KURZPROTOKOLL Lipo-MERIT
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KURZPROTOKOLL Lipo-MERIT
KURZPROTOKOLL Lipo-MERIT Öffentlicher Titel Phase I Studie zum Impfstoff Lipo-MERIT bei Patienten mit fortgeschrittenem Melanom Wissenschaftl. Titel Clinical first-in-human dose escalation study evaluating the safety and tolerability of intravenous administration of a tetravalent RNA-lipoplex cancer vaccine targeting the tumor-associated antigens NY-ESO-1, tyrosinase, MAGE-A3, and TPTE in patients with advanced melanoma Kurztitel Lipo-MERIT Studienart multizentrisch, prospektiv, Therapiestudie, randomisiert, offen/unverblindet, einarmig Studienphase Phase I Erkrankung DERMA: Melanom: Zweitlinie oder höher Ziele - Number of Adverse Events as a Measure of safety and tolerability [ Time Frame: 90 days ] [ Designated as safety issue: Yes ] Number of patients with adverse events, total number of adverse events, dose limiting toxicities - Maximum Tolerated Dose (MTD) [ Time Frame: dose escalation phase, an average of 15 days per patient ] [ Designated as safety issue: Yes ] MTD for multiple dosing of Lipo-MERIT vaccine by assessment of patient data, adverse events and/or dose limiting toxicities (DLT) by the independent data safety monitoring board (DSMB) - Change of induced T-cell responses for Lipo-MERIT vaccine from visit 2 to 8 (assessed by immunoassays) [ Time Frame: 43 days ] [ Designated as safety issue: No ] vaccine induced T-cell responses assessed by immunoassays in peripheral blood and skin - Clinical Monitoring of tumour lesions (determined by CT or MRI results evaluated by irRC) [ Time Frame: 90days ] [ Designated as safety issue: No ] Tumour lesion status as determined by CT or MRI results evaluated by irRC - Cohort I: stage IV malignant melanoma (AJCC 2009 melanoma classification) - Cohorts II-VI (after DSMB release): stage IIC, IIIA-C, or stage IV of malignant melanoma (AJCC 2009 melanoma classification) - Therapy only for subjects not eligible or declining any other available approved therapy after all available treatment options have been transparently disclosed (to be documented!) Expression of either one of the selected TAA confirmed by RT-PCR analysis from FFPE - 18 years of age - Written informed consent - ECOG performance status (PS) 0-1 - Life expectancy > 6 months - WBC 3x109/L - Haemoglobin 10 g/dL - Platelet count 100,000/mm³ - LDH level < 2.0 x ULN - ALT/AST < 3 x ULN (except patients with liver metastasis) - Negative pregnancy test (measured by -HCG) for females with childbearing age - Pregnancy or breastfeeding - Primary ocular melanoma - Concurrence of a second malignancy other than squamous or basal cell carcinoma, non-active prostate cancer or cervical carcinoma in situ or non-active treated urothelial carcinoma - Brain metastases - Post-splenectomy patients - Known or symptomatic pleural effusions and/or ascites Einschlusskriterien Ausschlusskriterien © Universitäres Centrum für Tumorerkrankungen (UCT) am Universitätsklinikum Frankfurt Ohne Gewähr für Richtigkeit oder Vollständigkeit, www.uct-frankfurt.de Stand: 20.01.2017; Seite 1 von 2 KURZPROTOKOLL Lipo-MERIT - Known hypersensitivity to the active substance or to any of the excipients - A serious local infection (e. g. cellulitis, abscess) or systemic infection (e. g. pneumonia, septicemia) which requires systemic antibiotic treatment within 2 weeks prior to the first dose of study medication - Positive test for acute or chronic active hepatitis B or C infection, acute EBV, or acute CMV - Clinically relevant autoimmune disease - Systemic immune suppression: HIV disease; Use of chronic oral or systemic steroid medication (topical or inhalational steroids are permitted); Other clinical relevant systemic immune suppression - Symptomatic congestive heart failure (NYHA 3 or 4) - Unstable angina pectoris - Radiotherapy and minor surgery within 14 days prior to the first administration of study treatment - Myelosuppressive chemotherapy within 14 days and after reconstitution of blood values prior to the first administration of study treatment - Ipilimumab within 28 days prior to the first administration of study treatment - Interferon, major surgery,vaccination, and other investigational agents within 28 days or 5 half-life's depending on what gives the longer range before the first treatment - Approved BRAF inhibitors Vemurafenib or Dabrafenib as well as the approved MEK inhibitor Trametinib in patients of the dose escalation cohorts. Concomitant treatment with approved BRAF inhibitors or MEK inhibitor is allowed for patients included in one of the two expanded dose cohorts, after analysis of safety data collected for the dose escalation cohorts and DSMB approval.Local radiation will be allowed as concurrent treatment. - Fertile males and females who are unwilling to use a highly effective method of birth control (less than 1% per year, e.g. condom with spermicide, diaphragm with spermicide, birth control pills, injections, patches or intrauterine device) during study treatment and 28 days after the last dose of study treatment - Presence of a serious concurrent illness or other condition (e. g. psychological, family, sociological, or geographical circumstances) that does not permit adequate follow-up and compliance with the protocol Alter 18 Jahre und älter Status Aktiv Beginn der Rekrutierung 01.04.2016 Fallzahl 42 Prüfzentren Universitätsklinikum Frankfurt Klinik für Dermatologie, Venerologie und Allergologie Theodor-Stern-Kai 7 60590 Frankfurt am Main Dr. Vesselina Laubach Tel: 069 6301 6162 Fax: 069 6301 83175 [email protected] Sponsoren BioNTech AG Registrierung in anderen Studienregistern ClinicalTrials NCT02410733 EUDRACT 2013-001646-33 © Universitäres Centrum für Tumorerkrankungen (UCT) am Universitätsklinikum Frankfurt Ohne Gewähr für Richtigkeit oder Vollständigkeit, www.uct-frankfurt.de Stand: 20.01.2017; Seite 2 von 2