Prophylactic Radiotherapy for Spinal Metastases

(PROMISSeD Trial)

Overseen By Antoinette Pimental

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Baptist Health South Florida

Disqualifiers: Previous RT, Serious comorbidities, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: Up to 1 year

74 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether early radiation therapy (prophylactic radiotherapy) can prevent serious bone issues in people with certain cancers that have spread to the spine but cause minimal pain. The goal is to determine if early treatment of these spots can prevent problems like hospital visits later. The trial compares two groups: one receiving early radiation and the other following standard cancer treatments. Suitable candidates have cancer spread to five or more locations, with certain high-risk spine areas affected, and do not require strong pain medication. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this potentially beneficial therapy.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that preventive radiotherapy, a type of radiation treatment given to stop problems before they start, is generally well-tolerated in patients with cancer that has spread to the bones. Studies have found that radiotherapy for bone metastases can help manage pain and improve quality of life.

While detailed safety information for patients without symptoms is limited, early studies suggest it is safe for those with minimal symptoms. The treatment aims to prevent serious bone issues like fractures. Side effects are usually mild and temporary, such as skin irritation or fatigue.

As this trial is in its early stages, it focuses on understanding the safety and effectiveness of the treatment. Therefore, specific data on side effects for this use is limited. However, radiotherapy in other cases of bone metastases has generally been safe.

Prospective participants should discuss any concerns or questions with their doctor before joining the trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about prophylactic radiotherapy for spinal metastases because it takes a proactive approach by targeting high-risk bone areas before symptoms develop, potentially preventing complications. Unlike the standard of care, which usually involves systemic therapy and addresses symptoms as they arise, this method focuses on the highest-risk bone metastases right from the start, aiming to stop problems before they occur. This preemptive strategy could lead to better outcomes by reducing the likelihood of painful skeletal events and maintaining patients' quality of life.

What evidence suggests that prophylactic radiotherapy might be an effective treatment for spinal metastases?

Research has shown that starting radiation therapy (RT) early can benefit patients with cancer that has spread to other parts of the body. In this trial, participants in the Prophylactic Radiation Therapy arm will receive upfront prophylactic radiotherapy to high-risk bone metastases, even if they aren't causing symptoms yet. This approach can lower the chances of bone problems like fractures and reduce hospital visits. One study discovered that a single dose of radiation effectively addresses issues like spinal cord pressure caused by cancer spread. Early RT use is also linked to better quality of life and health outcomes for cancer patients. Overall, these findings suggest that early radiation can help manage cancer spread to the spine before it causes issues. ^{1 2 6 7 8}

Who Is on the Research Team?

Rupesh R Kotecha, MD

Principal Investigator

Miami Cancer Institute

Are You a Good Fit for This Trial?

This trial is for adults with solid tumor malignancy and multiple spinal metastases that are minimally symptomatic. They should have a good performance status, not be pregnant or breastfeeding, and agree to use contraception. It's not for those who've had prior radiation at the treatment site, have serious health issues preventing RT, or where joining would delay their care.

Inclusion Criteria

My cancer has spread to more than 5 different areas.

Exclusion Criteria

Patients whose entry to the trial will cause unacceptable clinical delays in their planned management

I've had radiation therapy before where we now want to treat, and can't have more without risking harm to healthy tissues.

My cancer has spread to my bones, risking spinal damage or bone breakage.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive upfront prophylactic radiotherapy to ≤ 5 highest risk bone metastases followed by standard of care

Up to 1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of skeletal-related events and quality of life

12 months

Assessments at 3, 6, and 12 months

What Are the Treatments Tested in This Trial?

Interventions

• Prophylactic Radiotherapy

Trial Overview

The study tests if early radiotherapy (RT) on asymptomatic or slightly symptomatic spinal metastases can prevent skeletal-related events better than standard systemic therapy alone. The goal is to see if this upfront RT reduces hospitalizations and complications from these bone lesions.

How Is the Trial Designed?

Group I: Prophylactic Radiation Therapy Experimental Treatment 1 Intervention

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%

Group II: Standard of Care Systemic Therapy or Surveillance Active Control 1 Intervention

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)

Prophylactic Radiotherapy is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Prophylactic Radiotherapy for:

• Prevention of skeletal-related events in minimally symptomatic spinal metastases

Approved in United States as Prophylactic Radiotherapy for:

• Palliative treatment of minimally symptomatic spinal metastases to prevent skeletal-related events

Approved in Canada as Prophylactic Radiotherapy for:

• Early intervention for asymptomatic or minimally symptomatic spinal metastases to reduce the risk of skeletal-related events

Who Is Running the Clinical Trial?

Baptist Health South Florida

Lead Sponsor

Trials

54

Recruited

8,100+

Published Research Related to This Trial

In a study of 220 patients who received re-irradiation for metastatic spinal cord compression, the incidence of serious adverse events like radiation-induced myelopathy (RIM) and radiation-induced vertebral fracture (RIF) was low, with only 6 and 9 cases respectively.

