E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced Ovarian-, Fallopian Tube- and Primary Peritoneal Cancer. |
Metastatisk ovarie-, tuba og primær peritoneal cancer. |
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E.1.1.1 | Medical condition in easily understood language |
Ovarian Cancer, Fallopian Tube Cancer and Primary Peritoneal Cancer. |
Æggestokkekræft, æggelederkræft og primær bughindekræft. |
|
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 | 10033130 |
E.1.2 | Term | Ovarian cancer NOS |
E.1.2 | System Organ Class | 100000004864 |
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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 | 10016183 |
E.1.2 | Term | Fallopian tube cancer NOS |
E.1.2 | System Organ Class | 100000004864 |
|
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 | 10052171 |
E.1.2 | Term | Peritoneal carcinoma |
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 advanced ovarian-, fallopian tube or primary peritoneal cancer with the possibility of surgical removal of tumor tissue of > 1 cm3. All histologies can be included. 2. Progressive or recurrent resistant disease after platin-based chemotherapy (platinum resistant) or progressive or recurrent disease after second line or additional chemotherapy. 3. Age: 18 – 70 years. 4. ECOG performance status of ≤1. 5. Life expectancy of > 6 months. 6. At least one measurable parameter in accordance with RECIST 1.1 –criteria’s. 7. No significant toxicities or side effects (CTC ≤ 1) from previous treatments, except sensoric- and motoric neuropathy (CTC ≤ 2) and/or alopecia (CTC ≤ 2). 8. Sufficient organ functions. 9. Women in the fertile age 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. 10. Signed statement of consent after receiving oral and written study information 11. Willingness to participate in the planned controls and capable of handling toxicities. |
1. Histologisk verificeret metastatisk ovarie-, tuba- eller primær peritoneal cancer, hvor det er muligt kirurgisk at fjerne minimum 1 cm3 tumorvæv. Alle histologier kan inkluderes. 2. Progression/genkomst af cancersygdommen efter platin-baseret kemoterapi (platin-resistent) eller progression/genkomst efter 2. linje eller yderligere behandling. 3. Alder: 18 – 70 år. 4. ECOG performance status ≤1. 5. Forventet levetid > 6 måneder. 6. Mindst et målbart parameter udover det kirurgisk fjernede væv i henhold til RECIST 1.1 kriterierne. 7. Ingen signifikant toksicitet eller bivirkninger (CTC ≤ 1) fra tidligere behandlinger, bortset fra sensorisk- eller motorisk neuropati (CTC ≤ 2) og/eller alopeci (CTC ≤ 2). 8. Acceptabel organfunktion. 9. Kvinder i den fertile alder skal bruge sikker prævention. Dette gælder fra inklusion indtil 6 måneder efter behandlingen. P-piller, spiral, depot injektion med gestagen, subdermale implantater, hormon vaginal ring og transdermalt depotplaster anses alle for sikker prævention. 10. Underskrevet samtykkeerklæring efter at have modtaget mundtlig og skriftlig information om studiet. 11. Være villig til at deltage i de planlagte kontroller og i stand til at håndtere toksiciteter. |
|
E.4 | Principal exclusion criteria |
1. A history of prior malignancies. Patients treated for another malignancy can participate if they are without signs of disease for a minimum of 5 years after treatment. 2. Known hypersensitivity to one of the active drugs or one or more of the excipients. 3. Severe medical conditions, such as severe asthma/COLD, significant cardiac disease, poorly regulated insulin dependent diabetes mellitus among others. 4. Creatinine clearence < 70 ml/min*. 5. Acutte/chronic infection with HIV, hepatitis, syphilis among others. 6. Severe allergies or previous anaphylactic reactions. 7. 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. 8. Pregnant women and women breastfeeding. 9. Simultaneous treatment with systemic immunosuppressive drugs (including prednisolone, methotrexate among others)**. 10. Simultaneous treatment with other experimental drugs. 11. Simultaneous treatment with other systemic anti-cancer treatments. 12. Patients with active and uncontrollable hypercalcaemia.
* In selected cases it can be decided to include a patient with a GFR < 70 ml/min with the use of a reduced dose of chemotherapy. ** In selected cases a systemic dose of ≤10 mg prednisolone or a transient planned treatment that can be stopped before TIL therapy can be tolerated. |
1. Tidligere kræftsygdom. Patienter behandlet for anden kræftsygdom kan deltage, hvis de er uden sygdomstegn minimum 5 år efter at have modtaget behandling for denne. 2. Kendt allergi mod et af de aktive stoffer eller et/flere af hjælpestofferne. 3. Alvorlig medicinsk komorbiditet som eksempelvis alvorlig astma/KOL, hjertesygdom, dårligt reguleret sukkersyge. 4. Kreatinin clearance < 70 ml/min*. 5. Akut/kronisk infektion med blandt andet HIV, hepatitis, syfilis. 6. Alvorlige allergier eller tidligere anafylaktisk reaktion. 7. Aktiv autoimmun sygdom som eksempelvis neutropeni/thrombocytopeni eller hæmolytisk anæmi, systemisk lupus erythematosis, Sjögren’s syndrom, sclerodermi, myasthenia gravis, Goodpasteur’s sygdom, Addison’s sygdom, Hashimotos thyroiditis, aktiv Graves sygdom. 8. Gravide- og ammende kvinder. 9. Samtidig behandling med systemisk immunsupprimerende medicin (inklusiv blandt andet prednisolon, metotrexat)**. 10. Samtidig behandling med anden eksperimentel medicin. 11. Samtidig behandling med anden anti-cancer medicin. 12. Patienter med aktiv og ukontrollabel hypercalciæmi.
* I udvalgte tilfælde tilfælde kan det besluttes at inkludere patienter med GFR < 70 ml/min ved brug af reduceret dosis kemoterapi. ** I udvalgte tilfælde kan en systemisk dosis ≤10 mg prednisolon eller en forbigående planlagt behandling tolereres. |
|
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 |