| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Stage III and high-risk stage II colon cancer |
| Tumori del colon di stadio III e II alto rischio |
|
| E.1.1.1 | Medical condition in easily understood language |
| Colon cancer |
| Tumori del colon |
|
| 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 | PT |
| E.1.2 | Classification code | 10061451 |
| E.1.2 | Term | Colorectal cancer |
| 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 |
The primary objective is to study the feasibility of using liquid biopsy to guide the post-surgical and post-adjuvant clinical management of stage III and high-risk stage II (T4N0) MSS colon cancer patients.
Feasibility is defined as the ability of at least two subsequent negative ctDNA determination to identify patients that will be NED (without radiologic evidence of metastasis) 2 years aftersurgery |
L’obiettivo primario dello studio è di studiare la fattibilità di usare la biopsia liquida per guidare la gestione clinica post-chirurgica e post-adiuvante dei pazienti affetti da tumori MSS del colon di stadio III e II ad alto rischio (T4N0).
La fattibilità è definita come la capacità di almeno 2 biopsie liquide consecutive negative di identificare i pazienti che a 2 anni dalla chirurgia non hanno evidenza radiologica di remissione metastatica. |
|
| E.2.2 | Secondary objectives of the trial |
- To compare the DFS and OS rates at 2,3 and 5 years in a cohort of 140 stage III and high-risk stage II (only T4N0) MSS colon cancer patients treated post-surgically with a LB guided strategy, with the DFS and OS rates of a 1:3 phenotypically matched cohort of the TOSCA trial treated with FOLFOX/CAPOX either at 3 or 6 months.
• To compare the safety profile in a cohort of 140 stage III and high-risk stage II (only T4N0) MSS colon cancer patients treated with a liquid biopsy-guided strategy, with the safety profile of 1:3 phenotypically matched cohort of the TOSCA trial treated with FOLFOX/CAPOX at 3 or 6 months.
• To validate LB seroconversion as a proxy of therapy efficacy and to compare its performance with CEA testing
whenever CEA levels are above the normal values.
• To study the QoL of patients in a cohort of 140 stage III and high-risk stage II (only T4N0) MSS colon cancer patients treated post-surgically with a liquid biopsy-guided strategy |
Confrontare le % DFS e OS a 2,3,5 anni in una coorte di 140 pazienti con cancro MSS del colon stadio III e II ad alto rischio trattati postchirurgicamente con strategia terapeutica guidata da LB, con le % di DFS e OS di una coorte storica accoppiata in rapporto 1:3 dallo studio clinico TOSCA trattati con FOLFOX/CAPOX per 3 o 6 mesi.
Confrontare il profilo di sicurezza in una coorte di 140 pazienti con cancro MSS del colon di stadio III e II ad alto rischio trattati postchirurgicamente con strategia terapeutica guidata da LB, con quello di una coorte storica accoppiata in rapporto 1:3 dallo studio clinico TOSCA trattati con FOLFOX/CAPOX per 3 o 6 mesi.
Validare la sieroconversione della LB come surrogato dell’efficacia della terapia e confrontarla con la misurazione del CEA quando è sopra i livelli normali.
Studiare la QoL in una coorte di 140 pazienti con cancro del colon MSS di stadio III e II ad alto rischio trattati postchirurgicamente con una strategia terapeutica guidata da LB. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Pegasus trial written informed consent.
2. Age = 18 years.
3. Histologically confirmed diagnosis of operable stage III or T4N0 stage II colon cancer located 12 cm from the anal verge by endoscopy and above the peritoneal reflection at surgery.
4. Availability of plasma collected prior to surgery.
5. Availability of the original FFPE tumor tissue.
6. Acceptance to undergo at least all the interventional liquid biopsies.
7. ECOG performance status 0-1.
8. Normal organ functions. (as defined in section 9.3)
9. Women with childbearing potential should complete a pregnancy test and be willing to use highly effective contraceptive methods. |
1. Consenso informato scritto dello studio Pegasus.
2. Età = 18 anni.
3. Diagnosi istologica di tumore operabile del colon di stadio III e II (T4N0), localizzato a 12 cm dal margine anale all’endoscopia e sopra la
piega peritoneale alla chirurgia.
4. Disponibilità di un prelievo di plasma pre-chirurgico.
5. Disponibilità del blocchetto di tessuto tumorale FFPE.
6. Accettazione di eseguire almeno tutte le biopsie liquide interventistiche.
7. Stato della condizione secondo ECOG 0-1.
8. Funzioni d’organo normali (come definito nella sezione 9.3).
9. Donne in età fertile dovranno eseguire un test di gravidanza e dovranno accettare di utilizzare metodi contracettivi altamente efficaci |
|
| E.4 | Principal exclusion criteria |
1. Patients having a MSI-H/MMRd tumor are excluded from the study (done according to standard clinical practice).
2. History of another neoplastic disease, unless in remission for = 5 years. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
3. Had an incomplete diagnostic colonoscopy and/or polyps removal.
4. Macroscopic or microscopic evidence of residual tumor (R1 or R2 resections). Patients should never have had any evidence of metastatic disease (including presence of tumor cells in the peritoneal lavage).
