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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00409994
Recruitment Status : Active, not recruiting
First Posted : December 12, 2006
Last Update Posted : March 22, 2017
Academisch Ziekenhuis Maastricht
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Rectum Cancer Drug: Rapamycin Phase 1 Phase 2

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 Type : Interventional  (Clinical Trial)
Estimated Enrollment : 65 participants
Intervention Model: Single Group Assignment
Masking: None (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
Study Start Date : September 2006
Estimated Primary Completion Date : August 2018
Estimated Study Completion Date : August 2019

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Rapamycine
rapamycine 6 mg dd
Drug: Rapamycin
dosis escalation: 2/4/6 mg rapamycin tablets, once daily during 13 days
Other Name: Sirolimus

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

Secondary Outcome Measures :
  1. Phase I:Incidence of other acute toxicity, assessed according to CTCv 3.0 [ Time Frame: within the first 6 weeks after surgery ]
  2. Activation status of mTor related and dependent molecules in the tumour [ Time Frame: within the first 6 weeks after surgery ]
  3. Phase II:Maximum standardised Uptake Value (SUV) of 18F-FDG, assessed bij PET-CT-scan [ Time Frame: day 64 ]
  4. 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 ]

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00409994

Maastricht Radiation Oncology
Maastricht, Limburg, Netherlands, 6202 AZ
Sponsors and Collaborators
Maastricht Radiation Oncology
Academisch Ziekenhuis Maastricht
Principal Investigator: Jeroen Buijsen, MD PhD Maastricht Radiation Oncology

Responsible Party: Maastricht Radiation Oncology Identifier: NCT00409994     History of Changes
Other Study ID Numbers: 04-16
First Posted: December 12, 2006    Key Record Dates
Last Update Posted: March 22, 2017
Last Verified: March 2017

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

Additional relevant MeSH terms:
Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs