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

Rectum Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00409994
• Other study ID #: 04-16
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: September 2006
• Est. completion date: December 2018

Study information

• Verified date: March 2019
• Source: Maastricht Radiation Oncology
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 44
• Est. completion date: December 2018
• Est. primary completion date: August 3, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Rectal Neoplasms
• Rectum Cancer

Intervention

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

Locations

Country	Name	City	State
Netherlands	Maastricht Radiation Oncology	Maastricht	Limburg

Sponsors (2)

Lead Sponsor	Collaborator
Maastricht Radiation Oncology	Academisch Ziekenhuis Maastricht

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase I: Incidence of severe postoperative complications (grade IV or grade V),		within the first 6 weeks after surgery
Primary	assessed according to CTCv3.0		within the first 6 weeks after surgery
Primary	Phase II: Tumour blood flow assessed CT-PET + CTp		day 64
Secondary	Phase I:Incidence of other acute toxicity, assessed according to CTCv 3.0		within the first 6 weeks after surgery
Secondary	Activation status of mTor related and dependent molecules in the tumour		within the first 6 weeks after surgery
Secondary	Phase II:Maximum standardised Uptake Value (SUV) of 18F-FDG, assessed bij PET-CT-scan		day 64
Secondary	Phase II:Incidence of acute side effects of rapamycin, assessed according to CTCv 4.0		day 8, 15, 22, 36, 50 and 64