E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
advanced adenocarcinoma of the rectum |
|
E.1.1.1 | Medical condition in easily understood language |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
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 |
Phase I part of the trial: define the safe dose of infusional 5-FU in combination with Cetuximab and RT in this
setting
Phase II part of the trial: Assessment of the pathological complete response (pCR) |
|
E.2.2 | Secondary objectives of the trial |
Assessment of treatment related toxicities
Assessment of the frequency of sphincter-preserving surgery
Assessment of R0-resection rate
Assessment of overall pathological response rate (pCR + pPR)
Assessment of Recurrence of disease in FU
E. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Signed written informed consent
• Male or female > 18 years of age
• Histologically proven locally advanced adenocarcinoma of the rectum (T3, T4, any nodal stage) with the
inferior margin of the tumor being no farther than 16 cm from the anal verge
• Surgical resectability or possible sphincter preservation after neoadjuvant treatment
• ECOG Performance Status < 2
• Adequate bone marrow function: leucocytes > 3.0 x 109/L, neutrophils > 1.5 x 109/L, platelets > 100 x 109/L,
hemoglobin > 10.0 g/dL
• Adequate liver function: Bilirubin < 2.0 mg/dL, SGOT, SGPT, AP, gamma-GT < 3 x ULN
• Adequate renal function: serum creatinine < 1.5 mg/dL, creatinine clearance > 50 ml/min (calculated value
according to Cockroft-Gault equation)
• If of childbearing potential, willingness to use effective contraceptive method for an adequate period of time. |
|
E.4 | Principal exclusion criteria |
• Prior pelvic radiotherapy
• Prior chemotherapy
• Presence of distant metastases
• Clinically relevant coronary artery disease or a history of myocardial infarction within the last 12 months or left
ventricular ejection fraction (LVEF) below the institutional range of normal
• Other chronic bowel disease (malabsorption, inflammatory bowel disease, acute or subacute intestinal
occlusion)
• Prior exposure to EGFR pathway targeting therapy
• Having participated in another clinical trial or any investigational agent in the preceding 30 days
• Any active dermatological condition > Grade 1
• Known allergic/hypersensitivity reaction to any of the components of the treatment
• Pregnancy (absence confirmed by serum/urine �-HCG) or breast-feeding
• Known drug abuse/alcohol abuse
• Other previous malignancy within 5 years, with exception of a history of a previous basal cell carcinoma of the
skin or pre-invasive carcinoma of the cervix
• Legal incapacity or limited legal capacity
• Medical or psychological condition which in the opinion of the investigator would not permit the patient to
complete the study or sign meaningful informed consent |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Within the phase I part of the trial, the Dose-Limiting Toxicity is the primary safety parameter.
For quantification of efficacy within the second part of the trial, the primary objective is the pathological
response, defined as complete response as determined by the pathologist at surgery. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
DLT are assessed from treatment start (day 1) until 10 days following completion of
radiochemotherapy (= day 48).
For quantification of efficacy within the second part of the trial, the primary objective is the pathological
response, defined as complete response as determined by the pathologist at surgery. |
|
E.5.2 | Secondary end point(s) |
Assessment of treatment related toxicities
Assessment of the frequency of sphincter-preserving surgery
Assessment of R0-resection rate
Assessment of overall pathological response rate (pCR + pPR)
Assessment of Recurrence of disease in FU |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Treatment phase and / or Follow-Up phase |
|
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) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
safe dose of infusional 5-FU in combination with Cetuximab and RT |
|
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 0 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
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
|
The end of trial is defined as the end FU of the last patient |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 8 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 8 |
E.8.9.2 | In all countries concerned by the trial months | 0 |