Prophylactic Radiotherapy of MInimally Symptomatic Spinal Disease (PROMISSeD)

December 26, 2023 updated by: Baptist Health South Florida

Prophylactic Radiotherapy of MInimally Symptomatic Spinal Disease (PROMISSeD Trial)

Early palliative care has been shown to improve the quality of life and even survival for patients with metastatic cancer. More and more supportive oncology teams in cancer centers now advocate for early integration of radiation therapy (RT) in a patient's palliative management course. While multiple randomized studies have evaluated the efficacy of different RT regimens in the treatment of symptomatic bone lesions, few studies have examined the impact of early, upfront RT for asymptomatic or minimally symptomatic (non- opioid dependent) spine metastases and its efficacy in preventing skeletal-related events (SREs). Since the pathophysiology of spinal metastatic disease is distinct from other bony metastatic disease, the proposed trial seeks to understand whether it is beneficial to patients with minimally symptomatic disease to undergo upfront RT to reduce the risks of SREs and their sequelae, including hospitalizations.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

74

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Histologically-confirmed solid tumor malignancy with greater than 5 sites of metastatic disease detected on cross-sectional imaging.

  2. Has high-risk bone metastases that are asymptomatic or minimally symptomatic (not requiring opioids). High risk metastases are defined as:

    1. Bulkiest sites of spinal osseous disease ≥ 2cm,
    2. Disease at junctional levels, including the thoracic apex (Occiput to C2, C7-T1, T12-L2, and L5- S1)
    3. Disease with posterior element involvement, including interspinous, unilateral, or bilateral facet joints.
    4. Vertebral body compression deformity > 50%.
  3. Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2.
  4. Age ≥ 18 years.
  5. Able to provide informed consent.
  6. Patients at reproductive potential must agree to practice an effective contraceptive method. Women of childbearing potential must not be pregnant or lactating.

Exclusion Criteria:

  1. Previous RT to the intended treatment site that precludes developing a treatment plan that respects normal tissue tolerances.
  2. Serious medical co-morbidities precluding RT.
  3. Pregnant or lactating women.
  4. Target lesion(s) is/are complicated bone metastases that include clinical or radiological evidence of spinal cord compression or impending pathological fracture.
  5. Leptomeningeal disease.
  6. Patients whose entry to the trial will cause unacceptable clinical delays in their planned management.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Standard of Care Systemic Therapy or Surveillance
Patients randomized to arm 1 will undergo appropriate systemic therapy as determined by their oncology team. These patients will either continue the current therapy or be transitioned to a new standard of care therapy at the discretion of the treating oncologist. If randomized to arm 1, these patients may also undergo palliative radiation therapy for progressive or painful lesions (a skeletal related event as defined in the study) at the time of symptom development*(not upfront palliative radiation therapy)
Drug: Standard of care systemic therapy
Standard of care systemic therapy, including chemotherapeutics, targeted therapies, immunomodulatory agents, and hormonal therapies will be delivered at the discretion of the treating medical oncologist. Patients may receive systemic therapy concurrently and there are no restrictions on initiation of systemic agents after radiotherapy including immunotherapy and hormonal therapy, the timing of which will be determined by a consensus between the treating medical and radiation oncologists.
Experimental: Prophylactic Radiation Therapy

Patients randomized to Arm 2 of the study will undergo upfront prophylactic radiotherapy to ≤ 5 highest risk bone metastases followed by standard of care, as defined by:

  1. Bulkiest sites of disease ≥ 2cm (can include paraspinal disease extension)
  2. Disease in junctional spine (Occ-C2, C7-T1, T12-L1, L5-S1)
  3. Disease with posterior element involvement (facet(s), interspinous)
  4. Compression Deformity > 50%
Radiation: Prophylactic Radiotherapy
Radiation therapy will be delivered according to department standards. For this protocol, total dose and dose fractionation may be delivered at the discretion of the treating radiation oncologist according to department standards. All techniques including conventional, three-dimensional conformal radiation therapy (3D-CRT), intensity-modulated radiation therapy (IMRT), and stereotactic radiosurgery/stereotactic body radiation therapy (SRS/SBRT) techniques may be used. Image guidance at the time of treatment delivery to verify patient positioning may be chosen at the discretion of the treating radiation oncologist according to department standards.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of patients who have skeletal-related events (SREs)
Time Frame: 1 year
Number of skeletal related events (SREs), which will be defined as pathological fractures, spinal cord compression, or interventions (palliative RT, interventional procedures, or spine surgery)
1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of skeletal-related event (SRE) hospitalizations
Time Frame: 1 year
Number of hospitalizations attributed to skeletal-related events (SREs)
1 year
Pain-related quality of life
Time Frame: 3 months, 6 months, and 12 months, optionally within 1 week of a skeletal-related event (SRE)
Pain-related quality of life using the Brief Pain Inventory (BPI) form. The BPI is a 17-item patient self-rating scale assessing demographic data, use of medications, as well as the sensory and reactive components of pain. The scale is from 0-10, and there are breakpoints between scores of 4 and 5 and between 6 and 7, indicating that mild pain correlates with scores of 1-4, moderate pain with 5-6, and severe pain with scores of 7-10.
3 months, 6 months, and 12 months, optionally within 1 week of a skeletal-related event (SRE)
Health care utilities and quality of life
Time Frame: 3 months, 6 months, and 12 months, optionally within 1 week of a skeletal-related event (SRE)
Health care utilities and quality of life using the EuroQol Group EQ-5D-5L form. It has been developed to generate a generic cardinal index of health, thus giving it considerable potential for future use in economic evaluation. The EQ-5D-5L is a two-part, patient-completed questionnaire. The first part consists of 5 items covering 5 dimensions including: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension can be graded on 3 levels including: 1=no problems; 2= moderate problems; and 3=extreme problems. The second component is the visual analog scale, where the participant rates their own overall health on a scale of 0 (worst health) to 100 (best health).
3 months, 6 months, and 12 months, optionally within 1 week of a skeletal-related event (SRE)
Pain-free survival (PFS)
Time Frame: Until 1 year
Pain-free survival (PFS) is defined as the time from study entry to until the start of opioid use or until death.
Until 1 year
Overall survival (OS)
Time Frame: Until 1 year
Overall survival (OS) is defined as the time from study entry until death.
Until 1 year
Adverse event frequency and severity
Time Frame: 3 months, 6 months, and 12 months
Evaluate CTCAE v5 toxicity events in the upfront RT arm by tabulating all toxicities and summarizing the CTCAE v5 scores.
3 months, 6 months, and 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Baptist Health South Florida

Investigators

  • Principal Investigator: Rupesh R Kotecha, MD, Miami Cancer Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 29, 2022

Primary Completion (Estimated)

September 1, 2026

Study Completion (Estimated)

September 1, 2027

Study Registration Dates

First Submitted

September 6, 2022

First Submitted That Met QC Criteria

September 6, 2022

First Posted (Actual)

September 9, 2022

Study Record Updates

Last Update Posted (Estimated)

December 27, 2023

Last Update Submitted That Met QC Criteria

December 26, 2023

Last Verified

December 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2021-KOT-002

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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