Safety Study of Rapamycin Administered Before and During Radiotherapy to Treat Rectum Cancer - Full Text View

Sponsors and Collaborators:	Maastricht Radiation Oncology Academisch Ziekenhuis Maastricht
Information provided by:	Maastricht Radiation Oncology
ClinicalTrials.gov Identifier:	NCT00409994

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 I Phase II

MedlinePlus related topics: Cancer Radiation Therapy

Drug Information available for: Sirolimus

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Official Title:	A Clinical Trial Testing Rapamycin, an mTOR-Inhibitor, in Combination With Preoperative Radiotherapy in Operable Rectum Cancer: a Phase I and II Study

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 bij DCE-MRI [ Time Frame: within the first 6 weeks after surgery ] [ 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: within the first 6 weeks after surgery ] [ Designated as safety issue: No ]
Incidence of acute side effects of rapamycin, 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 ]

Estimated Enrollment:	65
Study Start Date:	September 2006
Estimated Study Completion Date:	August 2011
Estimated Primary Completion Date:	June 2011 (Final data collection date for primary outcome measure)

Intervention Details:

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

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 13 days (unless the optimal dose found in the phase I study is lower).

Preoperative radiotherapy (5x 5 Gy) will be administered at day 8-12, followed by TME-surgery at day 15.

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

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, Limburg
Maastricht Radiation Oncology	Recruiting
Maastricht, Limburg, Netherlands, 6202 AZ
Contact: Guido Lammering +31 (0) 88 44 55 666 guido.lammering@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:	MAASTRO clinic ( prof.dr. Ph. Lambin )
Study ID Numbers:	04-16
Study First Received:	December 11, 2006
Last Updated:	September 30, 2008
ClinicalTrials.gov Identifier:	NCT00409994 History of Changes
Health Authority:	Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Maastricht Radiation Oncology:

Colorectal cancer
M-tor inhibitor
Rapamycin

Study placed in the following topic categories:

Sirolimus
Digestive System Neoplasms
Immunologic Factors
Clotrimazole
Rectal Neoplasms
Gastrointestinal Diseases
Miconazole
Tioconazole
Rectal Neoplasm
Intestinal Diseases

Immunosuppressive Agents
Rectal Diseases
Intestinal Neoplasms
Anti-Bacterial Agents
Digestive System Diseases
Rectal Cancer
Antifungal Agents
Gastrointestinal Neoplasms
Colorectal Neoplasms

Additional relevant MeSH terms:

Sirolimus
Anti-Infective Agents
Digestive System Neoplasms
Immunologic Factors
Antineoplastic Agents
Rectal Neoplasms
Gastrointestinal Diseases
Physiological Effects of Drugs
Intestinal Diseases
Antibiotics, Antineoplastic
Immunosuppressive Agents

Rectal Diseases
Pharmacologic Actions
Intestinal Neoplasms
Anti-Bacterial Agents
Neoplasms
Neoplasms by Site
Digestive System Diseases
Antifungal Agents
Therapeutic Uses
Gastrointestinal Neoplasms
Colorectal Neoplasms

ClinicalTrials.gov processed this record on May 07, 2009