Nelfinavir, a Phase I/Phase II Rectal Cancer Study

The recruitment status of this study is unknown because the information has not been verified recently.
Verified April 2012 by Maastricht Radiation Oncology.
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by:
Maastricht Radiation Oncology
ClinicalTrials.gov Identifier:
NCT00704600
First received: June 23, 2008
Last updated: April 19, 2012
Last verified: April 2012
  Purpose

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 Intervention Phase
Colorectal Cancer
Colorectal Carcinoma
Colorectal Tumors
Neoplasms, Colorectal
Drug: nelfinavir
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Maastricht Radiation Oncology:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 55
Study Start Date: September 2008
Estimated Study Completion Date: September 2012
Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00704600

Locations
Netherlands
Maastro clinic
Maastricht, Netherlands, 6229 ET
Sponsors and Collaborators
Maastricht Radiation Oncology
Investigators
Principal Investigator: Ph. Lambin, MD PhD Maastro Clinic, The Netherlands
  More Information

No publications provided

Responsible Party: P. Lambin MD PhD, Maastro clinic
ClinicalTrials.gov Identifier: NCT00704600     History of Changes
Other Study ID Numbers: MEC 07-03-026
Study First Received: June 23, 2008
Last Updated: April 19, 2012
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Maastricht Radiation Oncology:
Locally advanced rectal cancer
nelfinavir
radiosensitivity
chemoradiation

Additional relevant MeSH terms:
Neoplasms
Carcinoma
Rectal Neoplasms
Colorectal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Colonic Diseases
Nelfinavir
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 26, 2014