E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
COLORECTAL METASTATIC CANCER |
CARCINOMA COLON-RETTO METASTATICO |
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E.1.1.1 | Medical condition in easily understood language |
COLORECTAL METASTATIC CANCER |
CARCINOMA COLON-RETTO METASTATICO |
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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 | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10052362 |
E.1.2 | Term | Metastatic colorectal cancer |
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 |
Objective response rate |
Tasso di risposte obiettive. |
|
E.2.2 | Secondary objectives of the trial |
Toxicity
Quality of Life (QoL)
Progression Free Survival (PFS)
Overall Survival (OS) |
Tossicità.
Valutazione della qualità di vita.
Sopravvivenza libera da progressione (PFS).
Sopravvivenza globale (OS). |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Other types of substudies Specify title, date and version of each substudy with relative objectives: TRANSLATE - TRANSLATIONAL
version 1.0, 08feb2016
Objectives
Analysis of changes of major circulating immunologic factors during the TRANSLATE study.
Analysis impact of the observed changes (if any) on the patients’ outcome.
Analysis of immunologic status at progression.
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Altre tipologie di sottostudi specificare il titolo, la data e la versione di ogni sottostudio con i relativi obiettivi: TRANSLATE - TRANSLATIONAL
versione 1.0, 08/02/2016
Obiettivi
Analizzare le variazioni fra i maggiori fattori immunologici circolanti durante lo studio TRANSLATE.
Analizzare l’impatto dei cambiamenti osservati (se presenti) sull’outcome del paziente.
Analizzare lo stato immunitario alla progressione di malattia.
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E.3 | Principal inclusion criteria |
Hystologically confirmed CRC
Metastatic disease previously treated with at least two lines of sistemic therapy.
Measurable disease (RECIST criteria).
At least one metastatic site suitable for irradiation.
Signed informed consent.
Geographical accessibility.
Age ¿ 18 y.o.
Karnofsky P.S. >=60%
Life expectancy > 3 months.
Adequate bone marrow function (Absolut Neutrophil count >=1,5 x 109/l, platelets>=¿100 x 109/l, hemoglobin >=¿10 g/dL).
Adequate liver function: transaminases = 2.5 x upper limit of normality (ULN); bilirubin = 1.5 x ULN.
Adequate renal function: Creatinine = ULN or creatinine clearance > 60 mL/min (Cockroft-Gault).
Adequate contraception for childbearing potential women.
Adequate cardiac function.
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• Diagnosi istologica di adenocarcinoma del colon-retto
• Malattia metastatica pretrattata con almeno due linee di trattamento comprendenti antiVEGF se non controindicati e anti EGFR se RAS wild type.
• Malattia misurabile secondo i criteri RECIST .
• Almeno una sede di malattia metastatica suscettibile di trattamento radioterapico.
• Consenso informato scritto.
• Accessibilità geografica.
• Età superiore ai 18 anni.
• Karnofsky Performance Status >= 60% (allegato 1).
• Aspettativa di vita > 3 mesi.
• Adeguato profilo ematologico: conta assoluta dei neutrofili (ANC) =1,5 x 109/l, piastrine =100 x 109/l, emoglobina =10 g/dL.
• Adeguata funzionalità epatica: transaminasi = 2,5 volte il limite superiore di normalità (ULN), bilirubina totale = 1,5 volte l’ULN.
• Adeguata funzionalità renale: creatinina sierica = ULN o clearance della creatinina calcolata (Cockroft-Gault) > 60 mL/min.
• Le donne in età fertile devono usare un metodo contraccettivo adeguato. Gli uomini fertili, se le loro partner sono in età fertile, devono usare un metodo contraccettivo adeguato durante tutto lo studio.
• Adeguata funzionalità cardiaca.
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E.4 | Principal exclusion criteria |
Prior malignancies
Prior organ transplantation
Brain metastasis
Autoimmune or allergic disorders
Previous HBV or HCV infections
Previous IL2 treatment
Active steroid therapy
Any active infection requiring specific treatment (Antibiotics, antimicotic, antiviral)
Radiotherapy within 6 weeks before enrollment.
Pregnant or lactating females.
Other non-malignant uncontrolled systemic diseases or social conditions that would preclude trial entry in the opinion of the investigator.
IL-2 treatment contraindications:
1. Hypersensitivity to the active ingredient or to any excipient.
2. Inadequate bone marrow function: WBC <2900 mm3 and/or HCT <30% and/or platelets count <90000 mm3.
3. Uncontrolled serous effusions (pleural, pericardic or peritoneal)
4. Blood Pressure <60 mmHg.
5. Pregnancy or breast feeding.
6. Active infections.
7. Brain metastases.
Cyclophosphamide treatment contraindications:
1. Cystitis.
2. Urinary Obstruction.
3. Inadequate bone marrow function: WBC <2900 mm3 and/or HCT <30% and/or platelets count <90000 mm3.
4. Active infections.
5. Pregnancy or breast feeding.
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• Pregresse neoplasie maligne d'altra origine nei precedenti 5 anni (esclusi tumori della cute, non melanoma) .
• Trapianti d'organo.
• Metastasi cerebrali.
• Patologia autoimmune o patologia allergica.
• Pregresse infezioni da HBV e/o HCV.
• Pregresso trattamento con IL2.
• Trattamento attivo con cortisonici.
• Malattia infettiva in atto che necessita di terapia specifica (antibiotica, antivirale o antimicotica).
• Radioterapia nelle 6 settimane precedenti l’arruolamento.
• Controindicazioni al trattamento con Interleukina-2:
1. Ipersensibilità ai principi attivi o a uno qualsiasi degli eccipienti.
2. Funzione midollare gravemente compromessa: globuli bianchi totali <2900 mmc e/o Ematocrito <30% e/o Piastrine <90000 mmc.
3. Ipersensibilità ai principi attivi o a uno qualsiasi degli eccipienti.
4. Versamenti sierosi non controllati (pleurici, pericardici, peritoneali).
5. Pressione arteriosa < 60 mmHg a riposo.
6. Gravidanza o allattamento.
7. Infezioni in atto.
8. Metastasi cerebrali note.
• Controindicazioni al trattamento con Ciclofosfamide:
1. Cistite.
2. Ostruzione flusso urinario.
3. Funzione midollare gravemente compromessa: globuli bianchi totali <2900 mmc e/o Ematocrito <30% e/o Piastrine <90000 mmc.
4. Infezioni in atto.
5. Gravidanza o allattamento.
• Presenza di altra condizione non oncologica non controllata o condizioni sociali che precludano l’entrata in studio nell’opinione del clinico.
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E.5 End points |
E.5.1 | Primary end point(s) |
Objective response rate |
Tasso di risposte obiettive. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
during treatment |
durante il trattamento |
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E.5.2 | Secondary end point(s) |
Toxicity; QoL; Progression Free Survival; Overall Survival |
Tossicità; Valutazione della qualità di vita; Sopravvivenza libera da progressione; Sopravvivenza globale |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
during treatment and during 4 weeks after the end of treatment; every cycle and at the end treatment; from study entry to first documented disease progression or death from any cause ; from study entry to death from any cause |
durante il trattamento e nelle 4 settimane successive al termine del trattamento; ad ogni ciclo e a fine trattamento; dall'entrata in studio al primo riscontro di progressione di malattia o morte per qualsivoglia causa; dall'entrata in studio alla morte per qualunque causa |
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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 | No |
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
| 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 | 5 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 5 |
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 | 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
|
Death of all enrolled patients |
decesso di tutti i pazienti arruolati |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 36 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 36 |
E.8.9.2 | In all countries concerned by the trial days | 0 |