Radiation Therapy for Bone Cancer

(1-2 PUNCH Trial)

Overseen By UCCC Clinical Trials Office

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: University of Cincinnati

Must not be taking: Investigational agents

Disqualifiers: Widespread metastases, Complicated bone metastases, Liquid malignancies, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores two different radiation treatments to ease pain and improve quality of life for individuals with bone cancer that has spread. One group receives a standard dose of radiation (Conventional Radiation Dose), while the other receives a higher dose over two sessions (Experimental Radiation Dose). The trial targets those with 1-3 new or newly painful bone spots linked to cancer, causing noticeable pain. Participants should have a solid cancer history, with pain directly tied to these bone lesions, and must not have recently undergone chemotherapy. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot have chemotherapy within 2 weeks before starting the study, but you can continue hormonal or endocrine therapies during the trial.

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

Research has shown that standard radiation therapy, such as the 8 Gy given in one session used in the trial, is generally safe for treating cancer that has spread to the bones. Studies have found that this method effectively reduces pain and has a well-established safety record. Most patients tolerate this treatment well, though some might experience side effects like skin irritation or tiredness.

For the experimental 16 Gy given in two sessions, studies of similar treatments with higher doses in fewer sessions suggest it is also safe. Patients receiving these higher doses have experienced low rates of serious side effects. The risk of harming nearby organs, like the spinal cord, remains low because the treatment is precisely targeted.

Both treatments aim to manage symptoms with minimal impact on quality of life. While side effects can occur, they are usually mild and manageable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the experimental radiation dose for bone cancer because it offers a potentially more effective approach than the conventional treatment. Most bone cancer treatments use a standard radiation dose of 8 Gy in a single fraction, but this trial explores a higher dose of 16 Gy divided into two fractions. This method could enhance the treatment's effectiveness by delivering more targeted radiation over a slightly extended period, possibly leading to better cancer control with similar or manageable side effects. If successful, this experimental dose could improve patient outcomes and offer a new standard for treating bone cancer.

What evidence suggests that this trial's treatments could be effective for metastatic bone disease?

Research has shown that radiation therapy can relieve pain from cancer that has spread to the bones. In this trial, participants will receive either a conventional radiation dose or an experimental one. One study found that a single dose of 8 Gy radiation, which participants in the conventional dose arm will receive, effectively relieves pain. However, some early studies suggest that a higher dose, like 16 Gy split into two sessions, as in the experimental arm, might further improve pain relief and quality of life. Higher doses can attack cancer cells more aggressively. While the exact benefits of the higher dose are still under investigation, there is hope it could provide even greater relief for patients. ^{2 6 7 8 9}

Who Is on the Research Team?

Timothy Struve, MD

Principal Investigator

University of Cincinnati

Are You a Good Fit for This Trial?

Adults with solid cancer and 1-3 new or newly painful bone metastases, confirmed by scans. They should have pain linked to these lesions, be able to perform daily activities (ECOG ≤3 or Karnofsky ≥40%), and not have widespread metastatic disease that would affect the trial's results. Pregnant women, those with liquid malignancies like lymphoma, uncontrolled illnesses, or recent chemotherapy are excluded.

Inclusion Criteria

I experience pain from new cancer spread to my bones.

Ability to understand and sign written informed consent

My cancer diagnosis was confirmed through tissue or cell testing.

Exclusion Criteria

I haven't had chemotherapy in the last 2 weeks.

Receiving other investigational agents

My cancer has spread widely, making it hard to tell where my bone pain comes from.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation Treatment

Participants receive either conventional (8 Gy in a single fraction) or experimental (16 Gy in 2 fractions) palliative radiation therapy

1-2 weeks

2-3 visits (in-person)

Follow-up

Participants are monitored for pain response and safety, with assessments at 1 month post radiation completion

1 month

1 visit (in-person)

Extended Follow-up

Participants' pain response, quality of life, and overall survival are assessed at 2, 3, 6 months, and up to 2 years post-treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Conventional Radiation Dose
• Experimental Radiation Dose

Trial Overview

The study compares two radiation therapy doses for bone metastasis pain relief: a conventional single dose of 8 Gy versus an experimental split dose of 16 Gy in total. Participants will be randomly assigned to one of these treatments in equal numbers and monitored for pain reduction and quality of life improvements.

How Is the Trial Designed?

