E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Stage IV Non-Small Cell Lung Cancer |
nemalobunkový karcinóm pľúc v štádiu IV |
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E.1.1.1 | Medical condition in easily understood language |
Metastatic lung cancer |
Metastatický zhubný nádor pľúc |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10025070 |
E.1.2 | Term | Lung carcinoma cell type unspecified stage IV |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To compare efficacy of DCVAC/LuCa + chemotherapy without immune enhancers vs. chemotherapy alone in patients with stage IV NSCLC, as measured by overall survival (OS). |
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E.2.2 | Secondary objectives of the trial |
• Comparison of PFS in patients treated with DCVAC/LuCa + chemotherapy without immune enhancers vs. chemotherapy alone. • Comparison of safety in patients treated with DCVAC/LuCa + chemotherapy without immune enhancers vs. chemotherapy alone. • Further comparison of efficacy of DCVAC/LuCa + chemotherapy without immune enhancers vs. chemotherapy alone, as measured by objective response rate (ORR) and duration of response (per RECIST 1.1). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1 Histologically or cytologically confirmed non-small cell lung cancer (NSCLC) of either adenomatous, squamous or large cell carcinoma differentiation; mixed tumors will be categorized by the predominant cell type. 2 Advanced NSCLC (stage IV unresectable disease) 3 Patients must have measurable or non-measurable disease 4 Patients (male and female) ≥ 18 years 5 Eastern Cooperative Oncology Group (ECOG) Performance status 0-1 6 Patients must have recovered from toxicity of any prior therapy (e.g. surgery, radiotherapy, or therapy for other diseases than NSCLC). Recovery is defined as less than or equal to grade 2 toxicity according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) (except alopecia) 7 Laboratory criteria 7.1 Platelet count of at least 100,000/mm3 (100 x 109/L) 7.2 White blood cells (WBC) greater than 4,000/mm3 (4.0 x109/L) 7.3 Hemoglobin (Hb) at least 9g/dL (90 g/L) 7.4 Total bilirubin levels ≤1.5mg/dL (benign hereditary hyperbilirubinemias, e.g., Gilbert´s syndrome are permitted) 7.5 Serum alanine aminotransferase and aspartate aminotransferase ≤ 5 times the upper limit of normal (ULN) 7.6 Serum creatinine ≤ 1.5 times the upper limit of normal (ULN) 8 Women of childbearing potential and sexually active males must agree to use an accepted and effective method of contraception (hormonal or barrier methods, abstinence) prior to study entry and for the duration of the treatment plus 3 months. 9 Signed informed consent including patient’s ability to comprehend its contents. (Consent to genetic testing is not a condition for participation in the clinical trial) |
1. Histologicky alebo cytologicky potvrdený nemalobunkový karcinóm pľúc (NSCLC) buď adenomatóznej, alebo skvamóznej diferenciácie; zmiešané nádory budú kategorizované podľa prevažujúceho typu buniek. 2. Pokročilý NSCLC (v štádiu IV, inoperabilný) 3. Pacienti musia mať merateľné alebo nemerateľné ochorenie 4. Pacienti (muži a ženy) vo veku ≥ 18 rokov 5. Stav telesnej výkonnosti posudzovaný podľa škály Eastern Cooperative Oncology Group (ECOG) 0–1 6. Laboratórne kritériá 6.1 Počet trombocytov aspoň 100 000/mm3 (100 × 109/l) 6.2 Počet leukocytov viac než 4 000/mm3 (4,0 × 109/l) 6.3 Hemoglobín aspoň 9 g/dl (90 g/l) 6.4 Hladina celkového bilirubínu ≤ 1,5 mg/dl (25 μmol/l) (benígna hereditárna hyperbilirubinémia, napr. Gilbertov syndróm, sú povolené) 6.5 Sérová alanínaminotransferáza (ALT) a aspartátaminotransferáza (AST) ≤ päťnásobok hornej hranice normy 6.6 Sérový kreatinín ≤ 1,5-krát vyšší než horná hranica normy 7. Ženy v reprodukčnom veku a sexuálne aktívni muži musia súhlasiť s užívaním akceptovanej a účinnej antikoncepčnej metódy (hormonálne alebo bariérové metódy, sexuálna abstinencia) pred vstupom do štúdie a po celý čas liečby a v nasledujúcich 3 mesiacoch. 8. Podpísaný informovaný súhlas vrátane stanoviska, že pacient je schopný porozumieť jeho obsahu. (Pre účasť v tomto klinickom skúšaní nie je súhlas s genetickými testami podmienkou.)
