A Phase I/II Trial Testing Nelfinavir, an Inhibitor of Akt Signaling, in Combination With Preoperative Chemoradiotherapy in Patients With Locally Advanced Rectal Cancer
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Enrollment
- 15
- Locations
- 1
- Primary Endpoint
- phase I: Incidence of any grade 3 or higher non-hematological or grade 4 or higher hematological toxicity (CTCAE v3.0) and of grade 4 or higher postoperative toxicity within 30 days post-surgery phase II:rate of pathological complete remission
Study Overview
Brief Summary
The aim is to study safety and activity of nelfinavir , added to standard chemoradiotherapy in patients with locally advanced rectal cancer. Furthermore analysis of the effect of nelfinavir combined with chemoradiation on tumour tissue will be studied
Detailed Description
Objective of the study:
The aim is to study safety and activity of nelfinavir, added to standard chemoradiotherapy (28x1.8 Gy and capecitabine 825 mg/m2 BID) in patients with locally advanced rectal cancer. Furthermore analysis of the effect of nelfinavir combined with chemoradiation on tumor tissue will be studied.
Study design:
This is an open label, single-center phase I/II trial. During phase I the toxicity of 2 dose levels will be studied (750 mg BID and 1250 mg BID). During phase II the activity of nelfinavir in combination with capecitabine and radiotherapy will be studied, using the MTD from phase I. With respect to translational research, phosphorylation of Akt in monocytes and tumorcells will be measured at different timepoints during treatment. Furthermore, dynamic CT-PET scans will be obtained at different time points to get an impression of changes in SUV and perfusion during treatment and to correlate these changes with pathological response.
Study population:
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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 = or < 3x normal
- •ASAT and ALAT = or < 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
Arms & Interventions
nelfinavir
see intervention
Intervention: nelfinavir (Drug)
Outcomes
Primary Outcomes
phase I: Incidence of any grade 3 or higher non-hematological or grade 4 or higher hematological toxicity (CTCAE v3.0) and of grade 4 or higher postoperative toxicity within 30 days post-surgery phase II:rate of pathological complete remission
Time Frame: 22 wks
Secondary Outcomes
No secondary outcomes reported