A Randomized Trial Evaluating Rapid Delivery of Dose Escalated Hypofractionated Radiotherapy for Patients Diagnosed With Bone Metastases for Effective Palliation of Symptoms

Study Overview
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Brief Summary
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The goal of this clinical research study is to learn if 1 large dose of radiation therapy is better at controlling pain from cancer that has spread to the bones than 10 smaller doses of radiation. Researchers also want to learn if 1 large dose of radiation therapy can help decrease the use of drugs to control the pain, and if it can help to control the disease.

Detailed Description
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Study Groups: If you are found to be eligible to take part in this study, you will be randomly assigned (as in the flip of a coin) to 1 of 2 study groups. This is done because no one knows if one study group is better, the same, or worse than the other group. You will have an equal chance of being assigned to either group. If you are in Group 1, you will receive 1 radiation treatment a day for 10 days in a row (not counting weekends or holidays). You will receive a higher total dose of radiation than Group 2. If you are in Group 2, you will receive 1 radiation treatment given on 1 day. Radiation Therapy: You will lie on a table for the radiation treatment(s). Each treatment will last about 30 minutes. Length of Treatment: You may receive 1 or 10 radiation treatments, depending on which group you are in. You will no longer be able to receive radiation therapy if intolerable side effects occur or if you are unable to follow study directions. Your participation on the study will be over after the follow-up visits. Follow-Up Visits: At Months 3, 6, 9, 12 and every 3 to 6 months after the start of radiation therapy, you will have x-rays, a bone scan, CT scan, or MRI to check the status of the disease. At Months 3, 4, and 6 and then every 3 months after that for at least 3 years, you will complete the questionnaires about the pain, your pain relief, and your quality of life. The questionnaires can be filled out at a clinic visit or sent back in the mail. This is an investigational study. Radiation therapy is delivered using FDA-approved and commercially available methods. It is investigational to compare the number and size of radiation doses. Up to 300 participants will take part in this multicenter study. Up to 300 participants will be enrolled at MD Anderson.

Official Title
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A Randomized Trial Evaluating Rapid Delivery of Dose Escalated Hypofractionated Radiotherapy for Patients Diagnosed With Bone Metastases for Effective Palliation of Symptoms

Conditions
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Bone Metastases

Intervention / Treatment
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* Radiation: Hypofractionated Radiation Treatment
* Radiation: One Radiation Treatment
* Behavioral: Questionnaire


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with a pathologic diagnosis of malignancy Patients with any radiographic evidence of bone metastases, including plain x-ray, bone scan, computed tomography (CT) scan, magnetic resonance imaging (MRI), or positron emission tomography (PET) scan Patients with pain or dysaesthesia Patients with a life expectancy of more than 3 months Patients able to complete pain assessment and quality of life surveys Patients with multiple osseous sites are eligible; however should not treat more than 3 separate radiation treatment fields concurrently. Patients with surgery for osseous metastases are allowed. Exclusion Criteria: Patients with prior radiation therapy to the treatment site Patients with a current, untreated spinal cord compression Patients with a radiographic or pathologic fracture to the treatment site Patients with painful metastases to hands and feet that need to be radiated on protocol Patients previously treated with radioactive isotope (e.g. Sr89) within 30 days of randomization

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hypofractionated Radiation Therapy<br>Participants receive standard hypofractionated regimen of 3 Gy x 10 fractions, 1 radiation treatment a day for 5 days in a row. Questionnaire completion at months 1, 2, 3, 4, and 6 and then every 3 months after that for at least 3 years. Questionnaires ask about pain, pain relief, and quality of life. | Radiation: Hypofractionated Radiation Treatment<br>* Participants receive standard hypofractionated regimen of 3 Gy x 10 fractions, 1 radiation treatment a day for 5 days in a row.<br>* Other names: XRT;Behavioral: Questionnaire<br>* Questionnaire completion at months 1, 2, 3, 4, and 6 and then every 3 months after that for at least 3 years. Questionnaires ask about pain, pain relief, and quality of life.<br>* Other names: Survey;|
| Active Comparator: One Radiation Therapy Treatment<br>12 Gy x 1 fraction or 16 Gy x 1 fractions adaptively depending on the size of the metastases or gross tumor volume (GTV). Questionnaire completion at months 1, 2, 3, 4, and 6 and then every 3 months after that for at least 3 years. Questionnaires ask about pain, pain relief, and quality of life. | Radiation: One Radiation Treatment<br>* 12 Gy x 1 fraction or 16 Gy x 1 fractions adaptively depending on the size of the metastases or gross tumor volume (GTV).<br>* Other names: XRT;Behavioral: Questionnaire<br>* Questionnaire completion at months 1, 2, 3, 4, and 6 and then every 3 months after that for at least 3 years. Questionnaires ask about pain, pain relief, and quality of life.<br>* Other names: Survey;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Intent- to- Treat Patients With Pain Response by Treatment | Evaluate single fraction stereotactic regimen for pain response in terms of time to failure. Pain response was defined by international consensus criteria as a combination of pain score and analgesic use (daily morphine-equivalent dose). Pain failure (ie, lack of response) was defined as worsening pain score (2 points on a 0-to-10 scale), an increase in morphine-equivalent opioid dose of 50% or more, reirradiation, or pathologic fracture. Time to failure was defined as the first occurrence of any of the following events: worsening in pain score by at least 2 categories by MDASI survey. Statistical tests in treatment group were based on the Wilcoxon rank sum test to compare changes in pain scores and analgesic use at each assessment point relative to baseline. Increases or decreases of 2 or more points on a scale of 0 to 10 indicated improving or worsening pain. Fisher exact tests were used to compare the distribution of pain responders (CR + PR) and nonresponders (PP + IR). | From date of registration until the date of first documented Pain failure or death from any cause, or lost to follow up, whichever came first, assessed up to 9 months | 
| Number of Evaluable Participants With Pain Response by Treatment | Evaluate single fraction stereotactic regimen for pain response in terms of time to failure. Pain response was defined by international consensus criteria as a combination of pain score and analgesic use (daily morphine-equivalent dose). Pain failure (ie, lack of response) was defined as worsening pain score (2 points on a 0-to-10 scale), an increase in morphine-equivalent opioid dose of 50% or more, reirradiation, or pathologic fracture. Time to failure was defined as the first occurrence of any of the following events: worsening in pain score by at least 2 categories by MDASI survey. Complete response (CR) is a pain score of 0 at the treated site and no increase in analgesic. Partial response (PR): reduction in pain score of 2 or more points above baseline with no increase in analgesic. Pain progression (PP): Increases of 2 or more points on a scale of 0 to 10 or worsening pain. indeterminate response (IR): were all other responses. | From date of registration until the date of first documented Pain failure or death from any cause, or lost to follow up, whichever came first, assessed up to 9 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Toxicity Associated With Treatment | Report grade 3 acute (skin, fatigue, flare reaction) and long term (sclerosis, bone ossification, bone fracture rate) toxicity associated with treatment. During radiotherapy, the patient will be examined weekly and acute reactions recorded and toxicity occurring after 3 months of radiation therapy. | From date of registration until the date of documented death from any cause, or lost to follow up, whichever came first, assessed up to 2 years. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bone metastases, Hypofractionated Radiation Therapy, Standard Radiation Therapy, XRT, Pain control, Palliation of symptoms, Questionnaire, Survey