| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Patients with Previously Untreated Metastatic Colorectal Cancer |
| Pazienti affetti da neoplasia del Colonretto Metastatico Precedentemente Non Trattato |
|
| 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 | 10052358 |
| E.1.2 | Term | Colorectal cancer metastatic |
| 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 of the study is to determine:
• The efficacy of AZD2171 in combination with 5-fluorouracil (5 FU), leucovorin, and oxaliplatin (FOLFOX) compared to the efficacy of bevacizumab in combination with FOLFOX by assessment of progression free survival (PFS). |
L'obiettivo primario dello studio e' determinare:
• L'efficacia di AZD2171 in combinazione con 5-fluorouracile (5 FU), leucovorina, e oxaliplatino (FOLFOX) a confronto con l'efficacia di bevacizumab in combinazione con FOLFOX tramite la valutazione di sopravvivenza in assenza di progressione (PFS). |
|
| E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are to determine:
1. The efficacy of AZD2171 in combination with FOLFOX compared to the efficacy of bevacizumab in combination with FOLFOX by assessment of overall survival (OS), overall response rate (ORR; complete response [CR] + partial response [PR]) and duration of response.
2. The safety and tolerability of randomised study therapies in combination with FOLFOX.
3. The effects on quality of life (QoL) and disease-related symptoms of AZD2171 in combination with FOLFOX, compared with the effects of bevacizumab in combination with FOLFOX. |
Gli obiettivi secondari dello studio consistono nel determinare:
1.L'efficacia di AZD2171 in combinazione con FOLFOX a confronto con l'efficacia di bevacizumab in combinazione con FOLFOX tramite valutazione della sopravvivenza totale (overall survival o OS),velocita' di risposta totale (overall response rate o ORR; risposta completa [complete response o CR] + risposta parziale [partial response o PR]) e durata della risposta.
2.La sicurezza e la tollerabilita' delle terapie in studio randomizzate in combinazione con FOLFOX.
3.Gli effetti di AZD2171 in combinazione con FOLFOX,a confronto con gli effetti di bevacizumab in combinazione con FOLFOX sulla qualita' della vita (QoL) e sui sintomi correlati alla patologia |
|
| 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 |
PHARMACOGENETIC:
Vers:
Date:
Title:
Objectives:
PHARMACOKINETIC/PHARMACODYNAMIC:
Vers:
Date:
Title:
Objectives:
LIFE QUALITY:
Vers:
Date:
Title:
Objectives:
|
FARMACOGENETICA:
Vers:
Data:
Titolo:archival tumour samples
Obiettivi:
FARMACOCINETICA/FARMACODINAMICA:
Vers:
Data:
Titolo:blood samples for biomarkers/RECIST response
Obiettivi:
QUALITA DELLA VITA:
Vers:
Data:
Titolo:EuroQol-5 Dimension Health status Measure (EQ-5D)
Obiettivi:
|
|
| E.3 | Principal inclusion criteria |
| 1. Provision of written informed consent. 2. Males or females aged 18 years and older. 3. Histological or cytological confirmation of carcinoma of the colon or rectum. 4. Stage IV (metastatic) disease with one or more measurable lesions at least 10 mm in the longest diameter by spiral computed tomography scan or 20 mm with conventional techniques (RECIST criteria). 5. Patients must have received no prior systemic therapy for metastatic disease, except adjuvant therapy >12 months prior to study entry. 6. World Health Organisation (WHO) Performance score inferior to 2. 7. Life expectancy of major or equal to 12 weeks. Genetic research For inclusion in the genetic research component of the study, patients must fulfil the following criterion: 1. Provision of informed consent for genetic research. If a patient declines to participate in the genetic research, there will be no penalty or loss of benefit to the patient. The patient will not be excluded from other aspects of the study described in this Clinical Study Protocol, so long as they consent. |
| 1. Consenso informato firmato 2. Maschi o femmine di eta' uguale o superiore ai 18 anni 3. Conferma citologica o istologica di adenocarcinoma del colon o del retto 4. Stadio IV di malattia (metastatica) con una o piu' lesioni misurabili del diametro maggiore di almeno 10 mm se valutate con la CT-scan spirale oppure di almeno 20 mm di diametro se valutate con le altre tecniche convenzionali (RECIST) 5. I pazienti devono aver ricevuto un precedente trattamento per malattia metastatica, ad eccezione della terapia adiuvante > 12 mesi prima dell'ingresso in studio 6. World Health organization (WHO) Performance inferiore a 2 7. Aspettativa di vita maggiore o uguale a 12 mesi Ricerca Genetica Per l'inclusione nella parte dello studio dedicata alla ricerca genetica, i patienti dovranno soddisfare il seguente criterio: 1. Aver fornito un ulteriore consenso informato specifico per la ricerca genetica. La decisione di non aderire allo studio genetico non penalizzera' e neppure avra' conseguenze sul beneficio del paziente. Il paziente non sara' escluso dalle altre procedure dello studio fino a che non ne fara' espressamente richiesta. |
|
| E.4 | Principal exclusion criteria |
Any of the following is regarded as a criterion for exclusion from the study:
1. Adjuvant therapy within 12 months of study entry.
2. Any unresolved toxicity >CTC grade 2 from previous treatments.
3. Prior therapy with monoclonal antibodies or small molecule inhibitors against VEGF or VEGF receptors, including bevacizumab and AZD2171.
