Overview

This trial is active, not recruiting.

Condition rectum cancer
Treatment rapamycin
Phase phase 1/phase 2
Targets mTOR, FKBP-12
Sponsor Maastricht Radiation Oncology
Collaborator Academisch Ziekenhuis Maastricht
Start date September 2006
End date August 2018
Trial size 65 participants
Trial identifier NCT00409994, 04-16

Summary

Investigating the safety and the activity of Rapamycin, administered before and during preoperative radiotherapy in patients with an operable colorectal carcinoma. The phase I dose escalation study will be performed in three steps (2, 4 and 6 mg). Patients entered in phase II will follow the same tolerable treatment regimen as patients in phase I study.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
rapamycine 6 mg dd
rapamycin Sirolimus
dosis escalation: 2/4/6 mg rapamycin tablets, once daily during 13 days

Primary Outcomes

Measure
Phase I: Incidence of severe postoperative complications (grade IV or grade V),
time frame: within the first 6 weeks after surgery
assessed according to CTCv3.0
time frame: within the first 6 weeks after surgery
Phase II: Tumour blood flow assessed CT-PET + CTp
time frame: day 64

Secondary Outcomes

Measure
Phase I:Incidence of other acute toxicity, assessed according to CTCv 3.0
time frame: within the first 6 weeks after surgery
Activation status of mTor related and dependent molecules in the tumour
time frame: within the first 6 weeks after surgery
Phase II:Maximum standardised Uptake Value (SUV) of 18F-FDG, assessed bij PET-CT-scan
time frame: day 64
Phase II:Incidence of acute side effects of rapamycin, assessed according to CTCv 4.0
time frame: day 8, 15, 22, 36, 50 and 64
Activation status of mTOR related and dependent molecules in the tumour
time frame: within the first 6 weeks after surgery

Eligibility Criteria

Male or female participants of any age.

Inclusion Criteria: - Histologically proven rectum cancer - UICC TNM I-III - WHO performance status 0-2 - Less than 10% weight loss the last 6 months - No recent (< 3 months) severe cardiac disease - Normal serum bilirubin and serum creatinin Exclusion Criteria: - Concurrent chemotherapy with radiation - History of prior pelvis radiotherapy - Recent (<3 months) myocardial infarction - Uncontrolled infectious disease - Concurrent medication known as inhibitors of CYP3A4 susceptible to increase Rapamycin blood concentrations

Additional Information

Official title A Clinical Trial Testing Rapamycin, an mTOR-inhibitor, in Combination With Preoperative Radiotherapy in Operable Rectum Cancer: a Phase I and Phase II Study
Principal investigator Guido Lammering
Description Treatment regimen Phase I A daily dose of Rapamycin will be taken during 13 days. At step 1 a dose of 2 mg will be given once a day; at step 2 a dose of 4 mg will be given once a day; at step 3 a dose of 6 mg will be given once a day. Preoperative radiotherapy (5x 5 Gy) will be administered at day 8-12, followed by TME-surgery at day 15. Phase II A daily dose of 6 mg Rapamycin will be taken for 14 days (unless the optimal dose found in the phase I study is lower). Preoperative radiotherapy (5x 5 Gy) will be administered at day 9-15, followed by TME-surgery 7-8 weeks post RT. Sample size Phase I dose-escalation study Minimum 3 eligible patients per step, maximum 6 eligible patients per step. Phase II A total of 47 patients will be entered in this part of the study.
Trial information was received from ClinicalTrials.gov and was last updated in December 2014.
Information provided to ClinicalTrials.gov by Maastricht Radiation Oncology.