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

Phase 1

Completed

• Conditions: Rectum Cancer
• Interventions: Drug: Rapamycin

• Registration Number: NCT00409994
• Lead Sponsor: Maastricht Radiation Oncology

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.

Study Timeline

• Study Start: 2006-09
• Study First Submitted: 2006-12-11
• Study First Submitted QC: 2006-12-11
• Study First Posted: 2006-12-12
• Primary Completion: 2018-08-03
• Study Completion: 2018-12
• Status Verified: 2019-03
• Last Update Submitted: 2019-03-14
• Last Update Posted: 2019-03-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 44

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Rapamycine	Rapamycin	rapamycine 6 mg dd

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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

Trial Locations

Locations (1)

Maastricht Radiation Oncology; 🇳🇱 Maastricht, Limburg, Netherlands