Biology-Guided Radiation Therapy for Bone Cancer

Overseen By Yi-Jen Chen, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: City of Hope Medical Center

Disqualifiers: Prior radiation, Spinal cord compression, Fracture, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 1 day

24 Participants Needed

Trial Summary

What is the purpose of this trial?

This clinical trial tests the safety and effectiveness of a single-dose treatment of biology-guided radiation therapy (BgRT) in treating patients with painful cancer that has spread from where it first started (primary site) to the bone (bone metastases). Bone metastases can result in significant pain and reduction in quality of life. Single fraction radiation therapy (SFRT) can produce equivalent pain relief compared to multi-fraction radiation therapy, but SFRT treatments generally lead to higher rates of retreatment. BgRT is a new and innovative form of radiation delivery that uses a signal generated by positron emission tomography to guide external beam radiation therapy. It is a technology breakthrough that uses live, continuously updated data throughout the entire treatment session to determine exactly where to deliver radiotherapy to biologically active tumors. Giving BgRT may be safe and effective in treating patients with painful bone metastases.

Will I have to stop taking my current medications?

The trial requires that participants stop taking systemic therapy (treatments that affect the entire body) for at least one week before and one week after the study intervention.

What data supports the effectiveness of the treatment Biology-Guided Radiation Therapy for Bone Cancer?

Research on similar treatments, like stereotactic body radiotherapy (SBRT), shows it is effective for controlling pain and tumors in bone and spine cancers. SBRT has been shown to improve pain relief and reduce the need for retreatment compared to traditional methods. ^{1 2 3 4 5}

How is Biology-Guided Radiation Therapy different from other treatments for bone cancer?

Biology-Guided Radiation Therapy (BgRT) is unique because it combines PET-CT imaging with a linear accelerator to track and treat tumors in real-time, allowing for precise targeting of cancer cells. This approach uses radiotracers to make tumors visible and enables the radiation to follow the tumor's movements, potentially improving treatment outcomes compared to traditional radiation therapies. ^{6 7 8 9 10}

Research Team

Yi-Jen Chen

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

This trial is for patients with painful cancer that has spread to the bone. Participants must have a life expectancy of at least 3 months, be able to lie still for treatment, and provide written informed consent. Those who are pregnant, breastfeeding, or have certain metal implants near the treatment area cannot join.

Inclusion Criteria

I can take care of myself and perform daily activities.

My cancer has been confirmed through lab tests.

I am currently receiving radiation therapy in up to 3 areas.

Exclusion Criteria

I have untreated spinal cord compression.

Unable to undergo a PET/CT scan

Pregnant and/or breastfeeding women are excluded from this study as these agents may have the potential for teratogenic or abortifacient effects

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo a single fraction of biology-guided radiation therapy (BgRT) on day 0

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including pain response and quality of life assessments

Up to 1 year

Follow-up at 2 weeks, 3 months, and every 3 months thereafter

Treatment Details

Interventions

• Biology-Guided Radiation Therapy

Trial Overview The study tests a single-dose biology-guided radiation therapy (BgRT) using live data from PET scans to target active tumors in bones. It aims to see if BgRT can effectively relieve pain without needing retreatment like standard therapies.

Participant Groups

Group I: Treatment (BgRT) Experimental Treatment 4 Interventions

Patients undergo a single fraction of BgRT on day 0. Patients undergo PET/CT on study and optionally during follow up.

Biology-Guided Radiation Therapy is already approved in United States for the following indications:

Approved in United States as SCINTIX Biology-Guided Radiation Therapy for:

• Bone metastases
• Lung cancer

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a study of 434 patients treated with stereotactic body radiation therapy (SBRT) for bone metastases, a biologically effective dose (BED10) of 50 or higher was linked to better local control of oligometastatic lesions, while larger planning target volumes (PTV) for nonspine lesions predicted worse local control.

Factors such as prostate cancer histology, a performance status of 0 to 1, and a metastasis-free interval of 2 years or more were associated with improved progression-free survival (PFS) and overall survival (OS), highlighting the importance of patient selection in optimizing treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient and Treatment Factors Associated With Improved Local Control and Survival in Oligometastatic Bone Disease: Results From a Large Single-Institution Experience Using Stereotactic Body Radiation Therapy. Thomas, MC., Chen, YH., Fite, E., et al.[2022]

Stereotactic body radiotherapy (SBRT) demonstrated high local control rates of 95% according to WHO criteria and 98% according to RECIST criteria in a study of 59 patients with metastatic spine tumors, indicating its efficacy in managing these cases.

The study found that while WHO criteria are more sensitive to changes in tumor size, RECIST criteria are simpler and reproducible, making them a suitable standard for evaluating treatment response after SBRT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A quantitative and comparative evaluation of stereotactic spine radiosurgery local control: proposing a consistent measurement methodology. Harel, R., Kaisman-Elbaz, T., Emch, T., et al.[2022]

In a Phase I study involving 15 patients with metastatic spinal disease, intensity-modulated, near-simultaneous CT image-guided stereotactic body radiotherapy (SBRT) was found to be a feasible and highly precise treatment method, with no observed neurologic toxicity.

