E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Merkel cell carcinoma (primary small cell carcinoma of the skin) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10064025 |
E.1.2 | Term | Merkel cell carcinoma |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
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. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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.
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E.4 | Principal 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.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of this study is overall survival rate at 12 months. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | 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. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
(1) 24 weeks (2) 12 months |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 7 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 30 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 30 |