E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced Renal Cell Carcinoma |
Metastatisk Nyrecancer |
|
E.1.1.1 | Medical condition in easily understood language |
Renal Cell Carcinoma |
Nyrekræft |
|
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 | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10038409 |
E.1.2 | Term | Renal cell carcinoma NOS |
E.1.2 | System Organ Class | 100000004864 |
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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 evaluate toxicity (according to CTCAE version 4.0) and feasibility. |
At evaluere bivirkninger (ifølge CTCAE version 4.0) og gennemførlighed. |
|
E.2.2 | Secondary objectives of the trial |
To evaluate treatment related immune responses To evaluate clinical response (according to RECIST 1.1 - response rate, progressionfree survival and overall survival) |
At evaluere behandlingsrelateret immunresponser At evaluere klinisk respons (ifølge RECIST 1.1 - responsrate, progressionsfri overlevelse og samlet overlevelse) |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Histological proven mRCC with the possibility of surgical removal of tumor tissue of > 1 cm3. Histology must include a clear cell component with or without a sarcomatoid dedifferentiation. 2. Metastatic disease irrespective of number of previous treatment lines. Treatment naïve pt’s can be included. 3. Age: 18 – 70 years. 4. ECOG performance status of ≤1. 5. IMDC prognostic group ‘Favorable’ or ‘Intermediary’ 6. Life expectancy of > 6 months. 7. At least one measurable parameter after surgery in accordance with RECIST 1.1 –criteria’s. 8. No significant toxicities or side effects (CTC ≤ 1) from previous treatments. 9. Normal ejection fraction (EF) measured by a multigated acquisition (MUGA) scan. 10. Crom EDTA clearance >40 ml/min 11. Sufficient organ function. 12. LDH ≤ 5 times upper normal limit as a measure of tumor burden 13. Women in the fertile age must use effective contraception. Likewise, men included in the study, as well as their partners, must use effective contraception. This applies from inclusion and until 6 months after treatment. Birth control pills, spiral, depot injection with gestagen, subdermal implantation, hormonal vaginal ring and transdermal depot patch are all considered safe contraceptives. 14. Signed statement of consent after receiving oral and written study information. The subject may also provide consent for Future Biomedical Research. However, the subject may participate in the main trial without participating in Future Biomedical Research 15. Willingness to participate in the planned controls. |
1. Histologisk verificeret metastatisk RCC med mulighed for kirurgisk fjernelse af tumorvæv på > 1 cm3. Histologien skal indeholde en clear celle komponent med eller uden sarkomatoid dedifferentiering. 2. Metastatisk sygdom uanset antallet af tidligere behandlinger. Behandlingsnaive patienter kan inkluderes. 3. Alder 18-70 år. 4. ECOG performance status < 1. 5. IMDC prognostisk gruppe 'Favorabel' eller 'Intermediær'. 6. Forventet levetid > 6 måneder. 7. Mindst et målbart parameter efter kirurgi i henhold til RECIST 1.1 kriterierne. 8. Ingen signifikant toxicitet eller bivirkninger (CTC ≤ 1) fra tidligere behandlinger. 9. Normal uddrivelsesfraktion (EF) målt ved MUGA 10. Crom EDTA clearance >40 ml/min 11. Sufficient organ funktion. 12. LDH ≤ 5 gange over øvre normalgrænse som mål for tumorbyrde. 13. Kvinder i den fertile alder skal benytte sikker antikonception. Det samme skal mænd og deres partnere. Dette gælder fra inklusion til 6 måneder efter behandlingen. 14. Underskrevet samtykke efter mundtlig og skriftlig forsøgsinformation. 15. Patienten skal være villig til at deltage i de planlagte kontroller og i stand til at håndtere toxicitet. |
|
E.4 | Principal exclusion criteria |
