Clinical trial NCT00409994: Safety Study of Rapamycin Administered Before and During Radiotherapy to Treat Rectum Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Rectum Cancer
Keywords: Colorectal cancer
M-tor inhibitor
Rapamycin
Lead sponsor: Maastricht Radiation Oncology
Sponsor class: OTHER
Collaborators: name: Academisch Ziekenhuis Maastricht
First posted: 2006-12-12
Enrollment: 44
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Phase I: Incidence of severe postoperative complications (grade IV or grade V),
timeFrame: within the first 6 weeks after surgery
measure: assessed according to CTCv3.0
timeFrame: within the first 6 weeks after surgery
measure: Phase II: Tumour blood flow assessed CT-PET + CTp
timeFrame: day 64
Secondary outcomes:
measure: Phase I:Incidence of other acute toxicity, assessed according to CTCv 3.0
timeFrame: within the first 6 weeks after surgery
measure: Activation status of mTor related and dependent molecules in the tumour
timeFrame: within the first 6 weeks after surgery
measure: Phase II:Maximum standardised Uptake Value (SUV) of 18F-FDG, assessed bij PET-CT-scan
timeFrame: day 64
measure: Phase II:Incidence of acute side effects of rapamycin, assessed according to CTCv 4.0
timeFrame: day 8, 15, 22, 36, 50 and 64
Other outcomes:
Locations:
city: Maastricht
country: Netherlands
facility: Maastricht Radiation Oncology
state: Limburg
Study officials:
affiliation: Maastricht Radiation Oncology
name: Jeroen Buijsen, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: