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

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.

Study Overview

• Status: Completed
• Conditions: Bone Metastases
• Intervention / Treatment: Radiation: Hypofractionated Radiation Treatment; Behavioral: Questionnaire; Radiation: One Radiation Treatment

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 167
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Banner MD Anderson Cancer Center
  • New Jersey
    • Voorhees, New Jersey, United States, 08043
      • MD Anderson Cancer Center at Cooper
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients with a pathologic diagnosis of malignancy
2. 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
3. Patients with pain or dysaesthesia
4. Patients with a life expectancy of more than 3 months
5. Patients able to complete pain assessment and quality of life surveys
6. Patients with multiple osseous sites are eligible; however should not treat more than 3 separate radiation treatment fields concurrently.
7. Patients with surgery for osseous metastases are allowed.

Exclusion Criteria:

1. Patients with prior radiation therapy to the treatment site
2. Patients with a current, untreated spinal cord compression
3. Patients with a radiographic or pathologic fracture to the treatment site
4. Patients with painful metastases to hands and feet that need to be radiated on protocol
5. Patients previously treated with radioactive isotope (e.g. Sr89) within 30 days of randomization

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hypofractionated Radiation Therapy; 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; Participants receive standard hypofractionated regimen of 3 Gy x 10 fractions, 1 radiation treatment a day for 5 days in a row.; Other Names: XRT; Behavioral: Questionnaire; 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.; Other Names: Survey
Active Comparator: One Radiation Therapy Treatment; 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.	Behavioral: Questionnaire; 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.; Other Names: Survey; Radiation: One Radiation Treatment; 12 Gy x 1 fraction or 16 Gy x 1 fractions adaptively depending on the size of the metastases or gross tumor volume (GTV).; Other Names: XRT

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: M.D. Anderson Cancer Center
• Investigators: Principal Investigator: Quynh-nhu Nguyen, MD, M.D. Anderson Cancer Center

Publications and helpful links

General Publications

• Nguyen QN, Chun SG, Chow E, Komaki R, Liao Z, Zacharia R, Szeto BK, Welsh JW, Hahn SM, Fuller CD, Moon BS, Bird JE, Satcher R, Lin PP, Jeter M, O'Reilly MS, Lewis VO. Single-Fraction Stereotactic vs Conventional Multifraction Radiotherapy for Pain Relief in Patients With Predominantly Nonspine Bone Metastases: A Randomized Phase 2 Trial. JAMA Oncol. 2019 Jun 1;5(6):872-878. doi: 10.1001/jamaoncol.2019.0192. Erratum In: JAMA Oncol. 2021 Oct 1;7(10):1581.

Helpful Links

• University of Texas MD Anderson Cancer Center Website

Study record dates

Study Major Dates

• Study Start (Actual): August 6, 2014
• Primary Completion (Actual): September 2, 2020
• Study Completion (Actual): September 2, 2020

Study Registration Dates

• First Submitted: June 9, 2014
• First Submitted That Met QC Criteria: June 11, 2014
• First Posted (Estimate): June 13, 2014

Study Record Updates

• Last Update Posted (Actual): November 8, 2021
• Last Update Submitted That Met QC Criteria: October 11, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Questionnaire; Survey; Bone metastases; XRT; Pain control; Hypofractionated Radiation Therapy; Standard Radiation Therapy; Palliation of symptoms
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplasms by Site; Hematologic Diseases; Musculoskeletal Diseases; Neoplastic Processes; Bone Diseases; Neoplasm Metastasis; Bone Neoplasms; Bone Marrow Diseases
• Other Study ID Numbers: 2013-0640; NCI-2014-01482 (Registry Identifier: NCI CTRP)