1. A history of prior malignancies, exept curatively treated non-melanoma skin cancer and CIS of the cervix uteri. Patients treated for another malignancy can participate if they are without signs of disease for a minimum of 3 years after treatment. 2. Patients with cerebral metastases. 3. Patients with widespread bone or bone only metastases. 4. Known hypersensitivity to one of the active drugs or one or more of the excipients. 5. Severe medical conditions, such as severe asthma/COLD, ischemic hearth disease/significant cardiac disease (e.g. NYHA class ≥2), poorly regulated insulin dependent diabetes mellitus among others, which can interfere with patient compliance and/or significantly increase the risk of side effects upon investigators clinical judgement. 6. Acutte/chronic infection with HIV, hepatitis, tuberculosis among others. 7. Severe allergies or previous anaphylactic reactions. 8. Active autoimmune disease, such as autoimmune neutropenia/thrombocytopenia or hemolytic anemia, systemic lupus erythematosis, Sjögren’s syndrome, sclerodermia, myasthenia gravis, Goodpasteur’s disease, Addison’s disease, Hashimotos thyroiditis, active Graves disease. 9. Pregnant women and women breastfeeding. 10. Simultaneous treatment with systemic immunosuppressive drugs (including prednisolone, methotrexate among others). 11. Simultaneous treatment with other experimental drugs. 12. Simultaneous treatment with other systemic anti-cancer treatments. 13. Patients with active and uncontrollable hypercalcaemia. |
1. Tidligere cancer undtagen kurativt behandlet ikke-melanom hudkræft og CIS i cervix uteri. 2. Patienter med cerebrale metastaser. 3. Patienter med udbredte knoglemetastaser eller kun knoglemetastaser. 4. Kendt hypersensitivitet til et af de aktive stoffer eller en/flere af hjælpestofferne. 5. Alvorlig komorbiditet, som eksempelvis svær astma/KOLD, iskæmisk hjertesygdom/signifikant hjertesygdom, dårligt reguleret insulin-afhængig sukkersyge, som kan påvirke patient compliance og/eller signifikant øge risikoen for bivirkninger efter investigators kliniske vurdering. 6. Akut/kronisk infektion med HIV, hepatitis, tuberkulose blandt andre. 7. Alvorlige allergier eller tidligere anafylaktiske reaktioner. 8. Aktiv autoimmun sygdom, eksempelvis autoimmun neutropeni/trombocytopeni eller hæmolytisk anæmi, lupus erythematosis, sjögrens syndrom, sclerodermi, myasthenia gravis, Goodpasteur’s sygdom, Addison’s sygdom, Hashimotos thyroiditis, aktiv Graves sygdom. 9. Gravide kvinder og kvinder der ammer. 10. Samtidig behandling med systemiske immunsupprimerende stoffer (herunder prednisolon, methotrexat blandt andre). 11. Samtidig behandling med andre eksperimentelle stoffer. 12. Samtidig behandling med andre systemiske anti-cancer behandlinger. 13. Patienter med aktiv og ukontrollerbar hypercalcæmi. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is toxicity (according to CTCAE 4.0). |
Det primære endepunkt er bivirkninger (ifølge CTCAE 4.0). |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary endpoint will be evaluated before treatment, during treatment and at follow-up visits untill 6 months after treatment. |
Det primære endepunkt vil blive evalueret før behandling, under behandling og ved opfølgende besøg op til 6 måneder efter behandling. |
|
E.5.2 | Secondary end point(s) |
Secondary endpoints are treatment related immune response and clinical response (according to RECIST 1.1 - response rate, progressionfree survival and overall survival). |
Sekundære endepunkter er behandlingsrelateret immunrespons og klinisk respons (ifølge RECIST 1.1 - responsrate, progressionsfri overlevelse og samlet overlevelse). |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
The secondary endpoints will be evaluated after all patients have received treatment and clinical response is evaluated. Estimated 1 year after treatment of last patient. |
De sekundære endepunkter vil blive evalueret efter at alle patienter har modtaget behandling og klinisk respons er vurderet. Estimeret 1 år efter sidste patients behandling. |
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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 | No |
E.8.1.1 | Randomised | No |
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 | No |
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 | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
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
|
LVLS |
Sidste patients sidste besøg |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
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 | 3 |