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

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Maastricht Radiation Oncology
Sponsor:
Collaborator:
Academisch Ziekenhuis Maastricht
Information provided by (Responsible Party):
Maastricht Radiation Oncology
ClinicalTrials.gov Identifier:
NCT00409994
First received: December 11, 2006
Last updated: March 20, 2014
Last verified: March 2014
  Purpose

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 ]
  • 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 ]

Estimated Enrollment: 65
Study Start Date: September 2006
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: November 2014 (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.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00409994

Contacts
Contact: Philippe Lambin, Prof, MD PHD +31 (0) 88 44 55 666 philippe.lambin@maastro.nl
Contact: Guido Lammering, MD PhD =31 (0) 88 44 55 666 guido.lammering@maastro.nl

Locations
Netherlands
Maastricht Radiation Oncology Recruiting
Maastricht, Limburg, Netherlands, 6202 AZ
Contact: Jeroen Buijsen    +31 (0) 88 44 55 666    jeroen.buijsen@maastro.nl   
Contact: Jos Jager    +31 (0) 88 44 55 666    jos.jager@maastro.nl   
Principal Investigator: Guido Lammering         
Sponsors and Collaborators
Maastricht Radiation Oncology
Academisch Ziekenhuis Maastricht
Investigators
Principal Investigator: Guido Lammering Maastricht Radiation Oncology
  More Information

No publications provided

Responsible Party: Maastricht Radiation Oncology
ClinicalTrials.gov Identifier: NCT00409994     History of Changes
Other Study ID Numbers: 04-16
Study First Received: December 11, 2006
Last Updated: March 20, 2014
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

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

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

ClinicalTrials.gov processed this record on August 28, 2014