High-Dose Stereotactic Radiation for Brain Cancer

(RAD1705 Trial)

Overseen By John B Fiveash, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Alabama at Birmingham

Disqualifiers: Surgical resection, Radiation history, others

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

Compensation: Varies

Number of Visits: 5

Duration: 1 week

13 Participants Needed

Trial Summary

What is the purpose of this trial?

This study looks at dose escalation for five fraction stereotactic radiotherapy for patients diagnosed with brain metastases with tumors 2.1-4.0 cm in diameter or 4.1-6.0 cm in diameter.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have received systemic therapy (treatment affecting the whole body) within one week of the planned radiation treatment, except for hormonal agents.

What data supports the effectiveness of the treatment Dose Escalated Five Fraction Stereotactic Radiosurgery for brain cancer?

Research on similar treatments, like stereotactic radiosurgery for brain metastases, shows that carefully selected high-dose radiation can effectively control tumors while minimizing complications. Fractionated regimens, which spread the radiation dose over several sessions, are suggested to improve outcomes by reducing side effects compared to single high-dose treatments. ^{1 2 3 4 5}

Is high-dose stereotactic radiation generally safe for treating brain conditions?

High-dose stereotactic radiation, also known as radiosurgery, is generally well tolerated when a small volume of the brain is treated, but there is a risk of radiation reactions, especially if larger volumes are involved. Safety data from various studies suggest that careful dose selection and treatment planning are crucial to minimize complications, and fractionated regimens (dividing the total dose into smaller doses over several sessions) may offer improved safety for treating recurrent brain tumors. ^{1 2 4 6 7}

How does the treatment Dose Escalated Five Fraction Stereotactic Radiosurgery differ from other treatments for brain cancer?

This treatment is unique because it uses a high-dose, focused radiation technique delivered in five sessions, which allows for precise targeting of brain tumors while minimizing damage to surrounding healthy tissue. Unlike traditional single-session radiosurgery, this approach may reduce the risk of side effects and improve tumor control by allowing for dose escalation tailored to the tumor's size and location. ^{1 3 4 5 8}

Research Team

John B. Fiveash

Principal Investigator

University of Alabama at Birmingham

Eligibility Criteria

This trial is for adults over 18 with a confirmed cancer diagnosis and up to 10 brain metastases, as seen on an MRI. They must have a Karnofsky performance status of at least 60, indicating they can care for themselves. Participants need to consent in writing but cannot join if they've had surgery or prior radiation on the tumor, previous whole-brain irradiation, can't undergo MRI, received certain treatments within a week before the study starts, or have another large tumor.

Inclusion Criteria

All patients must have histologically confirmed malignancy

All patients must have imaging suggestive of one or more brain metastases

I am older than 18 years.

Exclusion Criteria

I have had whole brain radiation before.

My second tumor is not larger than 3 cm.

My tumor has been treated with radiation before.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo dose escalated five fraction stereotactic radiosurgery for brain metastases

1 week

5 visits (in-person)

Follow-up

Participants are monitored for safety, effectiveness, and toxicity after treatment

1-2 years

Treatment Details

Interventions

• Dose Escalated Five Fraction Stereotactic Radiosurgery

Trial Overview The study tests increasing doses of stereotactic radiosurgery delivered in five sessions for treating brain tumors that are between 2.1-6.0 cm in diameter. It aims to find out how much radiation can be safely given to shrink these tumors while sparing healthy tissue.

Participant Groups

Group I: Dose Escalated 5 Fraction Stereotactic Radiosurgery Experimental Treatment 1 Intervention

Patients will undergo dose escalated five fraction stereotactic radiosurgery for diagnosed brain metastases. Tumors must fall into one of two categories: 2.1-4.0cm diameter or 4.1-6.0 cm diameter. Only single largest tumor will be treated with dose escalation. All other tumors (if present) will be treated with standard of care five fraction stereotactic radiosurgery.

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

Findings from Research

In a study involving 20 patients with recurrent malignant gliomas, hypofractionated stereotactic radiotherapy (H-SRT) demonstrated a low toxicity profile, with no grade 3 toxicities or reoperations required due to treatment-related complications.

The study found that higher total doses of H-SRT (30 Gy and 35 Gy) were associated with a significantly better response rate (79%) compared to lower doses, suggesting that dose escalation could enhance treatment efficacy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I dose escalation study of hypofractionated stereotactic radiotherapy as salvage therapy for persistent or recurrent malignant glioma. Hudes, RS., Corn, BW., Werner-Wasik, M., et al.[2022]

Moderately dosed stereotactic radiosurgery (SRS) for one to four brain metastases showed a median overall survival of 7.5 months, with high local brain control rates of 87% at 6 months and 79% at 12 months, indicating its efficacy in treating limited brain metastases.

The study suggests that initial SRS alone can be a safe treatment option, as only 22% of patients required additional whole-brain radiotherapy, and significant predictors of survival included the time between the primary diagnosis and brain metastases, as well as the volume of the treated metastasis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcome of moderately dosed radiosurgery for limited brain metastases. Report of a single-center experience. Meisner, J., Meyer, A., Polivka, B., et al.[2021]

Stereotactic radiosurgery has been successfully used for over 40 years to treat cerebral arteriovenous malformations, achieving complete obliteration rates of 30-50% after 1 year and 72-90% after 2 years, highlighting its efficacy based on patient selection.

Radiosurgery is also effective for treating acoustic neurinomas and pituitary tumors, with over 90% tumor growth control and approximately 50% hearing preservation, making it a noninvasive alternative to traditional surgery with lower morbidity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic radiation therapy and radiosurgery. Ostertag, CB.[2018]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Radiosurgical dose selection for brain metastasis. [2012]

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

Fractionated regimens for stereotactic radiotherapy of recurrent tumors in the brain. [2019]

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

Stereotatic radiosurgery of 468 brain metastases [2022]

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

A phase I dose escalation study of hypofractionated stereotactic radiotherapy as salvage therapy for persistent or recurrent malignant glioma. [2022]

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

LINAC radiosurgery as single treatment in cerebral metastases. [2018]

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

The influence of volume on the tolerance of the brain to radiosurgery. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

Outcome of moderately dosed radiosurgery for limited brain metastases. Report of a single-center experience. [2021]

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

Stereotactic radiation therapy and radiosurgery. [2018]