E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with operable rectal cancer |
Pazienti affetti da carcinoma del retto operabile |
|
E.1.1.1 | Medical condition in easily understood language |
patients with rectal cancer |
pazienti affetti da tumore del retto |
|
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 | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10062099 |
E.1.2 | Term | Rectal neoplasm |
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 |
we propose a randomized non-inferiority trial that compares preoperative FUbased
chemoradiotherapy to radiotherapy with a simultaneous integrated boost. In case of
non-inferiority, the latter approach is considered preferential with regard to toxicity and cost.
The metabolic response of the tumor, as assessed by 18F-FDG PET or PET-CT, will be used
as a surrogate marker of cause specific outcome. |
Confrontare l’efficacia, in termini di Risposta Metabolica (PET-CT), della sola Radioterapia con Simulataneous Boost (IMRT-IGRT) versus la Chemioradioterapia Standard nei pazienti con carcinoma del retto operabile, stadio T3-T4, N0-2, M0 (o metastasi resecabile). |
|
E.2.2 | Secondary objectives of the trial |
Secondary endpoints:
histological downgrading, according to the Dworak classification (13)
number of R0, R1 and R2 resections
acute and late toxicity, according the NCI Common Terminology Criteria for Adverse
Events v3.0 (CTCAE)
local control
progression free survival
survival
quality of life
cost evaluation |
Confrontare i due trattamenti in termini di:
- Grado di Regressione Tumorale (Dworak score)
- Tasso di resezione R0, R1,R2
- Tossicità acuta e tardiva (NCI-CTCAEs, versione 3.0)
- Controllo locale di malattia
- Sopravvivenza libera da malattia
- Sopravvivenza globale |
|
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 |
LIFE QUALITY: Vers:CRO_28-12- Date:2010/12/28 Title:Prospective evaluation of Quality of Life in patients with rectal cancer treated with preoperative radiation therapy alone with simultaneous boost or chemoradiotherapy (IMRT-IGRT_SIB)(CRO-2010-14). Objectives:Evaluation and comparison of changes of impact on quality of life deriving from the two different treatment arms of the study (EORTC QLC-C30 e QLC-CR29)
OTHER SUBSTUDIES: Evaluation of molecular predictive and prognostic factors on tissue and peripheral blood samples. October 2011, version 1
|
QUALITA DELLA VITA: Vers:CRO_28-12- Data:2010/12/28 Titolo:Valutazione prospettica della qualità di vita nei pazienti affetti da neoplasia del retto sottoposti a radioterapia con simultaneous boost (IMRT-IGRT_SIB) o chemio radioterapia preoperatoria e chirurgia nell’ambito dello studio Rectum SIB di fase III (CRO-2010-14). Obiettivi:Lo studio ha lo scopo di valutare e mettere a confronto i cambiamenti di qualità di vita nei pazienti con carcinoma del retto trattati con sola radioterapia o con chmioradioterapia(EORTC QLC-C30 e QLC-CR29)
ALTRI SOTTOSTUDI: Determinazione di fattori molecolari prognostici e predittivi su campioni di tessuto e di sangue. Data: Ottobre 2011, versione 1
|
|
E.3 | Principal inclusion criteria |
Eligibility criteria include histopathologically confirmed rectal adenocarcinoma with an
inferior border within 15 cm of the anal verge. The tumor has to have evidence of T3 or T4
disease on MRI or endoluminal ultrasound. Patients with unresectable mestastatic disease,
with an ECOG performance status > 3 and patients not deemed fit for radiotherapy,
capecitabine or surgery are excluded. Pregnant or lactating patients, women with child
bearing potential who lack effective contraception and patients below 18 years old are
excluded as well |
Criteri di inclusione
- Pazienti con adenocarcinoma del retto, confermato dall’esame istologico
- Polo inferiore della neoplasia ≤15 cm dal margine anale (rettoscopia)
- Stadio T3 o T4 definito con RM o EUS
- Esami ematochimici entro 14 giorni dall’arruolamento: Ematologia: neutrofili ≥1.5 x 109/L, piastrine >100 x109/L. Biochimica: transaminasi ≤2.5 ULN e fosfatasi alcalina ≤2.5 ULN, creatinina clearance calcolata ≥ 60 mL/min. Laboratory
- Qualsiasi condizione non controllata che precluda la possibilità di eseguire un trattamento radioterapico o chemioterapico o un intervento chirurgico
- Malattia cardiaca non clinicamente rilevante
- Firma del consenso informato in accordo con ICH/GCP. |
|
E.4 | Principal exclusion criteria |
- ECOG Performance status >3
- previous pelvic radiation therapy and/or chemotherapy
- patients with inoperable rectal cancer
- unresectable distant metastases |
- ECOG Performance status >3
- Precedente radioterapia sull’addome o chemioterapia, o non suscettibile di intervento chirurgico.
- Presenza di metastasi a distanza non resecabili
- Pazienti in gravidanza o in allattamento
- Pazienti in periodo riproduttivo senza adeguate misure contraccettive.
- Pazienti con età < 18 anni |
|
E.5 End points |
E.5.1 | Primary end point(s) |
we propose a randomized non-inferiority trial that compares preoperative FUbased
chemoradiotherapy to radiotherapy with a simultaneous integrated boost. In case of
non-inferiority, the latter approach is considered preferential with regard to toxicity and cost.
The metabolic response of the tumor, as assessed by 18F-FDG PET or PET-CT, will be used
as a surrogate marker of cause specific outcome. |
Confrontare l’efficacia, in termini di Risposta Metabolica (PET-CT), della sola Radioterapia con Simulataneous Boost (IMRT-IGRT) versus la Chemioradioterapia Standard nei pazienti con carcinoma del retto operabile, stadio T3-T4, N0-2, M0 (o metastasi resecabile). |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
4-6 weeks after preoperative treatment |
4-6 settimane dopo il trattamento preoperatorio |
|
E.5.2 | Secondary end point(s) |
Histological tumor regression grade |
grado di regressione tumorale all'esame istologico |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
6-8 weeks after preoperative treatment |
6-8 settimane dopo il trattamento preoperatorio |
|
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 | No |
E.6.5 | Efficacy | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
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 |
chemioradioterapia vs radioterapia da sola |
chemoradiotherapy vs RT alone |
|
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 8 |
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |