Evaluation of Low-dose Irinotecan and Cyberknife® SBRT to Treat Colorectal Cancer With Limited Liver Metastasis

Study Overview
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Brief Summary
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The purpose of this study is to determine the effects of CyberKnife stereotactic body radiotherapy in combination with irinotecan chemotherapy in patients with colon or rectal cancer that has spread to the liver. Conventional radiation therapy has a limited role in the treatment of patients with liver metastases because the radiation doses are limited by liver toxicity. The CyberKnife system is a type of radiation machine that precisely focuses large doses of x-rays on the tumor, so that injury from radiation to the nearby normal tissue will be minimal. It is approved by the U.S. Food and Drug Administration to treat tumors, lesions and conditions anywhere in the body when radiation therapy is required. While the device is no longer classified as investigational, the best treatment dose and times are still being evaluated. Chemotherapy delivered with radiation therapy can increase the effectiveness of treatment, and may allow for a lower dose of radiation therapy to be utilized, thereby limiting negative side effects. In this study, patients will receive Cyberknife radiosurgery directed to liver metastasis for 3-5 treatments, given every other day. Irinotecan 40mg/m2 will be administered intravenously daily for 3-5 days (5 treatments within 10 elapsed days), and prior to radiation therapy. Patients will have follow-up visits at months 1,2,4,6,9,12,15,18, 24, 30, 36, and every 6 months thereafter for 3 years.

Official Title
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Prospective Evaluation of Low-dose Irinotecan and Cyberknife® Stereotactic Body Radiotherapy in the Treatment of Patients With Colorectal Cancer and Limited Liver Metastasis

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: Irinotecan
* Radiation: CyberKnife


Participation Criteria
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Eligibility Criteria
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Age>18 years Histologically confirmed primary colorectal cancer Stage IV colorectal cancer with </= 3 metastases, up to 5cm in size. CT scan or MRI of the abdomen with contrast, 60days prior to enrollment If patient is allergic to contrast, imaging without contrast is acceptable Positron-Emission Tomography 60 days prior to enrollment No additional sites of metastasis at the time of protocol enrollment. History of other sites of metastasis that are currently controlled are acceptable. No malignant ascites At least 4 weeks from any chemotherapy No prior liver radiation therapy ECOG performance status 0-1 Life expectancy>3months Laboratory evaluations completed 60 days prior to treatment including CMP, CBC with differential, liver function test, and prothrombin time.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low-Dose Irinotecan & CyberKnife SBRT<br>Irinotecan 40mg/m2 x 3-5 days + CyberKnife SBRT 45-60Gy x 3-5 fractions | Drug: Irinotecan<br>* 40mg/m2 x 3-5 days<br>* Other names: CPT-11;Radiation: CyberKnife<br>* 45-60 Gy for 3-5 days CyberKnife SBRT to liver metastasis within 10 elapsed days. Irinotecan will be administered on the same day, prior to SBRT.<br>* Other names: Stereotactic Radiosurgery;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events related to toxicities from concurrent SBRT and irinotecan |  | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor response rate |  | 3 years | 
| Progression free survival |  | 3 years | 
| Overall survival |  | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stage IV Colorectal Carcinoma, Liver metastasis, Cyberknife, Stereotactic Body Radiotherapy, SBRT, Irinotecan HCl, CPT-11