A phase I/II trial testing nelfinavir, an inhibitor of Akt signaling, in combination with preoperative chemoradiotherapy in patients with locally advanced rectal cancer

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 61

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)
• 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)
• Women should not be pregnant or lactating
• Being willing and able to undergo one extra biopsy
• Have given written informed consent before patient registration

Exclusion Criteria

the opposite of the above

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Phase I: incidence of any grade 3 or higher non-hematological or grade 4 or<br /><br>higher hematological toxicity and incidence of grade 4 or higher postoperative<br /><br>toxicity within 30 days post-surgery<br /><br>Phase II: the rate of pathological complete remission (pCR)</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>- Progression free and overall survival<br /><br>- Local and distant recurrence rate<br /><br>- Metabolic response rate on CT-PET at time of surgery<br /><br>- Phosphorylation of Akt in the tumor at different time points<br /><br>- Tumor perfusion assessed by dynamic CT-scan</p><br>