A Phase I/II Trial Testing Nelfinavir, an Inhibitor of Akt Signaling, in Combination With Preoperative Chemoradiotherapy in Patients With Locally Advanced Rectal Cancer
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.
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
Patients with locally advanced rectal cancer, who are candidates for chemoradiotherapy. In
phase I, 6 patients will be included. In case of the occurrence of dose limiting toxicity,
extra patients will be included, according to the rules described in the protocol. In phase
II, 55 patients will be included.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
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
Ph. Lambin, MD PhD
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)