Cryoablation + SBRT for Bone Metastasis Pain

Overseen By Rahul A. Sheth, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Antiplatelets, Anticoagulants

Disqualifiers: Pregnancy, Active infection, Cardiac arrhythmia, others

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

Compensation: Varies

Number of Visits: 10

Duration: 1-2 weeks

40 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial compares cryoablation combined with stereotactic body radiation therapy to stereotactic body radiation therapy alone to see how well they work in treating patients with pain from cancer that has spread to the bones (bone metastases). Bone is a common site of metastasis in advanced cancer, and bone metastases often result in debilitating cancer-related pain. The current standard of care to treat painful bone metastases is radiation therapy alone. However, many patients do not get adequate pain relief from radiation therapy alone. Another type of therapy that may be used to provide pain relief from bone metastases is cryoablation. Cryoablation is a procedure in which special needles are inserted into the tumor site. These needles grow ice balls at their tips to freeze and kill cancer cells. The goal of this trial is to compare how well cryoablation in combination with radiation therapy works to radiation therapy alone when given to cancer patients to provide pain relief from bone metastases.

Will I have to stop taking my current medications?

If you are taking antiplatelet or anticoagulation medications, you may need to stop them 48 hours before the procedure, unless the study doctor decides otherwise. Other standard treatments like chemotherapy, immunotherapy, or targeted therapy are allowed.

What data supports the effectiveness of this treatment for bone metastasis pain?

Research shows that stereotactic body radiation therapy (SBRT) can provide better pain relief and local control for bone metastases compared to conventional radiotherapy, with lower retreatment rates and improved pain response, especially in spinal metastases. ^{1 2 3 4 5}

Is the combination of Cryoablation and SBRT safe for treating bone metastasis pain?

Stereotactic Ablative Radiotherapy (SABR), also known as Stereotactic Body Radiation Therapy (SBRT), has been used safely in treating various cancers, including lung and prostate cancer, with some reported serious complications. Strategies to reduce these risks are important, and overall, the treatment has shown acceptable safety levels in clinical settings. ^{6 7 8 9 10}

How is the treatment of Cryoablation + SBRT for bone metastasis pain different from other treatments?

Cryoablation combined with Stereotactic Body Radiation Therapy (SBRT) is unique because it uses a precise, high-dose radiation method to target bone metastases, potentially offering better pain relief and local control compared to conventional radiotherapy. This approach allows for fewer treatment sessions and may be more effective for tumors that are resistant to traditional radiation. ^{1 2 3 4 11}

Research Team

Rahul A Sheth, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for cancer patients with painful bone metastases from specific cancers like renal, urothelial, prostate, sarcoma, thyroid, colorectal carcinoma and melanoma. Participants must have a pain score of at least 4/10 on the BPI scale for the affected bone area and a life expectancy of 3+ months. They should be able to stop antiplatelet or anticoagulation meds before procedures if needed.

Inclusion Criteria

Your blood clotting test (INR) should be less than 1.5 within 6 weeks of screening.

You are expected to live for at least 3 more months.

My cancer can be treated with freezing and targeted radiation, as approved by the study leaders.

Exclusion Criteria

My cancer has spread to my spine or skull.

I am not on any experimental drugs but may be on standard cancer treatments.

I have a confirmed fracture at the cancer site that cannot be stabilized with a minimally invasive procedure.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients undergo stereotactic body radiation therapy for 1 fraction or cryoablation followed by stereotactic body radiation therapy within 10 days

1-2 weeks

1-2 visits (in-person)

Follow-up

Participants are monitored for safety, pain response, and local tumor control

24 weeks

9 visits (in-person) at 1, 2, 3, 4, 8, 12, 16, 20, and 24 weeks

Treatment Details

Interventions

• Cryoablation
• Stereotactic Body Radiation Therapy

Trial Overview The CROME Trial is testing whether combining cryoablation (freezing cancer cells using special needles) with stereotactic body radiation therapy provides better pain relief for bone metastases than radiation alone. Patients will either receive both treatments or just radiation to compare effectiveness.

