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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00704600
Recruitment Status : Completed
First Posted : June 25, 2008
Last Update Posted : December 8, 2014
Sponsor:
Information provided by (Responsible Party):
Maastricht Radiation Oncology

Study Description
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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

Condition or disease Intervention/treatment Phase
Colorectal Cancer Colorectal Carcinoma Colorectal Tumors Neoplasms, Colorectal Drug: nelfinavir Phase 1 Phase 2

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 Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 15 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : September 2008
Actual Primary Completion Date : September 2010
Actual Study Completion Date : July 2013

Resource links provided by the National Library of Medicine


Arms and Interventions
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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 Name: Viracept


Outcome Measures
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Primary Outcome Measures :
  1. 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 ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00704600


Locations
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Netherlands
Maastro clinic
Maastricht, Netherlands, 6229 ET
Sponsors and Collaborators
Maastricht Radiation Oncology
Investigators
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Principal Investigator: Ph. Lambin, MD PhD Maastro Clinic, The Netherlands
More Information
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Responsible Party: Maastricht Radiation Oncology
ClinicalTrials.gov Identifier: NCT00704600    
Other Study ID Numbers: MEC 07-03-026
First Posted: June 25, 2008    Key Record Dates
Last Update Posted: December 8, 2014
Last Verified: December 2014
Keywords provided by Maastricht Radiation Oncology:
Locally advanced rectal cancer
nelfinavir
radiosensitivity
chemoradiation
Additional relevant MeSH terms:
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Colorectal Neoplasms
Rectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
 Rectal Diseases
Nelfinavir
HIV Protease Inhibitors
Viral Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents