E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
A phase I/II trial testing nelfinavir, an inhibitor of Akt signaling, in combination with preoperative chemoradiotherapy with locally advanced rectal cancer |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10038050 |
E.1.2 | Term | Rectal cancer stage III |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10038051 |
E.1.2 | Term | Rectal cancer stage IV |
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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 |
2.1 Primary objective To investigate the safety and the activity of nelfinavir, administered before and during preoperative chemoradiotherapy, 28x1.8 Gy in combination with Xeloda 825 mg/m2 BID, in patients with locally advanced rectal carcinoma.
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E.2.2 | Secondary objectives of the trial |
2.2 Secondary Objectives • To describe the toxicity of the combined regimen studied. • To gain insight into the mechanism of interaction of this treatment combination by means of translational research.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Histologically proven adenocarcinoma of the rectum (tumor <15cm from anal verge) • Age >= 18 years • UICC T3-4 N0-2 M0 • WHO performance status 0-2 • Less than 10 % weight loss the last 6 months • No recent (< 3 months) severe cardiac disease (arrhythmia, congestive heart failure, infarction) • Normal serum bilirubin 3x normal • ASAT and ALAT 2,5x normal • creatinin clearance >50 ml/min • Willing and able to comply with the study prescriptions • No history of prior pelvic radiotherapy • No known HIV infection • No hemophilia • No concurrent medication that is metabolized by the CYP3A4 isoenzyme (calcium channel blockers, antifungal agents, macrolide antibiotics, gastrointestinal prokinetics, terfenadin, midazolam) • Statins should be stopped (except pravastatin and fluvastatin), • No concurrent use of St. John’s Wort (Hypericum perforatum) • Being willing and able to undergo one extra biopsy • Have given written informed consent before patient registration
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E.4 | Principal exclusion criteria |
The opposite of the above. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary end-point Incidence of any grade 3 or higher non-hematological or grade 4 or higher hematological toxicity (according to CTCAE v3.0) and incidence of grade 4 or higher postoperative toxicity within 30 days post-surgery (see chapter 5).
Secondary end-points 1. The rate of pathological Complete Remission (pCR) 2. Histopathologic negative circumferential resection margin (CRM) rate 3. Local and distance recurrence rate 4. Progression free and overall survival 5. Metabolic Response rate at CT-PET at time of surgery 6. Phosphorylation of Akt in the tumor at 3 different time points (chapter 9) 7. Tumor perfusion assessed by dynamic CT-scan (chapter 9)
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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 | No |
E.6.4 | Safety | No |
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 | 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 | 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 | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
E.8.5 | The trial involves multiple Member States | Information not present in EudraCT |
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 | 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
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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 | 2 |