Dose Escalation of Hypofractionated Radiation Therapy in Patients With Metastatic Cancer

Study Overview
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Brief Summary
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Patients with metastatic cancer are generally treated with chemotherapy, which has improved median survival compared to best supportive care. Despite this, patients continue to have persistent disease at sites that were initially involved with cancer. Radiation therapy is an effective modality for treating localized cancer but generally has been only used for palliation of symptoms once a patient develops metastatic disease. Since patients often have persistent disease after chemotherapy, the goal of this trial is to use increasing doses of radiation therapy to all sites of involved disease in order to determine the safety and efficacy of hypofractionated radiation therapy. The purpose of this study is to establish a maximum tolerated dose, dose-limiting toxicities, and recommended phase 2 dose of hypofractionated radiation therapy.

Official Title
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A Study of Dose Escalation of Hypofractionated Radiation Therapy in Patients With Metastatic Cancer

Conditions
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Tumor, Cancer, Melanoma, Sarcoma, Carcinoma

Intervention / Treatment
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* Radiation: Hypofractionated RT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed diagnosis of cancer (including epithelial carcinoma, sarcoma, and melanoma) Age 18 years and older Life expectancy of > 3 months Patients with AJCC (6th edition, 2002) stage IV cancer with distant metastases and without pleural or pericardial effusion at diagnosis and before start of study Patients with 1-5 sites of maximum tumor dimension (for each individual site) of ≤ 10 cm or < 500 cc volume and amenable to radiation therapy as seen on standard imaging Unidimensionally measurable disease (based on RECIST) is desirable but not strictly required Brain metastases must have been treated prior to enrollment on study, preferably with stereotactic radiosurgery ECOG performance status ≤ 2 or Karnofsky Performance Status ≥ 60% No prior radiation therapy to currently involved tumor sites Room air saturation > 90% Hemoglobin > 9.0 g/dl ANC >=1,500/microliter Platelets >=100,000/microliter Total bilirubin within institutional limits Albumin > 2.9 g/dl Alkaline phosphatase < 2.5x upper limit of normal AST and ALT < 2.5 x upper limit of normal Ability to understand and willingness to sign a written informed consent document Exclusion Criteria: Uncontrolled intercurrent illness Patients with clinically significant pulmonary dysfunction, cardiomyopathy, or any history of clinically significant CHF are excluded. Exclusion of patients with active coronary heart disease will be at the discretion of the attending physician Patients with significant atelectasis such that CT definition of gross tumor volume is difficult to determine Pregnancy or breast feeding Patients must have no uncontrolled active infection other than that not curable with treatment of their cancer. Patients may not be receiving any other investigational drugs during RT

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: Radiation therapy<br> | Radiation: Hypofractionated RT<br>* RT to site of metastatic disease for three fractions separated by 3 to 8 days. Doses of radiation will increase as follows in order to determine the MTD in Gy: For all sites the dose levels are as follows: 8 Gy/ fraction x 3 fractions = 24 Gy 10 Gy/fraction x 3 fractions = 30 Gy 12 Gy/fraction x 3 fractions = 36 Gy 14 Gy/fraction x 3 fractions = 42 Gy 16 Gy/fraction x 3 fractions = 48 Gy 18 Gy/fraction x 3 fractions = 52 Gy 20 Gy/fraction x 3 fractions = 60 Gy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-limiting toxicities | The dose limiting toxicities occurring within the initial observation period will be defined. | 30-90 days | 
| maximum tolerated dose of hypofractionated RT |  | 30-90 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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solid tumor cancer, epithelial carcinoma