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About
This Phase II clinical study is an open-label, multicenter study of L19IL2 in combination with Dacarbazine in patients with metastatic melanoma.
The study is divided in two parts: a phase IIa part, designed to establish the recommended dose (RD) of L19IL2 when administered in combination with a fixed dose of Dacarbazine, as well as to determine the preliminary tolerability profile; the second phase IIb part evaluates the objective response rate (ORR) including a randomized study with a fixed dose of Dacarbazine with or without L19IL2, dosed at the RD determined in phase IIa.
Full description
Dose limiting toxicity will be assessed during the dose-escalation part of Phase IIa from day 1 through day 21 of the first cycle.
Response will be measured using RECIST criteria every 6 weeks (after every 2 cycles of treatment). Patients with stable or responding disease at each assessment may receive additional treatment for a maximum of 6 cycles of induction. Patients with stable or responding disease after induction may receive L19IL2 (without dacarbazine) every 2 weeks as maintenance therapy.
Tumor expression of ED-B FN and tumor uptake of L19IL2 and of Dacarbazine will be assessed via immunohistochemistry and/or other methods deemed appropriate on tumor tissue biopsies. Tumor biopsy will be performed on superficial accessible cutaneous and/or subcutaneous lesions only. Tumor biopsy will be considered optional and will not preclude patient entry on to study should the patient refuse.
Pharmacokinetics of L19IL2, Dacarbazine and AIC will be assessed from serial blood samples using standard methods.
Overall response rate, PFS, survival rate at 6 and 12 months, and overall survival time for all patients and separately for the patients in the Phase IIb part will be assessed using standard methods.
Enrollment
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Inclusion criteria
Histologically or cytologically confirmed unresectable metastatic (stage IV) non-uveal melanoma
Age > 18 years
Measurable disease defined as at least one lesion that can be accurately and serially measured per the modified RECIST criteria. Cutaneous lesions measuring at least 1 cm will be considered measurable.
Prior therapy for metastatic melanoma:
Fewer than 3 organs involved or cutaneous and/or subcutaneous metastasis only, for PhaseIIb patients
ECOG performance status < 2
Life expectancy of at least 12 weeks
Absolute neutrophil count > 1.5 x 109/L, hemoglobin > 9.0 g/dL and platelets > 100 x 109/L
Total bilirubin ≤ 30 µmol/L (or ≤ 2.0 mg/Dl)
ALT and AST ≤ 2.5 x the upper limit of normal (5.0 x ULN for patients with hepatic involvement with tumor
LDH < 2.0 x ULN for Phase IIa patients and normal LDH for the Phase IIb ones.
Serum creatinine < 1.5 x ULN
All toxic effects of prior therapy must have resolved to ≤ Grade 1 unless otherwise specified above
Negative serum pregnancy test (for women of child-bearing potential only) at screening
Exclusion criteria
Primary purpose
Allocation
Interventional model
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102 participants in 3 patient groups
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Data sourced from clinicaltrials.gov
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