The treatment setup was accurate within 1 mm of the planned isocenter, and the study reported a maximum estimated probability of paralysis of no greater than 18.1%, indicating a strong safety profile for this noninvasive approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I clinical evaluation of near-simultaneous computed tomographic image-guided stereotactic body radiotherapy for spinal metastases. Chang, EL., Shiu, AS., Lii, MF., et al.[2022]

Dynamic tumor tracking-stereotactic body radiotherapy (DTT-SBRT) demonstrated a high local control rate of 95.2% for lung tumors after 2 years, indicating its efficacy in managing lung cancer.

The treatment was associated with low severe toxicity, with only 2.1% of patients experiencing grade 3 radiation pneumonitis, and no grade 4 or 5 toxicities reported, highlighting its safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multi-institutional phase II study on the safety and efficacy of dynamic tumor tracking-stereotactic body radiotherapy for lung tumors. Matsuo, Y., Hiraoka, M., Karasawa, K., et al.[2022]

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]

Advancements in imaging and predictive assays are paving the way for patient-specific biologically guided radiation therapy (BGRT), which could significantly improve treatment outcomes by tailoring therapies to individual responses.

The implementation of BGRT in clinical settings is expected to evolve over the next decade, with even partial adoption potentially leading to substantial improvements in how radiation therapy is delivered.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BGRT: biologically guided radiation therapy-the future is fast approaching! Stewart, RD., Li, XA.[2017]

Biology-guided radiotherapy (BgRT) is a promising new technique that allows real-time tracking of tumors during treatment, potentially enabling complete ablation of metastatic cancer.

This innovative approach combines PET-CT imaging with a linear accelerator to deliver targeted radiation more efficiently, which could improve patient outcomes and make advanced treatment more accessible.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biology-guided radiotherapy: redefining the role of radiotherapy in metastatic cancer. Shirvani, SM., Huntzinger, CJ., Melcher, T., et al.[2021]

Biology-guided radiation therapy uses biological and molecular imaging, like PET scans, to enhance the effectiveness of external beam radiotherapy by tailoring treatments to individual patient responses.

This approach has shown promise in various cancers, including thoracic, gastrointestinal, and hematologic malignancies, and advancements in imaging technology and radiotracers are expected to improve treatment outcomes further.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biology-Guided Radiation Therapy: An Evolving Treatment Paradigm. Ladbury, C., Eustace, N., Amini, A., et al.[2023]

In a study of 84 prostate cancer patients, 74% of metastatic lesions were found suitable for biology-guided radiotherapy (BgRT) using a 10-mm tracking zone, indicating a high potential for effective treatment targeting.

However, some lesions were adjacent to non-tumor tissues with PSMA uptake, such as the bladder and ureter, which may complicate BgRT and necessitate careful consideration during treatment planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Utility of Biology-Guided Radiotherapy to De Novo Metastases Diagnosed During Staging of High-Risk Biopsy-Proven Prostate Cancer. Gaudreault, M., Chang, D., Hardcastle, N., et al.[2022]

Biology-guided radiotherapy (BgRT) is a novel radiation therapy that combines PET-CT imaging with real-time tumor tracking, allowing for precise treatment of multiple tumors during a single session.

A comprehensive process map was developed by a multidisciplinary team, outlining 15 major subprocesses and 248 steps necessary for implementing BgRT, emphasizing the unique workflow requirements for safe and effective treatment delivery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A detailed process map for clinical workflow of a new biology-guided radiotherapy (BgRT) machine. Hwang, MS., Lalonde, R., Huq, MS.[2022]

References

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

Patient and Treatment Factors Associated With Improved Local Control and Survival in Oligometastatic Bone Disease: Results From a Large Single-Institution Experience Using Stereotactic Body Radiation Therapy. [2022]

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

A quantitative and comparative evaluation of stereotactic spine radiosurgery local control: proposing a consistent measurement methodology. [2022]

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

Phase I clinical evaluation of near-simultaneous computed tomographic image-guided stereotactic body radiotherapy for spinal metastases. [2022]

4. Ireland pubmed.ncbi.nlm.nih.gov

Multi-institutional phase II study on the safety and efficacy of dynamic tumor tracking-stereotactic body radiotherapy for lung tumors. [2022]

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

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

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

BGRT: biologically guided radiation therapy-the future is fast approaching! [2017]

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

Biology-guided radiotherapy: redefining the role of radiotherapy in metastatic cancer. [2021]

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

Biology-Guided Radiation Therapy: An Evolving Treatment Paradigm. [2023]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Utility of Biology-Guided Radiotherapy to De Novo Metastases Diagnosed During Staging of High-Risk Biopsy-Proven Prostate Cancer. [2022]

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

A detailed process map for clinical workflow of a new biology-guided radiotherapy (BgRT) machine. [2022]