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

This study is ongoing, but not recruiting participants.
Academisch Ziekenhuis Maastricht
Information provided by (Responsible Party):
Maastricht Radiation Oncology Identifier:
First received: December 11, 2006
Last updated: January 27, 2016
Last verified: January 2016
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.

Condition Intervention Phase
Rectum Cancer
Drug: Rapamycin
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:

Further study details as provided by Maastricht Radiation Oncology:

Primary Outcome Measures:
  • Phase I: Incidence of severe postoperative complications (grade IV or grade V), [ Time Frame: within the first 6 weeks after surgery ] [ Designated as safety issue: Yes ]
  • assessed according to CTCv3.0 [ Time Frame: within the first 6 weeks after surgery ] [ Designated as safety issue: No ]
  • Phase II: Tumour blood flow assessed CT-PET + CTp [ Time Frame: day 64 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Phase I:Incidence of other acute toxicity, assessed according to CTCv 3.0 [ Time Frame: within the first 6 weeks after surgery ] [ Designated as safety issue: No ]
  • Activation status of mTor related and dependent molecules in the tumour [ Time Frame: within the first 6 weeks after surgery ] [ Designated as safety issue: No ]
  • Phase II:Maximum standardised Uptake Value (SUV) of 18F-FDG, assessed bij PET-CT-scan [ Time Frame: day 64 ] [ Designated as safety issue: No ]
  • Phase II:Incidence of acute side effects of rapamycin, assessed according to CTCv 4.0 [ Time Frame: day 8, 15, 22, 36, 50 and 64 ] [ Designated as safety issue: No ]

Estimated Enrollment: 65
Study Start Date: September 2006
Estimated Study Completion Date: August 2019
Estimated Primary Completion Date: August 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Rapamycine
rapamycine 6 mg dd
Drug: Rapamycin
dosis escalation: 2/4/6 mg rapamycin tablets, once daily during 13 days
Other Name: Sirolimus

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.


Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Histologically proven rectum cancer
  • 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
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Please refer to this study by its identifier: NCT00409994

Maastricht Radiation Oncology
Maastricht, Limburg, Netherlands, 6202 AZ
Sponsors and Collaborators
Maastricht Radiation Oncology
Academisch Ziekenhuis Maastricht
Principal Investigator: Guido Lammering Maastricht Radiation Oncology
  More Information

Responsible Party: Maastricht Radiation Oncology Identifier: NCT00409994     History of Changes
Other Study ID Numbers: 04-16 
Study First Received: December 11, 2006
Last Updated: January 27, 2016
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Maastricht Radiation Oncology:
Colorectal cancer
M-tor inhibitor

Additional relevant MeSH terms:
Rectal Neoplasms
Colorectal Neoplasms
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Neoplasms by Site
Rectal Diseases
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents
Immunologic Factors
Immunosuppressive Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses processed this record on April 27, 2016