| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| metastatic renal cancer |
| carcinoma renale metastatico |
|
| E.1.1.1 | Medical condition in easily understood language |
| metastatic renal cancer |
| metastatic renal cancer |
|
| 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 | PT |
| E.1.2 | Classification code | 10050513 |
| E.1.2 | Term | Metastatic renal cell carcinoma |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| 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 |
| Overal Response Rate by irRC |
| Tasso di risposta globale, secondo irRC |
|
| E.2.2 | Secondary objectives of the trial |
| Toxicity, Overall Survival, Duration of response, PFS, ORR by RECIST 1.1, Prognostic and predictive marker response, Immunological response |
| Tossicità, Sopravvivenza Globale, durata della risposta, PFS, ORR secondo RECIST 1.1, markers prognostici e predittivi di risposta, risposta Immunologica |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Signed Written Informed Consent: patients must be willing and able to give written informed consent, that has to be given before starting of screening procedures.
2. Availability of autologous tumor tissue fulfilling acceptance criteria prescribed by the “Product Specification File”.
3. Patients must have histologically or cytologically confirmed RCC (all histology types except for urothelial cancer);
4. Patients must have stage IV disease in progression after at least 1 TKI and/or antiangiogenetic and/or mTOR inhibitors therapy
(patients must have finished prior treatments at least 4 weeks before the first IL2 dose)
5. Patients must have at least one measurable lesion, according to the irRC response criteria (see section 8 ), after asportation of tumor tissue for vaccine preparation. The tumor lesions that will be irradiated are excluded for response evaluation.
6. Life expectancy of greater than 3 months.
7. ECOG performance status 0-1
8. Patients must have organ and marrow function as defined below:
-leukocytes >4000/L
-absolute neutrophil count>1,500/L
-platelets >100,000/L
-total bilirubin within normal institutional limits (nil)
- AST(SGOT)/ALT(SGPT)<2.5 X institutional upper limit of normal
-creatinine< 1.5 mg/dl
- haemoglobin >8.0 gm/dl
- hematocrit <30%
9. ECG and echocardiography within normal institutional limits
10. Pulmonary function tests within normal institutional limits
11. No contraindication for the use of vasopressor agents
12. Negative screening tests for HIV, HBV HCV and syphilis not older than 30 days before performing any of the GMP-regulated activities required
13. Men and women aged > 18 years. |
1. Firma del consenso informato: I pazienti devono essere disposti e capaci a fornire il proprio consenso informato scritto prima di ogni altra procedura di screening prevista per lo studio.
2. Disponibilità di materiale tumorale raccolto e conservato secondo le procedure del Laboratorio di Terapia Cellulare Somatica IRST.
3. Diagnosi istologica o citologica confermata di RCC (tutte le istologie tranne carcinoma uroteliale)
4. Stadio IV, in progressione dopo almeno una linea di terapia con TKI e/o antiangiogenetici e/o inibitori di mTOR (i pazienti dovranno aver terminato i precedenti trattamenti almeno 4 settimane prima della prima dose di IL-2)
5. I pazienti dovranno avere almeno una lesione misurabile, secondo i criteri di risposta irRC (vedere sezione 8), dopo asportazione del tessuto tumorale per la preparazione dei vaccini. Le lesioni tumorali che verranno irradiate sono esclusi dalla valutazione della risposta.
6. Aspettativa di vita superiore a 3 mesi
7. ECOG performance status 0-1
8. Funzionalità midollare e d’organo definite come:
-leucociti>4000/L
-neutrofili >1,500/L
-piastrine>100,000/L
-bilirubina totale nei limiti della norma (nil)
- AST(SGOT)/ALT(SGPT) <2.5 X institutional upper limit of normal
- creatinina< 1.5 mg/dl
- emoglobina >8.0 gm/dl
- ematocrito <30%
9. ECG ed ecocardiogramma nella norma
10. Normale funzionalità polmonare
11. Non controindicazioni nell’uso di agenti vasopressori
12. Test per HIV, HBV HCV e sifilide negativi non più vecchi di 30 giorni prima dell’esecuzione di qualunque procedura GCP.
13. Uomini e donne di età superiore a 18 anni. |
|
| E.4 | Principal exclusion criteria |
1.Patients who have positive tests to HCV, HBV, HIV, or syphilis (specific blood testing must be performed within 30 days before
any GMP-regulated activity).