Diabetes was identified as a significant risk factor for increased toxicity from re-irradiation, suggesting that careful consideration of a patient's diabetes status is important before proceeding with spinal re-irradiation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diabetes increases the risk of serious adverse events after re-irradiation of the spine. Suppli, MH., Munck Af Rosenschöld, P., Pappot, H., et al.[2020]

External beam radiotherapy effectively manages pain from bone metastases, including cases of spinal canal compression and pathological fractures, potentially preventing further complications.

Single-dose radiotherapy is a highly cost-effective palliative treatment option for patients with bone metastases, making it a practical choice for pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of external beam radiotherapy in the management of bone metastases. Agarawal, JP., Swangsilpa, T., van der Linden, Y., et al.[2022]

In a study of 95 patients with spinal metastases, local radiotherapy achieved an overall pain relief response rate of 82.2%, with 38.3% experiencing complete relief and 43.8% partial relief, regardless of the treatment method used.

Both hypofractionated and single fraction radiotherapy were found to be as effective as longer treatment courses, providing significant benefits in pain management and fracture prevention for patients with spinal metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation therapy of spinal metastases: results with different fractionations. Tombolini, V., Zurlo, A., Montagna, A., et al.[2022]

In a study of 342 patients with painful spinal metastases, 73% responded positively to radiotherapy, which is shown to be a safe and effective noninvasive treatment for pain management.

The median overall survival for these patients was 7 months, with a new scoring system developed to predict survival based on factors like performance status and the presence of visceral metastases, helping guide treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prediction of survival in patients with metastases in the spinal column: results based on a randomized trial of radiotherapy. van der Linden, YM., Dijkstra, SP., Vonk, EJ., et al.[2022]

Radiotherapy is highly effective for alleviating pain in patients with skeletal metastases, achieving pain relief in nearly all cases with minimal side effects, based on a review of 171 studies involving over 13,000 patients.

Half-body irradiation is particularly effective for treating multiple metastatic sites, although its implementation requires more resources and infrastructure, highlighting the need for careful consideration in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Skeletal metastases. Möller, T.[2019]

Radiation therapy is a crucial treatment for cancer patients, with 30% to 50% of treatments aimed at palliative care to relieve symptoms and maintain quality of life.

It is generally effective at targeting localized cancer and has minimal systemic side effects, making it a safe option for managing cancer-related symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palliative radiotherapy--new approaches. van Oorschot, B., Rades, D., Schulze, W., et al.[2022]

Dose-escalated radiotherapy (RT) for spinal metastases and paraspinal tumors showed an impressive local control rate of 88% after 2 years, with only one local recurrence observed among 14 patients treated.

The treatment was safe, with only mild to moderate acute skin toxicity in 2 patients and no cases of radiation-induced myelopathy, indicating that this approach can effectively manage pain and control tumor growth without significant long-term side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical outcome of dose-escalated image-guided radiotherapy for spinal metastases. Guckenberger, M., Goebel, J., Wilbert, J., et al.[2022]

Palliative radiotherapy is an effective treatment for bone metastases in breast cancer patients, primarily aimed at relieving pain, stabilizing bone structure, and preventing complications like spinal cord compression.

The treatment requires careful consideration of individual patient factors, such as life expectancy and tumor progression, and may have side effects like nausea and myelotoxicity, necessitating monitoring and supportive care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiotherapy of Bone Metastasis in Breast Cancer Patients - Current Approaches. Feyer, PC., Steingraeber, M.[2022]

Palliative radiotherapy is a safe and effective method for relieving various symptoms in cancer patients, offering a time-efficient and cost-effective treatment option.

To optimize palliative care, there is a need for better survival prognostication and comprehensive treatment guidelines that utilize both existing and new radiotherapy technologies, especially as the number of cancer patients continues to rise.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palliative radiotherapy: past, present and future-where do we go from here? Lutz, S., Chow, E.[2019]

Palliative radiotherapy is an effective treatment for painful bone metastases, commonly seen in advanced cancer patients, with a response rate of 60-80% in alleviating pain and improving quality of life.

This treatment is typically administered in a collaborative approach involving various specialists, ensuring rapid symptom control with minimal side effects for patients suffering from conditions like prostate, breast, and lung cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Palliative Radiotherapy - An Important Tool in the Event Of Painful Bone Metastases]. Guninski, RS., Blum, D., Guckenberger, M.[2021]

Patients with spinal metastases often felt inadequately informed about the expected outcomes of their treatment, despite being well-informed about procedures and complications.

Most patients' expectations for pain relief and improved daily functioning were only partially met after treatment, highlighting the need for better communication between patients and healthcare providers to set realistic treatment expectations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient Expectations About Palliative Treatment for Symptomatic Spinal Metastases: A Qualitative Study. Gal, R., Charest-Morin, R., Verlaan, JJ., et al.[2023]

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Palliative Radiation Therapy For Bone Metastases - NCBI - NIH

8Gy single-dose radiotherapy is effective in metastatic spinal cord compression: results of a phase III randomized multicentre Italian trial.

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A Multicenter, Randomized Phase II Clinical Trial - PubMed

Radiation delivered prophylactically to asymptomatic, high-risk bone metastases reduced SRE and hospitalizations.

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A New Standard of Care or Need for More Data?

Single fraction radiotherapy is efficacious: A further analysis of the Dutch Bone Metastasis Study controlling for the influence of retreatment.

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