Sutent and Radiation as Treatment for Limited Extent Metastatic Cancer

Study Overview
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Brief Summary
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Cancer is the second leading cause of death in the United States, with approximately 90% of deaths resulting from patients with metastatic spread. Save for notable exceptions such as testicular cancer, chemotherapy alone cannot cure patients with metastases. Some patients with limited metastatic deposits (most commonly colon cancer spread to the liver) can be cured with surgery followed by chemotherapy. Therefore, some patients with metastases should be considered for aggressive local therapy (surgery and/or radiation). Even though chemotherapy has improved significantly, patients treated with conventional chemotherapy and/or biologically targeted therapy are not cured of their disease. For the most common types of cancer, chemotherapy alone can shrink or stabilize tumors for an average of 6 months before the tumors regrow. Both chemotherapy and biologically targeted therapy have major limitations preventing cure of these patients. Radiation therapy is an effective modality of treating cancer. Until recently, radiation for metastases was used only to relieve symptoms resulting from local tumor growth. Technological advances, including stereotactic radiotherapy, allow for radiation to be more precisely delivered to the tumor while sparing nearby normal organs. Stereotactic radiotherapy can completely eradicate local tumors with minimal side effects. Stereotactic radiotherapy has never been combined with drug therapy. Sutent is a new F.D.A. approved cancer therapy that targets tumor blood vessels. It is effective against two types of cancer that rarely respond to chemotherapy (GI stromal tumors and kidney cancer). We propose combining biologically targeted drug therapy with physically targeted stereotactic radiotherapy. Our goal is to determine if this is a safe regimen and the best method of combining these treatments. Ultimately, our goal is to cure some patients with previously incurable metastatic cancer with this combination.

Official Title
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Phase I/II Study of Stereotactic Radiation Therapy and Concurrent and Adjuvant Sutent (SU11248) as Treatment for Oligometastatic Disease

Conditions
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Cancer

Intervention / Treatment
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* Drug: sunitinib malate (Sutent)
* Procedure: radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Zubrod Performance Scale 0-1 Metastatic disease confirmed by biopsy or imaging 5 or fewer sites of metastatic disease on tumor staging (either CT chest/abdomen/pelvis plus bone scan or whole body FDG-PET) All tumors measure < 6 cm Age > 18 Chemotherapy must be completed at least 2 weeks prior to radiation Signed informed consent Adequate bone marrow function, defined as follows; Platelets > 100,000 cells/mm3 based upon CBC/differential obtained within 2 weeks prior to registration on study Absolute neutrophil count (ANC) > 1,800 cells/mm3 based on CBC/differential obtained within 2 weeks prior to registration on study Hemoglobin > 8.0 g/dl based upon CBC/differential obtained within 2 weeks prior to registration on study (Note: The use of transfusion or other intervention to achieve Hgb > 8.0 g/dt is acceptable.) Exclusion Criteria: Other coexisting malignancies or malignancies diagnosed within the previous 3 years with the exception of basal cell carcinoma, cervical carcinoma in situ, and other treated malignancies with no evidence of disease for at least 3 years Uncontrolled intercurrent illness including, but not limited to, ongoing active infection, symptomatic congestive heart failure (CHF), unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with the study requirements Patients with clinically significant pulmonary dysfunction, cardiomyopathy, or any history of clinically significant CHF are excluded. The exclusion of patients with active coronary heart disease will be at the discretion of the attending physician. Patients with exudative, bloody, or cytologically malignant effusions are not eligible. Pregnancy or breast feeding (Women of child-bearing potential are eligible, but must consent to using effective contraception during therapy and for at least 3 months after completing therapy) Patients must have no uncontrolled active infection other than that not curable without treatment of their cancer. Prior radiation to target area Patient may not be receiving any other investigational agents during radiotherapy. Prior history of non-inducible bleeding (12/16/09). Requirement for continuation of anticoagulation (defined as Coumadin, lovenox, heparin, plavix, aspirin, NSAIDs or similar drugs) during treatment (12/16/09) Under 18 years of age

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: Treatment<br>Participants treated with chemotherapy and radiotherapy | Drug: sunitinib malate (Sutent)<br>* Sutent administered PO QD from days 1 to 28 Two weeks after completion of any chemotherapy, maintenance Sutent in 6 week cycles (consisting of Sutent 50 mg PO QD weeks 1-4 followed by no treatment weeks 5-6) until progression or death If no chemotherapy is planned, maintenance Sutent (as described above) will start on day 43.<br>* Other names: Sutent;Procedure: radiotherapy<br>* Radiation is to be delivered to each site over 10 fractions separated by at least 16 hours. Up to 5 sites may be treated<br>* Other names: XRT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Dose Limiting Toxicity (DLT) | Sunitinib (SU) and radiation (IGRT) doses were sequentially escalated using a ping-pong strategy according to a 3 + 3 design phase 1 study. The starting dose was sunitinib 25 mg and IGRT 40 Gy. MTD reflects the highest dose that did not cause a dose limiting toxicity. Toxicity was in assessed in patients at regular intervals by using the Common Terminology Criteria for Adverse Events criteria (version 3.0). Dose limiting events were defined as any grade 4 or 5 toxicity and unexpected grade 3 toxicity. Expected grade 3 toxicities from radiation include mucositis or esophagitis lasting ≤7 days. Grade 3 metabolic and hematologic toxicities are considered expected events with sunitinib and therefore were not considered DLTs | 2 years | 
| Number of Participants With Particular Disease Status | Number of participants who have no evidence of disease and number of participants with distant metastases. | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients With Toxicity Grade 3 or Higher | % of patients experienced one or more grade ≥ 3 toxicities. Toxicity is graded as mild (Grade 1), moderate (Grade 2), severe (Grade 3), or life-threatening (Grade 4),and death (Grade 5). | 5 years | 
| Percentage of Patients With Local Control | Local control was defined as a tumor volume equal to or less than the tumor volume at start of radiotherapy. | 4 years | 
| Percentage of Patients With Distant Control | Distant control defined as distant metastasis contained outside of the radiation field within months of treatment. | 4 weeks | 
| Quality of Life |  | 4-6 weeks after radiation therapy | 
| Number of Participants According Failure and Survival |  | 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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erlotinib, celecoxib, radiation, progression-free survival