Nelfinavir, a Phase I/Phase II Rectal Cancer Study
Information source: Maastricht Radiation Oncology
Information obtained from ClinicalTrials.gov on October 04, 2010
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Colorectal Cancer; Colorectal Carcinoma; Colorectal Tumors; Neoplasms, Colorectal
Intervention: nelfinavir (Drug)
Phase: Phase 1/Phase 2
Status: Recruiting
Sponsored by: Maastricht Radiation Oncology Official(s) and/or principal investigator(s):
Ph. Lambin, MD PhD, Principal Investigator, Affiliation: MAASTRO Clinic
Overall contact:
J. Buijsen, MD, Phone: +31(0)884455666, Email: jeroen.buijsen@maastro.nl
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
Clinical Details
Official title: A Phase I/II Trial Testing Nelfinavir, an Inhibitor of Akt Signaling, in Combination With Preoperative Chemoradiotherapy in Patients With Locally Advanced Rectal Cancer
Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: 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
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:
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.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
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
Locations and Contacts
J. Buijsen, MD, Phone: +31(0)884455666, Email: jeroen.buijsen@maastro.nl
Maastro clinic, Maastricht 6229 ET, Netherlands; Recruiting
Jeroen Buijsen, MD, Phone: +31 (0) 884455666, Email: jeroen.buijsen@maastro.nl
Guido Lammering, MD, PhD, Phone: +31 (0) 884455666, Email: guido.lammering@maastro.nl
J. Buijsen, MD, Sub-Investigator
Philippe Lambin, MD, PhD, Principal Investigator
Guido Lammering, MD, PhD, Sub-Investigator
Additional Information
Starting date: September 2008
Last updated: May 14, 2010
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