;Secondary Objective: For Phase I: •Antitumor activity in terms of confirmed best objective response rate (BORR), duration of overall response, disease control rate, progression free survival (PFS) and overall survival (OS). For Phase II: •Safety and Tolerability of L19-IL2 in combination with DTIC vs DTIC alone. •Duration of overall response, as well as disease control rate, progression free survival (PFS) and overall survival (OS). ;Primary end point(s): Phase I • Safety evaluation performed on days 1 through 21 including AEs, SAE and standard laboratory assessment will be used for determination of dose limiting toxicity (DLT). Phase II for both arms • Best objective response rate (BORR), which is defined as the rate of patients with Complete Response (CR) or Partial Response (PR) (defined according to RECIST 1.1 ) from the start of the study treatment until the end of the study. ;Timepoint(s) of evaluation of this end point: Phase I: day 1-21 Phase II: from the start of the study treatment until the end of the study. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Phase I 1) Confirmed best objective response rate (BORR), which is defined as the percentage of subjects with a confirmed complete response (CR) or partial response (PR) as per RECIST 1.1 criteria in patients treated with L19-IL2 in combination with DTIC 2) Duration of overall response according to RECIST 1.1 3) Disease control rate (CR + PR + SD) at 24 weeks 4) Median progression free survival (mPFS) defined as the time elapsed between treatment initiation and tumor progression or death from any cause, with censoring of patients who are lost to follow-up. 5) Median overall survival and Overall Survival rate at 1 year from treatment initiation until death due to any cause Phase II for both arms: 1) Safety evaluation including AEs, SAE and standard laboratory assessment 2) Duration of overall response according to RECIST 1.1 3) Disease control rate (CR + PR + SD) at 24 weeks 4) Median progression free survival (mPFS) defined as the time elapsed between treatment initiation and tumor progression or death from any cause, with censoring of patients who are lost to follow-up. 5) Median Overall survival and overall survival rate at 1 year from treatment initiation until death due to any cause ;Timepoint(s) of evaluation of this end point: Phase I: 1) from the start to the end of the study 2) from the start to the end of the study 3) at 24 weeks 4) from the start to the end of the study 5) at 1 year from treatment initiation Phase II: 1) from the start to the end of the study 2) from the start to the end of the study 3) at 24 weeks 4) from the start to the end of the study 5) at 1 year from treatment initiation | — |
Countries
Germany, Italy
Contacts
Public ContactRegulatory Affairs
Philogen S.p.A.
Outcome results
None listed