2.Patients who did not have prior lines of systemic therapy for advanced disease.
3.Participation in another clinical trial with any investigational agents within 30 days prior to study screening.
4.Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure,
unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study
requirements (on physician’s judgment).
5.Other known malignant neoplastic diseases in the patient’s medical history with a disease-free interval of less than 3 years
(except for previously treated basal cell carcinoma and in situ carcinoma of the uterine cervix);
6.Patients who have had chemotherapy or radiotherapy or immunotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin
C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4
weeks earlier.
7.Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because
they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
8.History of allergic reactions attributed to compounds of similar chemical or biologic composition to IL-2 or other agents used in
the study.
9.Any autoimmune disease which could be exacerbated by IL-2
10.A medical illness requiring chronic treatments with corticosteroids or other immunosuppressive agents
11.A history of significant cardiovascular disease, including myocardial infarction, congestive heart failure, primary cardiac
arrhythmias, angina pectoris or cerebrovascular accident
12.HIV-positivity, whether or not symptomatic
13.Any contraindication to undergo leukapheresis as evaluated by transfusionist (e.g. severe anemia, piastrinopenia, oral
anticoagulant therapy) or to undergo surgery. |
1. I pazienti che hanno test positivi per HCV, HBV, HIV, o sifilide (test ematici specifici devono essere effettuati entro 30 giorni
prima di qualsiasi attività regolamentata dalle GMP).
2. I pazienti che non hanno avuto precedenti linee di terapia sistemica per malattia avanzata.
3. Partecipazione ad un altro studio clinico con eventuali farmaci sperimentali nei 30 giorni precedenti allo screening per questo studio.
4. malattia non controllata intercorrente tra cui, ma non solo, l'infezione in corso o attiva, insufficienza cardiaca congestizia sintomatica, angina pectoris instabile, aritmia cardiaca, o malattia psichiatrica / situazioni sociali che limiterebbero la conformità
con i requisiti di studio (a giudizio del medico).
5. Altre note patologie neoplastiche maligne nella storia clinica del paziente, con un intervallo libero da malattia di meno di 3 anni (tranne che per il carcinoma a cellule basali e carcinoma in situ della cervice uterina trattati precedentemente);
6. Precedente chemioterapia, radioterapia o immunoterapia entro 4 settimane (6 settimane per nitrosouree o mitomicina C) prima di entrare nello studio o pazienti che non hanno recuperato da eventi avversi a causa di agenti somministrati più di 4 settimane prima.
7. I pazienti con note metastasi cerebrali dovrebbero essere esclusi da questo studio clinico a causa della loro scarsa prognosi e
perché spesso sviluppano una progressiva disfunzione neurologica che confonderebbe la valutazione degli eventi avversi di tipo
neurologico e non.
8. Storia di reazioni allergiche attribuite a composti chimici o biologici simili all'IL-2 o ad altri agenti utilizzati nello studio.
9. Ogni malattia autoimmune che potrebbe essere aggravata da IL-2
10. Una condizione medica che richiede trattamenti cronici con corticosteroidi o altri farmaci immunosoppressori
11. Una storia di malattia cardiovascolare significativa, tra cui infarto miocardico, insufficienza cardiaca congestizia, aritmie
cardiache primarie, angina pectoris o incidente cerebrovascolare
12. HIV-positività, anche sintomatica
13. Qualsiasi controindicazione a sottoporsi a leucaferesi, come valutato dal transfusionista (ad esempio una grave anemia, piastrinopenia, terapia anticoagulante orale) o a sottoporsi ad un intervento chirurgico. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Overal Response Rate by IrRC |
| Tasso di Risposta Globale, secondo irRC |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
| Prognostic and predictive marker response |
| markers prognostici e predittivi di risposta |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| 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 | Yes |
| E.6.13.1 | Other scope of the trial description |
| Immunological response |
| Risposta immunitaria |
|
| 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 | Information not present in EudraCT |
| E.8.1.6 | Cross over | Information not present in EudraCT |
| 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.8.2.4 | Number of treatment arms in the trial | 1 |
| 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.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.5.1 | Number of sites anticipated in the EEA | 1 |
| 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 | Information not present in EudraCT |
| E.8.7 | Trial has a data monitoring committee | Yes |
| 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
|
|
| 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 | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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