4. Prior therapy with oxaliplatin within 12 months of study entry.
5. Untreated brain or meningeal metastases. Patients with treated and radiological or clinical evidence of stable brain metastases are eligible if asymptomatic and corticosteroids are not required (patients must have discontinued steroids at least 4 weeks prior to registration).
6. Inadequate bone marrow reserve as demonstrated by an absolute neutrophil count ≤1.5 x 109/L or platelet count ≤100 x 109/L or requiring regular blood transfusions to maintain haemoglobin >9 g/dL.
7. Serum bilirubin ≥1.5 x upper limit of reference range (ULRR).
8. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥2.5 x ULRR. If liver metastases are present, ALT or AST ≥5 x ULRR.
9. Serum creatinine ≥1.5 x ULRR or a creatinine clearance of ≤50 mL/min calculated by Cockroft-Gault formula (see Section 4.7.2.2).
10. Greater than +1 proteinuria on 2 consecutive dipsticks taken no less than 1 week apart unless urinary protein, <1.5 g in a 24 hour urine collection.
11. Patients with a history of poorly controlled hypertension with resting BP >150/100 mmHg in the presence or absence of a stable regimen of anti hypertensive therapy. Measurements will be made after the patient has been resting supine for a minimum of 5 minutes. Two or more readings should be taken at 2 minute intervals and averaged. If the first 2 diastolic readings differ by more than 5mmHg, then an additional reading should be obtained, and averaged.
Please see Protocol for other criteria |
1. Precedente terapia adiuvante nei 12 mesi precedenti l'ingresso nello studio
2. Una tossicita' di grado maggiore di 2 (secondo i parametri internazionali CTC) non risolta dai precedenti trattamenti
3. Precedente terapia con anticorpi monoclonali o piccole molecole inibitrici di VEGF o di recettori VEGF, inclusi bevacizumab e AZD2171
4. Precedente terapia con oxaliplatino nei 12 mesi precedenti l'ingresso nello studio
5. Metastasi cerebrali o meningee non trattate in precedenza. Pazienti con un'evidenza strumentale o clinica di metastasi cerebrali stabili trattate sono elegibili se sono asintomatici e non richiedono una terapia con corticosteroidi (i pazienti devono aver interrotto la terapia con farmaci steroidei almeno 4 settimane prima della registrazione nello studio.
6. Inadeguata riserva midollare: neutrofili assoluti ≤ 1.5 x 109/L oppure piastrine ≤100 x 109/L. Oppure pazienti che richiedono regolari trasfusioni di sangue per mantenere l'emoglobina ≥ 9 g/dL
7. Bilirubina sierica ≥ 1.5 il limite piu' alto del range di riferimento (ULRR)
8. ALT o AST ≥ 2.5 x ULRR. In presenza di metastasi epatiche ≥ 5 x ULRR
9. Creatinina sierica ≥ 1.5 x ULRR oppure clearance del valore di ≤ 50 mL/min calcolata secondo la formula di Cockroft-Gault
10. Proteinuria maggiore di +1 mediante 2 consecuitivi valutazioni con sticks fatte a distanza di almeno una settimana oppure proteine nell'urina ≥ 1.5 g mediante valutazione fatta nelle 24 ore
11. Pazienti con una storia di ipertensione non controllata con valori della pressione diastolica a riposo maggiori di 150/110 mmHg in presenza o assenza di uno stabile regime terapeutico antiipertensivo. Le valutazioni devono essere fatte dopo che il paziente e' stato fatto riposare supino per un minimo di 5 minuti. Due o piu' letture dovrebbero essere eseguite ad intervalli di 2 minuti e valutarne la media. Se le prime due letture differiscono di piu' di 5 mmHg, dovra' essere eseguita un'ulteriore valutazione.
Si veda protocollo per altri criteri |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Primary outcome variable is:
PFS |
| La variabile di endpoint primario dello studio e' la sopravvivenza libera da progressione |
|
| 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 | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | Yes |
| 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 | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| 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) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 3 |
| 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 | 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 | 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
|
| Ultima visita dell`ultimo paziente per ogni attivita` relativa al protocollo; i pazienti che stanno ricevendo benefici dal trattamento in studio possono continuare la terapia sperimentale anche dopo il database lock. |
|
| 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 |
| E.8.9.2 | In all countries concerned by the trial years | 5 |
| 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 |
Print
