Overview

This trial is active, not recruiting.

Condition metastatic melanoma stage iv
Treatments l19il2 - ph i, l19il2 at rd - ph ii, dtic
Phase phase 1/phase 2
Sponsor Philogen S.p.A.
Start date October 2013
End date April 2017
Trial size 96 participants
Trial identifier NCT02076646, PH-L19IL2DTIC-04-12

Summary

A prospective, open-label, multi-center, Phase I/II study of L19IL2 in combination with Dacarbazine in patients with metastatic melanoma.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Cohorts of 3-6 patients will receive escalating doses of L19-IL2 until MTD is reached. L19-IL2 will be administered on days 1, 8 & 15 of each 21-day-cycle. Dacarbazine will be given at a fixed dose on day 1 of each 21-day cycle, 30 minutes after the end of the L19-IL2 infusion.
l19il2 - ph i
During phase I part of the study, increasing dose of L19IL2 from one cohort to the next will be performed in steps of 160,000 IU/kg starting at 480,000 IU/kg (i.e., 0.48; 0.64; 0.80 MioIU/kg until MTD is reached).
dtic DETICENE®
Dacarbazine: 1 hour intravenous infusion on day 1 of each 21-cycle at a dosage of 1000 mg/m2 (fixed dose).
(Experimental)
During the phase II part of this study, 60 patients with Stage IV M1a and M1b melanoma will be randomized in a 1:1 ratio: 30 patients assigned to Arm 1 will receive L19IL2 at the RD + DTIC at a fixed dose.
l19il2 at rd - ph ii
L19IL2 at RD will be administered to Arm 1 patients during phase II part of the study.
dtic DETICENE®
Dacarbazine: 1 hour intravenous infusion on day 1 of each 21-cycle at a dosage of 1000 mg/m2 (fixed dose).
(Active Comparator)
During the phase II part of this study, 60 patients with Stage IV M1a and M1b melanoma will be randomized in a 1:1 ratio: 30 patients assigned to Arm 2 will receive DTIC at a fixed dose as monotherapy.
dtic DETICENE®
Dacarbazine: 1 hour intravenous infusion on day 1 of each 21-cycle at a dosage of 1000 mg/m2 (fixed dose).

Primary Outcomes

Measure
Phase I: maximum tolerated dose (MTD) and recommended dose (RD) of L19IL2
time frame: From day 1 to day 21 of Cycle 1 (each cycle is 21-days)
Phase II: best objective response rate (BORR)
time frame: Up to 1 year

Secondary Outcomes

Measure
Phase I: best objective response rate (BORR)
time frame: Up to 1 year
Phase I: duration of objective response
time frame: From week 6 up to 1 year
Phase I: disease control rate
time frame: At 6 months
Phase I: median progression free survival (mPFS)
time frame: Up to 1 year
Phase I: median overall survival and overall survival rate
time frame: Up to 1 year
Phase II: safety and tolerability of L19-IL2 in combination with DTIC vs DTIC alone.
time frame: Up to 1 year
Phase II: duration of objective response
time frame: Up to 1 year
Phase II: disease control rate
time frame: At 6 months
Phase II: median progression free survival (mPFS)
time frame: Up to 1 year
Phase II: median overall survival and overall survival rate
time frame: Up to 1 year

Eligibility Criteria

Male or female participants from 18 years up to 70 years old.

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., IFN, 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. 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.or allogeneic peripheral blood progenitor cell or bone marrow transplantation 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). 26. Melanoma patients with BRAF 600 E mutation who are amenable to receive approved treatments able to extend overall survival.

Additional Information

Official title A Phase I/II Dose Escalation Study of the Tumor-targeting Human L19-IL2 Monoclonal Antibody-cytokine Fusion Protein in Combination With Dacarbazine for Patients With Metastatic Melanoma
Principal investigator Claus Garbe, Prof. M.D.
Description A prospective, open-label, multi-center, Phase I/II dose escalation study in which cohorts of 3-6 patients with metastatic melanoma will be assigned to receive escalating doses of L19-IL2 in combination with a fixed dose of Dacarbazine. After definition of MTD and RD during the phase II part of this study, 60 patients with Stage IV M1a and M1b melanoma will be randomized in a 1:1 ratio to receive open label the combination treatment at the RD (Arm 1) or DTIC monotherapy (Arm 2).
Trial information was received from ClinicalTrials.gov and was last updated in October 2016.
Information provided to ClinicalTrials.gov by Philogen S.p.A..