Sutent and Radiation as Treatment for Limited Extent Metastatic Cancer

Phase 1

Completed

Conditions: Cancer

Interventions: Drug: sunitinib malate (Sutent)
Procedure: radiotherapy

Registration Number: NCT00463060

Lead Sponsor: Icahn School of Medicine at Mount Sinai

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 47

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;
1. Platelets > 100,000 cells/mm3 based upon CBC/differential obtained within 2 weeks prior to registration on study
2. Absolute neutrophil count (ANC) > 1,800 cells/mm3 based on CBC/differential obtained within 2 weeks prior to registration on study
3. 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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment	sunitinib malate (Sutent)	Participants treated with chemotherapy and radiotherapy
Treatment	radiotherapy	Participants treated with chemotherapy and radiotherapy

Primary Outcome Measures

Name	Time	Method
Number of Participants With Particular Disease Status	5 years	Number of participants who have no evidence of disease and number of participants with distant metastases.
Number of Participants With Dose Limiting Toxicity (DLT)	2 years	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

Secondary Outcome Measures

Name	Time	Method
Quality of Life	4-6 weeks after radiation therapy
Percentage of Patients With Distant Control	4 weeks	Distant control defined as distant metastasis contained outside of the radiation field within months of treatment.
Percentage of Patients With Local Control	4 years	Local control was defined as a tumor volume equal to or less than the tumor volume at start of radiotherapy.
Percentage of Patients With Toxicity Grade 3 or Higher	5 years	% 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).
Number of Participants According Failure and Survival	4 years