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E.4 | Principal exclusion criteria |
1 Prior chemotherapy for stage IV NSCLC 2 Immunotherapy, monoclonal antibodies received within 4 weeks prior to randomization 3 Patients comorbidities 3.1 Patients who are not indicated for chemotherapy treatment with first line Standard of Care chemotherapy (carboplatin/paclitaxel) 3.2 Active other malignancy than NSCLC 3.3 Known central nervous system (CNS) metastases 3.4 Any disease requiring chronic steroid or immunosuppressive therapy 3.5 HIV positive 3.6 Active hepatitis B (HBV) and/or C (HCV), active syphilis 3.7 Ongoing/active significant infection or other severe medical condition 3.8 Pre-existing thyroid disease unless it can be controlled with conventional treatment 3.9 Clinically significant cardiovascular disease including: 3.9.1 Uncontrolled congestive heart failure 3.9.2 Unstable angina pectoris 3.9.3 Uncontrolled severe cardiac arrhythmia 3.9.4 Myocardial infarction within 6 months prior randomization 3.10 Psychiatric illness/social situations that would limit compliance with study requirements 4 Pregnant or breast feeding women 5 Use of any experimental therapy within the last 4 weeks prior to randomization 6 Contra indications to treatment with hydroxychloroquine, known G6PD deficiency (anamnestic information, no test necessary) and psoriasis |
1. Predchádzajúca chemoterapia pre NSCLC v štádiu IV 2. Imunoterapia, liečba monoklonálnymi protilátkami počas posledných 4 týždňov pred randomizáciou 3. Komorbidity 3.1 Pacienti, ktorí neboli indikovaní na štandardnú chemoterapeutickú liečbu v prvej línii (karboplatina/paklitaxel) 3.2 Iné malígne ochorenia než NSCLC 3.3 Známe metastázy do centrálneho nervového systému 3.4 Akékoľvek ochorenie vyžadujúce chronickú liečbu steroidmi alebo imunosupresívami 3.5 HIV pozitívny pacient 3.6 Aktívna hepatitída B (HBV) a/alebo C (HCV), aktívny syfilis 3.7 Prebiehajúca/aktívna závažná infekcia alebo iný závažný zdravotný stav 3.8 Preexistujúce ochorenie štítnej žľazy, ktoré nie je možné kontrolovať konvenčnými liečebnými metódami 3.9 Klinicky signifikantné kardiovaskulárne ochorenie, ku ktorým sa radia: 3.9.1 neliečené kongestívne zlyhanie srdca, 3.9.2 nestabilná angina pectoris, 3.9.3 nekontrolovaná ťažká srdcová arytmia, 3.9.4 infarkt myokardu počas posledných 6 mesiacov pred randomizáciou. 3.10 Psychiatrické ochorenie/sociálna situácia, ktorá by limitovala compliance pacienta s požiadavkami štúdie 4. Tehotné alebo dojčiace ženy 5. Podanie experimentálnej liečby počas posledných 4 týždňov pred randomizáciou 6. Kontraindikácie liečby hydroxychlorochinom, známa deficiencia G6PD (anamnestický údaj, nie sú potrebné žiadne vyšetrenia) a psoriáza
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E.5 End points |
E.5.1 | Primary end point(s) |
OS defined as the time from the date of randomization to the date of death due to any cause. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary efficacy analysis will be performed approximately 12 months after the last patient randomization. |
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E.5.2 | Secondary end point(s) |
PFS Safety parameters as AEs, SAEs, laboratory abnormalities, vital signs ORR and duration of response (per RECIST 1.1)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The primary efficacy analysis will be performed approximately 12 months after the last patient randomization. |
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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 | No |
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) | Yes |
E.7.1.1 | First administration to humans | Yes |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Štandardná chemoterapia prvej línie karboplatinou a paklitaxelom |
Standard first line chemotherapy with carboplatin and paclitaxel |
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E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 12 |
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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End of the trial is 5 years after randomization of the last patient |
Štúdia bude ukončená 5 rokov po zaradení posledného pacienta |
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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 | 7 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 7 |