Participant Groups

Group I: Arm B (cryoablation, SBRT) Experimental Treatment 3 Interventions

Patients undergo cryoablation. Within 10 days after cryoablation, patients undergo stereotactic body radiation therapy for 1 fraction. Alternatively, patients may receive stereotactic body radiation therapy initially, followed by cryoablation."

Group II: Arm A (SBRT) Active Control 2 Interventions

Patients undergo stereotactic body radiation therapy for 1 fraction.

Cryoablation is already approved in United States, European Union for the following indications:

Approved in United States as Cryoablation for:

• Liver cancer
• Kidney cancer
• Bone cancer
• Pain management

Approved in European Union as Cryoablation for:

• Liver cancer
• Kidney cancer
• Bone cancer
• Pain management

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Findings from Research

Stereotactic radiotherapy (SBRT) shows promise in improving pain relief and local control in patients with bone metastases, with higher pain response rates compared to conventional radiotherapy, based on a systematic review of 57 studies involving 3995 patients.

Despite the positive findings, the review highlights significant variability in study designs and treatment protocols, indicating a need for large randomized trials to accurately assess the efficacy and safety of SBRT for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic Review of the Role of Stereotactic Radiotherapy for Bone Metastases. Spencer, KL., van der Velden, JM., Wong, E., et al.[2021]

In a study of 20 patients with spine bone metastases treated with stereotactic radio-therapy (SBRT), 74% experienced complete pain relief at three months, indicating a strong analgesic response.

The treatment was well-tolerated, with no severe toxicity (Grade 3 or higher) reported, suggesting that SBRT is a safe and effective option for pain management in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Stereotactic body radiation therapy (SBRT) for pain management in spine bone metastases]. Jara O, N., Solé P, C., Solé Z, S.[2020]

Stereotactic body radiotherapy (SBRT) offers a promising treatment option for painful bone metastases, delivering high doses of radiation accurately over one to a few sessions, which may improve patient outcomes compared to conventional radiotherapy.

SBRT is particularly beneficial for treating tumors that are usually resistant to radiation, although it is important to consider potential toxicity to surrounding healthy tissues and the patterns of local treatment failures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiotherapy in the management of painful bone metastases. Jhaveri, P., Teh, BS., Bloch, C., et al.[2008]

Stereotactic body radiotherapy (SBRT) using a regimen of 24 Gy in 2 fractions has shown high efficacy for treating spinal metastases, with 1-year local control rates between 83-93.9% and low rates of treatment-related complications, such as plexopathy and radiculopathy under 5%.

This SBRT regimen is not only effective for initial treatment but also feasible for reirradiation of previously treated spine metastases, maintaining local control rates of 72-86%, making it a strong option for patients with challenging cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiotherapy for spine metastases: a review of 24 Gy in 2 daily fractions. Nguyen, EK., Ruschin, M., Zhang, B., et al.[2023]

Stereotactic body radiation therapy (SBRT) significantly reduces the risk of local failure and the need for reirradiation in patients with spinal metastases compared to conventional external beam radiation therapy (cEBRT), with local failure rates at 24 months being 14.8% for SBRT versus 35.6% for cEBRT (P < .001).

While SBRT has a lower reirradiation rate (2.2% at 1 year) compared to cEBRT (15.8% at 1 year), it is associated with a higher incidence of grade 3 vertebral compression fractures, indicating a need for careful monitoring of this adverse effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mature Local Control and Reirradiation Rates Comparing Spine Stereotactic Body Radiation Therapy With Conventional Palliative External Beam Radiation Therapy. Zeng, KL., Myrehaug, S., Soliman, H., et al.[2022]

Stereotactic ablative radiotherapy (SABR) using Cyberknife demonstrated high effectiveness in treating stage I non-small-cell lung cancer, with 2-year local control, progression-free, and overall survival rates of 91.9%, 61.7%, and 84.8%, respectively, based on a study of 153 patients.

The treatment was generally safe, with only 8.1% of patients experiencing severe toxicities, including one case of grade 5 radiation pneumonitis, indicating that while SABR is effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic Ablative Radiotherapy Using CyberKnife for Stage I Non-small-cell Lung Cancer: A Retrospective Analysis. Hayashi, K., Suzuki, O., Shiomi, H., et al.[2022]

Stereotactic ablative radiotherapy (SABR) has rapidly expanded in clinical use for treating various primary and metastatic tumors, demonstrating promising results in tumor control.

