E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
metastatic colorecal cancer |
cancro del colon-retto metastatico |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 14.1 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10017947 |
E.1.2 | Term | Gastrointestinal disorders |
E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
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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 |
To determine the 6 month PFS benefit of cetuximab alone or in combination with irinotecan in patients with KRAS WT or KRAS G13D mutated mCRC (PFS defined from time of randomisation to disease progression as defined by RECIST criteria version 1.1). |
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E.2.2 | Secondary objectives of the trial |
Response rate by RECIST v1.1. criteria |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Histologic or cytologic diagnosis of adenocarcinoma of the gallbladder or intra/extrahepatic bile ducts with locally advanced or metastatic disease (at study entry) that is not amenable to curative surgical resection or with recurrent disease after prior surgical resection or radiotherapy; 2.K-RAS wild-type oncogene; 3.Uni-dimensional measurable disease as assessed by CT scan (RECIST v1.1 criteria). 4.Patients must have received no prior chemotherapy or biological therapy for advanced disease; 5.Prior radiotherapy must be completed at least 4 weeks before study enrolment. Patients must have recovered from the acute toxic effects of the treatment prior to study enrolment; 6.WHO performance status 0, 1 or 2; 7.Estimated life expectancy of at least 12 weeks; 8.Patient compliance and geographic proximity that allows adequate follow-up; 9.Adequate organ function including the following: a.Adequate bone marrow reserve: absolute neutrophil count (ANC) of greater than or equal to 1.5 x109/L, platelet count of greater than or equal to 100 x109/L, and haemoglobin of greater than or equal to 9 g/dL. b.Hepatic: AST and ALT less than 5 x upper limit of normal (ULN); bilirubin less than 2 x ULN; in patients with obstructive jaundice and bilirubin greater than or equal 2 x ULN, internal or external biliary drainage should be performed before enrollment. Patients should be enrolled only if bilirubin declines to greater than or equal 2 x ULN. c.Renal: creatinine less than 1. 5 x ULN and calculated creatinine clearance greater than or equal to 50 mL/min, calculated according to the Cockcroft formula. 10.Signed informed consent from patient or legal representative. 11.Patients available to complete study requirements (visits, tests, evaluations and follow-up procedures) in a timely manner. 12.Male and female patients with reproductive potential must use a reliable contraceptive method if appropriate (eg, intrauterine device [IUD], birth control pills, or barrier device) during and for 3 months after the study. Females with childbearing potential must have a negative urine pregnancy test within 7 days prior to study enrolment. |
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E.4 | Principal exclusion criteria |
1.Medical or psychiatric conditions that compromise the patient’s ability to give informed consent or comply with the study protocol; 2.Heart failure, angina pectoris or arrhythmia that are poorly controlled in spite of medication or acute myocardial infarction within 6 months preceding study enrollment; 3.Active infection that in the opinion of the investigator would compromise the patient’s ability to tolerate therapy, especially uncontrolled biliary tract infections; 4.Poorly controlled diabetes mellitus; 5.Interstitial lung disease 6.Any other serious concomitant disorders that would compromise the safety of the patient or compromise the patient’s ability to complete the study, at the discretion of the investigator; 7.Pregnancy or breast feeding or unwilling / unable to practice adequate contraception 8.Second primary malignancy (except in situ carcinoma of the cervix or adequately treated non-melanomatous carcinoma of the skin or other malignancy treated at least 5 years previously with no evidence of recurrence) 9.Pregnancy or breast feeding or unwilling / unable to practice adequate contraception. 10.Documented brain metastasis. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Objective clinical benefit (combined rates of documented CR, PR and SD), PFS |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
A tumour responder is defined as any patient exhibiting a best study response of CR or PR (based on CT or MRI) as per RECIST v1.1. Scans taken every 6weeks from baseline
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E.5.2 | Secondary end point(s) |
(progression free survival), TTF (time to tretment failure), OS (overall survival), duration of the response |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Time to treatment failure is defined as the time from the date of study enrolment to the date of the first of the following events: early discontinuation of study therapy, progression of disease, or death due to any cause. |
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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 | Yes |
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 | 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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 3 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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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
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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 | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |