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

168 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a randomized Phase III study evaluating the efficacy of hypofractionated and dose-escalated palliative radiation therapy in metastatic bone disease (MBD). Patients will be randomized 1:1 to the conventional (8 Gy in a single fraction) and experimental (16 Gy in 2 fractions) groups with baseline and subsequent assessment of both pain and quality of life metrics.

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.

What data supports the effectiveness of this treatment for bone cancer?

Research shows that radiation therapy, including external beam radiation therapy (EBRT) and hypofractionated radiation therapy (shorter courses of treatment), is effective in managing pain from bone metastases. Studies indicate that shorter courses of radiation can be just as effective as longer ones for pain relief, making them a viable option for palliative care. ^{1 2 3 4 5}

Is radiation therapy for bone cancer generally safe for humans?

Radiation therapy, including external beam radiation therapy (EBRT), is generally well tolerated and has well-established safety profiles for treating bone metastases, with various studies showing it is effective in relieving pain and preventing complications. ^{6 7 8 9 10}

How is the radiation therapy treatment for bone cancer different from other treatments?

This treatment uses external beam radiation therapy (EBRT) to relieve pain and prevent complications from bone cancer, offering flexibility in dosage and schedule, such as single or multiple sessions, which can be tailored to the patient's needs. It is generally well-tolerated and can provide pain relief within days, making it a unique option compared to other therapies. ^{1 9 11 12 13}

Research Team

Timothy Struve, MD

Principal Investigator

University of Cincinnati

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

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

Trends in Radiation Fractionation for Bone Metastases: A Contemporary Nationwide Analysis. [2021]

2. England pubmed.ncbi.nlm.nih.gov

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

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

A simple and effective daily pain management method for patients receiving radiation therapy for painful bone metastases. [2021]

4. China 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. [2018]

5. United States 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. [2022]

6. China 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). [2020]

7. Australia pubmed.ncbi.nlm.nih.gov

A randomized trial of conventional fraction versus hypofraction radiotherapy for bone metastases from hepatocellular carcinoma. [2020]

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

Trends in Radiation Therapy for Bone Metastases, 2015 to 2017: Choosing Wisely in the Era of Complex Radiation. [2022]

9. China pubmed.ncbi.nlm.nih.gov

External beam radiotherapy and bone metastases. [2022]

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

Cost of palliative external beam radiotherapy (EBRT) use for bone metastases secondary to prostate cancer. [2015]

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

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

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

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

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

Recent important developments in the management of nonspine bone metastases. [2012]