Despite its effectiveness, SABR can lead to serious complications, highlighting the need for strategies to reduce these risks and improve the safety of the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serious complications associated with stereotactic ablative radiotherapy and strategies to mitigate the risk. Lo, SS., Sahgal, A., Chang, EL., et al.[2018]

Stereotactic ablative radiotherapy (SABR) is an effective treatment for early-stage non-small cell lung cancer, especially for patients who cannot undergo surgery, showing high local tumor control rates with manageable side effects.

The CyberKnife system is particularly advantageous for SABR in lung tumors due to its ability to accurately target moving tumors during breathing, enhancing treatment precision.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CyberKnife stereotactic ablative radiotherapy for lung tumors. Gibbs, IC., Loo, BW.[2022]

CyberKnife stereotactic ablative radiotherapy (SABR) for treating intermediate- to very-high-risk prostate cancer showed a high 3-year biochemical relapse-free survival rate of 90.2%, indicating its efficacy in managing this condition.

The treatment was well-tolerated, with no patients experiencing severe toxicity (≥ grade 3), and only mild genitourinary and gastrointestinal side effects were reported, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic ablative radiotherapy with CyberKnife in the treatment of locally advanced prostate cancer: preliminary results. Fan, CY., Chao, HL., Huang, WY., et al.[2017]

Stereotactic ablative radiotherapy (SABR) shows high effectiveness for oligometastatic breast cancer, achieving local control rates of 97% at 1 year and 90% at 2 years, based on a meta-analysis of 10 studies involving 467 patients.

SABR is associated with a low toxicity rate, with only 4.1% of patients experiencing grade 2 or 3 side effects, indicating it is a safe treatment option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiotherapy to treat breast cancer oligometastases: A systematic review with meta-analysis. Viani, GA., Gouveia, AG., Louie, AV., et al.[2021]

In a study of 93 patients with prostate cancer receiving stereotactic body radiotherapy (SBRT) for spinal metastases, local control rates were very high, with 99% at 1 year and 95% at 2 years for hormone-sensitive prostate cancer (HSPC), but lower for castrate-resistant prostate cancer (CRPC) at 94% and 78%, respectively.

The overall survival rates were significantly better for patients with HSPC, at 98% and 95% at 1 and 2 years, compared to 79% and 65% for those with CRPC, indicating that hormone sensitivity impacts both local control and survival outcomes after SBRT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spine Stereotactic Body Radiotherapy for Prostate Cancer Metastases and the Impact of Hormone Sensitivity Status on Local Control. Abugharib, A., Zeng, KL., Tseng, CL., et al.[2022]

References

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

Systematic Review of the Role of Stereotactic Radiotherapy for Bone Metastases. [2021]

2. Chile pubmed.ncbi.nlm.nih.gov

[Stereotactic body radiation therapy (SBRT) for pain management in spine bone metastases]. [2020]

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

Stereotactic body radiotherapy in the management of painful bone metastases. [2008]

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

Stereotactic body radiotherapy for spine metastases: a review of 24 Gy in 2 daily fractions. [2023]

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

Mature Local Control and Reirradiation Rates Comparing Spine Stereotactic Body Radiation Therapy With Conventional Palliative External Beam Radiation Therapy. [2022]

6. Greece pubmed.ncbi.nlm.nih.gov

Stereotactic Ablative Radiotherapy Using CyberKnife for Stage I Non-small-cell Lung Cancer: A Retrospective Analysis. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Serious complications associated with stereotactic ablative radiotherapy and strategies to mitigate the risk. [2018]

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

CyberKnife stereotactic ablative radiotherapy for lung tumors. [2022]

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

Stereotactic ablative radiotherapy with CyberKnife in the treatment of locally advanced prostate cancer: preliminary results. [2017]

10. Ireland pubmed.ncbi.nlm.nih.gov

Stereotactic body radiotherapy to treat breast cancer oligometastases: A systematic review with meta-analysis. [2021]

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

Spine Stereotactic Body Radiotherapy for Prostate Cancer Metastases and the Impact of Hormone Sensitivity Status on Local Control. [2022]