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

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

Status

Completed

Phases

Phase 1Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00409994

Enrollment

Registered

2006-12-12

Start date

2006-09-30

Completion date

2018-12-31

Last updated

2019-03-18

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Rectum Cancer

Keywords

Colorectal cancer, M-tor inhibitor, Rapamycin

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.

Interventions

DRUGRapamycin

dosis escalation: 2/4/6 mg rapamycin tablets, once daily during 13 days

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Healthy volunteers

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

Design outcomes

Primary

Measure	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

Measure	Time frame
Phase I:Incidence of other acute toxicity, assessed according to CTCv 3.0	within the first 6 weeks after surgery
Phase II:Incidence of acute side effects of rapamycin, assessed according to CTCv 4.0	day 8, 15, 22, 36, 50 and 64
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

Countries

Netherlands

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026