Prophylactic Radiotherapy for Spinal Metastases

(PROMISSeD Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Rupesh R Kotecha, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Baptist Health South Florida

Disqualifiers: Previous RT, Serious comorbidities, Pregnancy, others

No Placebo Group

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this 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.

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.

What data supports the effectiveness of the treatment Prophylactic Radiotherapy for Spinal Metastases?

Research shows that radiotherapy for spinal metastases can provide pain relief and improve quality of life, with response rates of up to 60-80% in reducing symptoms like pain and preventing complications such as fractures. ^{1 2 3 4 5}

Is prophylactic radiotherapy for spinal metastases safe for humans?

Radiotherapy, including prophylactic radiotherapy, is generally considered safe for humans, with mostly mild side effects. However, it can cause nausea and affect blood cell counts, so monitoring is important, especially when large areas are treated. ^{6 7 8 9 10}

How is prophylactic radiotherapy different from other treatments for spinal metastases?

Prophylactic radiotherapy is unique because it is used early to prevent complications like pain and fractures in patients with spinal metastases, rather than just treating symptoms after they occur. This approach aims to maintain quality of life by addressing potential issues before they become problematic. ^{1 3 4 5 11}

Research Team

Rupesh R Kotecha, MD

Principal Investigator

Miami Cancer Institute

Eligibility Criteria

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.

Has high-risk bone metastases that are asymptomatic or minimally symptomatic (not requiring opioids). High risk metastases are defined as: Bulkiest sites of spinal osseous disease ≥ 2cm, Disease at junctional levels, including the thoracic apex (Occiput to C2, C7-T1, T12-L2, and L5- S1), Disease with posterior element involvement, including interspinous, unilateral, or bilateral facet joints, Vertebral body compression deformity > 50%, Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2, Age ≥ 18 years, Able to provide informed consent, Patients at reproductive potential must agree to practice an effective contraceptive method. Women of childbearing potential must not be pregnant or lactating

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.

Trial Timeline

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

Treatment Details

Interventions

• Prophylactic Radiotherapy (Radiation Therapy)

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.

Participant Groups

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 Canada for the following indications:

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Prediction of survival in patients with metastases in the spinal column: results based on a randomized trial of radiotherapy. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Clinical outcome of dose-escalated image-guided radiotherapy for spinal metastases. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Patient Expectations About Palliative Treatment for Symptomatic Spinal Metastases: A Qualitative Study. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Radiation therapy of spinal metastases: results with different fractionations. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

[Palliative Radiotherapy - An Important Tool in the Event Of Painful Bone Metastases]. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Palliative radiotherapy--new approaches. [2022]

7. Ireland pubmed.ncbi.nlm.nih.gov

Diabetes increases the risk of serious adverse events after re-irradiation of the spine. [2020]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Radiotherapy of Bone Metastasis in Breast Cancer Patients - Current Approaches. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Skeletal metastases. [2019]

10. China pubmed.ncbi.nlm.nih.gov

Palliative radiotherapy: past, present and future-where do we go from here? [2019]

11. England pubmed.ncbi.nlm.nih.gov

The role of external beam radiotherapy in the management of bone metastases. [2022]