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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method of delivering radiation treatment to individuals with brain cancer. It targets patients with brain tumors of specific sizes (2.1-4.0 cm and 4.1-6.0 cm) that have metastasized from other body parts. The trial aims to determine if administering higher doses of radiation in fewer sessions, known as Dose Escalated Five Fraction Stereotactic Radiosurgery, is safe and effective. Candidates for this trial include those diagnosed with brain metastases and up to 10 tumors. As an unphased trial, it provides a unique opportunity for patients to explore innovative treatment options that could potentially enhance their quality of life.

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 prior data suggests that this dose escalated five fraction stereotactic radiosurgery is safe for treating brain metastases?

Research has shown that stereotactic radiosurgery, a focused radiation treatment, is generally well-tolerated by patients with brain metastases. In past studies, patients underwent five sessions of this treatment, known as fractionated stereotactic radiosurgery, with favorable safety outcomes.

One study found that most patients tolerated the treatment without serious side effects. Although some experienced radiation necrosis, or damage to healthy tissue from radiation, the overall safety was deemed acceptable. Another study demonstrated that the treatment was effective for patients with multiple brain tumors, suggesting it is safe for more complex cases.

While some patients may experience mild to moderate side effects, the treatment remains safe for ongoing research and medical use. Patients should consult their healthcare provider about potential risks and benefits to determine if joining a clinical trial is appropriate. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about dose escalated five fraction stereotactic radiosurgery for brain cancer because it offers a new way to potentially enhance the effectiveness of radiation treatment. Unlike the standard approach where all tumors are treated with the same radiation dose, this method focuses on delivering a higher radiation dose specifically to the single largest tumor. This targeted escalation could improve treatment outcomes by intensifying the attack on the most problematic tumor, potentially leading to better control of brain metastases. With this tailored strategy, there's hope for more effective management of brain cancer, especially for tumors between 2.1 and 6.0 cm in diameter.

What evidence suggests that dose escalated five fraction stereotactic radiosurgery is effective for brain metastases?

Research has shown that stereotactic radiosurgery (SRS) holds promise for treating cancer that has spread to the brain. In this trial, participants will receive dose-escalated five fraction SRS based on the size of their largest tumor. Studies have found that a moderately high dose of SRS can effectively stop cancer growth in the treated area. Specifically, patients who received SRS for one to four brain tumors lived for about 7.5 months on average, suggesting the treatment might extend life for some patients. Additionally, SRS effectively controls the tumors it targets, preventing their growth. ^{2 4 5 6 7}

Who Is on the Research Team?

John B. Fiveash

Principal Investigator

University of Alabama at Birmingham

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: 4.1-6.0 cm diameter Experimental Treatment 3 Interventions

Patients will undergo dose escalated five fraction stereotactic radiosurgery for diagnosed brain metastases. 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. Starting dose level 6 Gy x 5 fractions.

Group II: 2.1-4.0 cm diameter Experimental Treatment 3 Interventions

Patients will undergo dose escalated five fraction stereotactic radiosurgery for diagnosed brain metastases. 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. Starting dose level 7 Gy x 5 fractions

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

Published Research Related to This Trial

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9955428/

Five-Fraction Stereotactic Radiotherapy for Brain Metastases ... Purpose: To determine the safety and outcome profile of five-fraction stereotactic radiotherapy (FSRT) for brain metastases (BM), ...

2. withpower.com withpower.com/trial/phase-neoplasm-metastasis-6-2018-0222f

High-Dose Stereotactic Radiation for Brain Cancer ... 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 ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0360301611033888

Treatment of Five or More Brain Metastases With ... The median OS after SRS was 7.5 months. The median KPS was 80 (range, 60–100). A KPS of ≥80 significantly influenced OS (median OS, 4.8 months for KPS ≤70 vs.

4. advancesradonc.org advancesradonc.org/article/S2452-1094(23)00230-0/fulltext

Stereotactic Radiosurgery in the Management of Brain ... Dosimetric predictors of symptomatic radiation necrosis after five-fraction radiosurgery for brain metastases. Radiother Oncol. 2021; 156:181 ...

5. advancesradonc.com advancesradonc.com/article/S2452-1094(17)30111-2/fulltext

Fractionated stereotactic radiation therapy for intact brain ... The median overall survival was 7 months with a 6- and 12-month estimate of overall survival of 63% and 29%, respectively. Local progression was observed in 10 ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03412812

A Dose Escalation Trial of Five Fraction Stereotactic ... This study looks at dose escalation treatment in patients diagnosed with brain metastases. Treatment involve five fraction stereotactic radiotherapy for ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4630352/

Efficacy and Safety of Fractionated Stereotactic Radiosurgery ... The median OS was 16 months, and the estimated OS rates at 6, 12 and 18 months were 81.1%, 56.8%, and 40.7%, respectively. Of 21 patients who died, 10 (47.6%) ...