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A Phase I/II Trial Testing Nelfinavir, an Inhibitor of Akt Signaling, in Combination With Preoperative Chemoradiotherapy in Patients With Locally Advanced Rectal Cancer

Phase 1/Phase 2
18 Years
Open (Enrolling)
Colorectal Cancer, Colorectal Carcinoma, Colorectal Tumors, Neoplasms, Colorectal

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Trial Information

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.

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.

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,

- 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

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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

Outcome Time Frame:

22 wks

Safety Issue:


Principal Investigator

Ph. Lambin, MD PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:



Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Study ID:

MEC 07-03-026



Start Date:

September 2008

Completion Date:

September 2012

Related Keywords:

  • Colorectal Cancer
  • Colorectal Carcinoma
  • Colorectal Tumors
  • Neoplasms, Colorectal
  • Locally advanced rectal cancer
  • nelfinavir
  • radiosensitivity
  • chemoradiation
  • Neoplasms
  • Carcinoma
  • Rectal Neoplasms
  • Colorectal Neoplasms