Group I: Experimental Radiation Dose Experimental Treatment 1 Intervention

16 Gy in 2 fractions

Group II: Conventional Radiation Dose Active Control 1 Intervention

8 Gy in a single fraction

Conventional Radiation Dose is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as External Beam Radiation Therapy for:

• Painful bone metastases
• Symptomatic bone metastases

Approved in United States as Palliative Radiation Therapy for:

• Metastatic bone disease
• Painful bone metastases
• Symptomatic bone metastases

Approved in Canada as External Beam Radiation Therapy for:

• Painful bone metastases
• Symptomatic bone metastases

Approved in Japan as Palliative Radiation Therapy for:

• Metastatic bone disease
• Painful bone metastases
• Symptomatic bone metastases

Who Is Running the Clinical Trial?

University of Cincinnati

Lead Sponsor

Trials

442

Recruited

639,000+

Published Research Related to This Trial

Approximately 70% of patients with bone metastases experience pain relief from palliative external beam radiotherapy, with some noticing improvement within 48 to 72 hours, although others may take up to 4 weeks for significant relief.

Treatment plans should be personalized based on individual patient factors, and external beam radiotherapy is particularly beneficial after surgeries for fractures to enhance recovery and reduce the need for additional surgeries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

General principles of external beam radiation therapy for skeletal metastases. Frassica, DA.[2018]

A study of 176 deceased men with metastatic prostate cancer revealed that those treated with external beam radiation therapy (EBRT) for bone pain had an average treatment cost of $7,084 per episode, with significant costs attributed to hospital charges (70%).

About 50.6% of the patients received multiple EBRT episodes, indicating that ongoing treatment may be necessary for managing bone metastases, which should be considered in palliative care planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost of palliative external beam radiotherapy (EBRT) use for bone metastases secondary to prostate cancer. Nickman, NA., Ye, X., Gaffney, DK., et al.[2015]

In a study involving 89 patients undergoing external beam radiation therapy (EBRT) for bone metastases, daily pain score assessments by radiation therapists led to a significant reduction in pain, with scores decreasing to 37.5%, 50%, and 75% of pretreatment levels by Days 2, 4, and 10, respectively.

The majority of patients (91%) experienced improved pain levels by the end of treatment, and 83% maintained these improvements at a one-month follow-up, highlighting the effectiveness of daily monitoring in managing pain during radiation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A simple and effective daily pain management method for patients receiving radiation therapy for painful bone metastases. Andrade, RS., Proctor, JW., Slack, R., et al.[2021]

In a study of 17,859 patients with bone metastases, the use of single-fraction radiation therapy increased from 3% in 2010 to 7% in 2015, indicating a gradual shift towards more efficient treatment options.

Despite the increase in single-fraction treatments, the most common regimen remained 30 Gy in 10 fractions, suggesting that while trends are changing, traditional methods are still prevalent in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trends in Radiation Fractionation for Bone Metastases: A Contemporary Nationwide Analysis. Wegner, RE., Matani, H., Colonias, A., et al.[2021]

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]

The implementation of a dedicated palliative radiation oncology service significantly increased the use of single fraction radiation therapy (SF-RT) from 6.4% to 22.3% and hypofractionated radiation (hypo-RT) from 27.6% to 53.5% among patients with bone metastases, indicating improved access to effective pain management options.

Patients treated at the palliative service were 3.3 times more likely to receive SF-RT and 2.5 times more likely to receive hypo-RT, demonstrating that specialized services can enhance the delivery of effective radiation treatments for managing bone metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of a dedicated palliative radiation oncology service on the use of single fraction and hypofractionated radiation therapy among patients with bone metastases. Skamene, S., Agarwal, I., Makar, M., et al.[2018]

Hypofractionated radiotherapy (Group B) provided faster pain relief for patients with bone metastases from hepatocellular carcinoma (HCC), requiring fewer treatment sessions compared to conventional fraction radiotherapy (Group A).

Both treatment methods showed similar overall survival rates and minimal toxicity, indicating that hypofractionated radiotherapy is a safe and effective option for patients, especially those with shorter predicted survival times.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized trial of conventional fraction versus hypofraction radiotherapy for bone metastases from hepatocellular carcinoma. He, J., Shi, S., Ye, L., et al.[2020]

From 2015 to 2017, short-course external-beam radiation therapy (EBRT) for bone metastases increased, while long-course EBRT decreased by 8%, indicating a shift towards more efficient treatment options.

Stereotactic body radiation therapy (SBRT) usage rose to 7% of treatments, showing a growing acceptance of complex techniques, although expenditures for these advanced modalities decreased, suggesting improved cost-effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trends in Radiation Therapy for Bone Metastases, 2015 to 2017: Choosing Wisely in the Era of Complex Radiation. Santos, PMG., Lapen, K., Zhang, Z., et al.[2022]

Stereotactic body radiation therapy (SBRT) provides better pain relief compared to external beam radiation therapy (EBRT) for patients with painful vertebral bone metastases, but it is more expensive, resulting in a cost-effectiveness ratio of $124,552 per quality-adjusted life year (QALY) gained.

