Merkel cell carcinoma MedDRA version: 14.1 Level: LLT Classification code 10064025 Term: Merkel cell carcinoma System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Paclitaxel
Product Name: Paclitaxel
Pharmaceutical Form: Concentrate for solution for infusion
Product Name: Interleukin-2 fused to the F16 single chain Fv antibody
Product Code: F16IL2
P
Sponsors
Philogen S.p.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •Patients with advanced or metastatic Merkel cell carcinoma (MCC) not amenable to surgery and who have not received previous systemic therapy with taxanes; diagnosis of MCC must be histologically confirmed (evaluation of primary lesions or advanced disease) and endorsed by the IMMOMEC central dermatopathology center (central review of diagnosis at the Department of General Dermatology, Medical University of Graz). Patients must be amenable for paclitaxel treatment according to the discretion of the principal investigator; • Patients aged >/= 18 = 75 years; • ECOG performance status = 1; • Patients must have measurable disease including cutaneous and subcutaneous metastases as defined by RECIST v.1.1 criteria [23] or immune related response Criteria (irRC) [24] as assessed by CT or MRI and/or ultrasound within 4 weeks before the first study drug administration. • All acute side effects from any prior therapy must have resolved to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (v4.03) Grade = 1;. • Adequate hematologic, liver and renal function: o Absolute neutrophil count (ANC) = 1.5 x 10^9/L, platelets = 100 x 10^9/L, haemoglobin (Hb) = 9.0 g/dl o Alkaline phosphatase (AP), alanine aminotransferase (ALT) and/or aspartate aminotransferase = 3 x upper limit of reference range (ULN), and total bilirubin = 2.0 mg/gL unless liver involvement by the tumor, in which case the transaminase levels could be = 5 x ULN o Creatinine = 1.5 ULN or 24 h creatinine clearance = 50 mL/min • Negative serum pregnancy test for females of childbearing potential within 14 days of starting treatment; • 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; • Evidence of a personally signed and dated EC-approved Informed Consent form indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the study; • Willingness and ability to comply with the scheduled visits, treatment plan, laboratory tests and other study procedures. 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 45 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 45
Exclusion criteria
Exclusion criteria: • Life expectancy of less than 3 months; • Any previous taxanes therapy; • Previous or concurrent CLL patients; • Any other malignancy from which the patient has been disease-free for less than 2 years prior to study entry, with the exception of adequately treated and cured cervical carcinoma in situ, basal or squamous cell carcinoma, superficial bladder cancer, or in situ melanoma; • Presence of uncontrolled infections or other severe concurrent disease, which, in the opinion of the investigator, would place the patient at undue risk or interfere with the study; • Presence of known brain metastases; • Chronic-active hepatitis B, C, or HIV; • Severe cardiovascular disease: o History of acute or subacute coronary syndromes including myocardial infarction, unstable or severe stable angina pectoris; o Heart insufficiency (> Grade II, New York Heart Association (NYHA) criteria); o Irreversible cardiac arrhythmias requiring permanent medication; o LVEF </= 50% and/or abnormalities observed during baseline 2D-ECHO or 12-lead ECG investigations; o Uncontrolled hypertension; o Ischemic peripheral vascular disease (Grade IIb-IV); • Severe rheumatoid arthritis; or other uncontrolled autoimmune disease; • Severe diabetic retinopathy; • History of allograft or stem cell transplantation; • Major trauma including major surgery (e.g. visceral surgery) within 4 weeks of administration of study treatment; • Known history of allergy to IL-2, taxanes, cremophor or other intravenously administered human proteins/peptides/antibodies; • Pregnancy or breast-feeding. Female patient must agree to use effective contraception, or be surgically sterile or postmenopausal. The definition of effective contraception will be based on the European guideline ICH M3 rev 2. • Treatment with an investigational study drug within four weeks before beginning of treatment with F16IL2; • Previous treatment with monoclonal antibodies for biological therapy in the four weeks before administration of study treatment; • Any conditions that in the opinion of the investigator could hamper compliance with the study protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the efficacy of F16IL2 in combination with paclitaxel vs. paclitaxel monotherapy, in terms of overall survival rate at 12 months after beginning of study treatments, in patients with metastatic Merkel cell carcinoma, who are not amenable to surgery.;Secondary Objective: To investigate safety and tolerability of the combination treatment of F16IL2 and paclitaxel. To investigate the treatment efficacy in terms of response to treatment measured as ORR and DCR. ;Primary end point(s): The primary endpoint of this study is overall survival rate at 12 months.;Timepoint(s) of evaluation of this end point: 12 months. | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: (1) 24 weeks (2) 12 months;Secondary end point(s): The secondary endpoints of this study are (1) safety and tolerability assessment of the combination treatment of F16IL2 and paclitaxel in terms of adverse events, clinical laboratory evaluations, vital signs and physical examinations(2) treatment efficacy evaluation in terms of response to treatment measured as ORR and DCR. | — |
Countries
Austria, Denmark, France, Germany, Poland, Spain, United Kingdom
Contacts
Public ContactRegulatory Affairs
Philogen S.p.A.
Outcome results
None listed