5. Current or recent treatment with another investigational drug or participation in another investigational study
6. Patient unable to comply with the study protocol owing to psychological, social or geographical reasons.
7. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study.
8. Inadequate contraception (male or female patients) if of childbearing or procreational potential.
9. Clinically relevant cardiovascular disease.
10. Acute or subacute intestinal occlusion or history of inflammatory bowel disease.
11. Pre-existing neuropathy > grade 1. Known grade 3 or 4 allergic reaction to any of the components of the treatment.
12. Has a known Gilbert Syndrome or UGT1A1 homozygous *28/*28 germline variant.
13. Has a known history of Human Immunodeficiency Virus (HIV). Note: No HIV testing is required.
14. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive)or known active Hepatitis C virus infection. Note: no testing for Hepatitis B and Hepatitis C isrequired unless mandated by local health authority.
15. Has a known history of active TB (Bacillus Tuberculosis). |
1. I pazienti con tumori MSI-H/MMRd sono esclusi dallo studio (il test viene eseguito secondo pratica clinica)
2. Storia di un’altra malattia neoplastica, a meno che in remissione da = 5 anni. I Pazienti con carcinoma basale della pelle, carcinoma squamoso della pelle, o carcinoma in situ (as es. al seno o alla cervice) che sono andati incontro a terapia con intento curativo non sono esclusi.
3. Hanno effettuato una colonscopia diagnostica non completa e/o con rimozione incompleta dei polipi.
4. Evidenza macroscopica o microscopica di tumore residuo (reseazione R1 o R2). I pazienti non devono mai avere avuto nessuna evidenza di malattia metastatica (inclusa la presenza di cellule tumorali nel lavaggio
peritoneale).
5. Trattamento in corso o recente con un altro farmaco sperimentale o partecipazione in un altro studio clinico.
6. Pazienti incapace di attenersi al protocollo di studio a causa di ragioni psicologiche, sociali o geografiche.
7. È una donna gravida o in allattamento, o in programma di concepire (sia uomo che donna) durante la durata dello studio.
8. Pazienti (uomo e donna) che eseguono contraccezione inadeguata se fertili.
9. Malattie cardiovascolari clinicamente rilevanti.
10. Occlusione intestinale acuta o subacute, o storia di malattia cronica infiamamtoria intestinale.
11. Neuropatia pre-esistente di grado >1. Allergia di grado 3 o 4 a qualsiasi componente dei trattamenti.
12. Ha la sindrome di Gilbert o variante germinale UGT1A1 *28/*28 in omozigosi.
13. Storia nota di infezione da HIV. Nota: il test per HIV non è richiesto.
14. Storia nota di infezione da Epatite B (definita come reattività all’antigene di superfice [HBsAg]) o infezione nota in corso da EpatiteC. Nota: nessun test per Epatite B e C è necessario a meno che richiesto dalle autorità sanitarie locali
15. Storia nota di infezione attiva di Tubercolosi (Bacillus Tuberculosis). |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Number of post-surgery and post-adjuvant false negative cases after a double ctDNA-negative detection, defined as cases that become positive at subsequent interventional LB or that experience radiological relapse within 2 years. |
Numero di casi falsi negativi post-chirugici e post-adiuvanti dopo una doppia biopsia liquida negativa, definiti come casi che diventano positivi ad una successiva biopsia liquida o che vanno incontro a remissione radiologica entro
i 2 anni dalla chirurgia. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| within 2 years from surgery |
| 2 anni dalla chirurgia |
|
| E.5.2 | Secondary end point(s) |
| Safety and tolerability avvording to CTCAE version 4.03; Disease-Free Survival (DFS) at 2 and 3-years, Overall Survival (OS) at 5-years.; Number of patients experiencing ctDNA seroconversion (i.e. ctDNA+ that become ctDNA-) after any chemotherapy regimen remaining disease free at 2 and 3 years.; Assessment of QLQ-C30 and CR-29 EORTC questionnaires |
| Sicurezza e tollerabilità secondo la versione 4.03 del CTCAE; Sopravvivenza libera da malattia (DFS) a 2 e 3 anni, Sopravvivenza (OS) a 5 anni; Numero di pazienti in cui si ha sieroconversione (ovvero LB positiva che diventa negativa) dopo qualsiasi chemioterapia e che rimangono liberi da malattia a 2 e 3 anni.; Compilazione ed analisi dei questionari EORTC QLQ-C30 e CR-29 |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| the whole study; 2, 3 and 5 years; at 2 and 3 years; the whole study |
| durante tutto lo studio; 2, 3 e 5 anni; 2 e 3 anni; durante tutto lo studio |
|
| 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 |
| Feasibility of using liquid biopsy to guide post-surgical and post-adjuvant clinical management of patients with colon cancer |
| Feasibility of using liquid biopsy to guide post-surgical and post-adjuvant clinical management of patients with colon cancer |
|
| 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 | Yes |
| 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 | Yes |
| E.8.2.3.1 | Comparator description |
| coorte storica di studio clinico TOSCA |
| historical cohort of the TOSCA clinical trial |
|
| 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
| 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 | 6 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 9 |
| 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
|
|
| 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 | 4 |
| 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 | 4 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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