Nelfinavir, a Phase I/Phase II Rectal Cancer Study (Nelfinavir)

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

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

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer; Colorectal Tumors; Colorectal Carcinoma; Neoplasms, Colorectal
• Intervention / Treatment: Drug: nelfinavir

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.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Maastricht, Netherlands, 6229 ET
    • Maastro clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: nelfinavir; see intervention

Drug: nelfinavir; Phase I: take nelfinavir tablets (minimum 6, maximum 10) starting 7 days before start of chemoradiotherapy, for 45 days; day 0 and day 7 and week 2-3-4-5-6-7 weekly blood sample; day 0: PET-CT Phase II: take nelfinavir tablets (MTD from phase 1) starting 7 days before start of chemoradiotherapy, for 45 days; day 0 and day 7 and week 2-3-4-5-6-7 weekly blood sample; day 7 biopsy; day 7, 21 and week 15 :PET-CT + perfusion CT; Other Names: Viracept

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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	22 wks

Collaborators and Investigators

• Sponsor: Maastricht Radiation Oncology
• Investigators: Principal Investigator: Ph. Lambin, MD PhD, Maastro Clinic, The Netherlands

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (Actual): September 1, 2010
• Study Completion (Actual): July 1, 2013

Study Registration Dates

• First Submitted: June 23, 2008
• First Submitted That Met QC Criteria: June 24, 2008
• First Posted (Estimate): June 25, 2008

Study Record Updates

• Last Update Posted (Estimate): December 8, 2014
• Last Update Submitted That Met QC Criteria: December 5, 2014
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Keywords: radiosensitivity; Locally advanced rectal cancer; chemoradiation; nelfinavir
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Nelfinavir
• Other Study ID Numbers: MEC 07-03-026