SBRT may become cost-effective if patients have a median survival of 11 months or more, suggesting that it could be a better option for patients expected to live longer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness analysis of single fraction of stereotactic body radiation therapy compared with single fraction of external beam radiation therapy for palliation of vertebral bone metastases. Kim, H., Rajagopalan, MS., Beriwal, S., et al.[2022]

Patients with asymptomatic bone metastases who received external beam radiation therapy (EBRT) experienced a significant delay in the onset of moderate-to-severe pain and skeletal-related events (SREs), with a median time of 81 months compared to 25 months for untreated patients (P<0.001).

EBRT was particularly effective in delaying pain and SREs in prostate and lung cancer patients, although it did not show the same benefit for breast cancer patients, and it did not affect overall survival rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

External beam radiation therapy (EBRT) for asymptomatic bone metastases in patients with solid tumors reduces the risk of skeletal-related events (SREs). Shulman, RM., Meyer, JE., Li, T., et al.[2020]

Current best practice for palliative radiotherapy for uncomplicated bone metastases from lung cancer recommends a single dose of 8Gy, but only about 39.6% of surveyed practitioners would use this schedule for painful spinal lesions.

There is a significant gap between evidence-based recommendations and actual clinical practice, with varying preferences for treatment schedules among practitioners, particularly for complicated cases like impending fractures or spinal cord compression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palliative radiotherapy for bone metastases from lung cancer: Evidence-based medicine? Fairchild, A.[2020]

External beam radiation therapy (EBRT) is an effective treatment for managing pain and preventing complications from bone metastases, with various fractionation schemes providing equivalent pain relief as shown in numerous clinical trials.

The treatment is generally well tolerated with established toxicity profiles, and ongoing clinical trials are exploring the roles of adjunct therapies like radiopharmaceuticals and high-dose stereotactic radiation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

External beam radiotherapy and bone metastases. Johnstone, C., Lutz, ST.[2022]

The American Society for Radiation Oncology has released updated, evidence-based guidelines for using external-beam radiotherapy (EBRT) to treat painful bone metastases, emphasizing the importance of these guidelines in improving patient care and quality indices at radiotherapy centers.

Recent findings highlight the need for proper management of pain flare reactions that can occur after starting radiotherapy, as well as the validation of the EORTC QLQ-BM22 quality-of-life module for assessing patient well-being in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent important developments in the management of nonspine bone metastases. Zeng, L., Lutz, S., Chow, E., et al.[2012]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8917266/

Clinical Outcomes of Dose-Escalated Hypofractionated ...

The objective of this study was to determine the toxicities and outcomes of patients with spinal metastasis treated with external beam radiation therapy ...

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05115331

Study Details | NCT05115331 | Palliative UNConventional ...

This is a randomized Phase III study evaluating the efficacy of hypofractionated and dose-escalated palliative radiation therapy in metastatic bone disease (MBD) ...

3.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S1053429622000765

Radiation Therapy for Painful Bone Metastases

EBRT is a well-established, safe modality for effective palliation of pain from bone metastases. A single fraction of 8 Gy provides the same pain relief.

4.

practicalradonc.org

practicalradonc.org/article/S1879-8500(24)00099-7/fulltext

External Beam Radiation Therapy for Palliation of ...

Multiple RCTs evaluated the most effective single-fraction dose of palliative RT. The consensus of these studies determined that 800 cGy in 1 ...

5.

asco.org

asco.org/abstracts-presentations/ABSTRACT154653

A cross-sectional view of radiation fractionation schemes ...

The cost implications of palliative radiation therapy dose and fractionation for painful metastatic bone lesions. First Author: Mark Raymond Waddle.

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12512287/

Study protocol: feasibility and safety of conventional ...

Conventional external beam radiotherapy (EBRT) provides effective symptom relief, but local progression remains frequent. Stereotactic body ...

7.

thegreenjournal.com

thegreenjournal.com/article/S0167-8140(22)04147-0/fulltext

ESTRO ACROP guidelines for external beam ...

General consensus is that an estimated survival of 6–12 weeks would be the minimum life expectancy required for relatively simple procedures to ...

8.

sciencedirect.com

sciencedirect.com/science/article/pii/S0167814012005415

Single fraction conventional external beam radiation ...

To determine the optimal dose of single fraction conventional palliative radiation therapy for the relief of pain caused by bone metastases.

9.

ncbi.nlm.nih.gov

ncbi.nlm.nih.gov/books/NBK603757/

Palliative Radiation Therapy For Bone Metastases - NCBI - NIH

Patients should be followed after palliative radiotherapy treatments to monitor for adverse effects and to evaluate treatment effectiveness.