Safety Study of Rapamycin Administered Before and During Radiotherapy to Treat Rectum Cancer

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Clinical Trial Testing Rapamycin, an mTOR-inhibitor, in Combination With Preoperative Radiotherapy in Operable Rectum Cancer: a Phase I and Phase II Study

Conditions
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Rectum Cancer

Intervention / Treatment
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* Drug: Rapamycin


Participation Criteria
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Eligibility Criteria
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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
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rapamycine<br>rapamycine 6 mg dd | Drug: Rapamycin<br>* dosis escalation: 2/4/6 mg rapamycin tablets, once daily during 13 days<br>* Other names: Sirolimus;|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Colorectal cancer, M-tor inhibitor, Rapamycin