Fractionated Stereotactic Radiation Therapy for Brain Cancer

Recruiting at 1 trial location

Overseen By Nitin Ohri, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Albert Einstein College of Medicine

Must not be taking: Chemotherapy, Targeted agents

Disqualifiers: Leptomeningeal metastases, Small cell lung cancer, Uncontrolled illness, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

43 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method of delivering radiation therapy to individuals with brain cancer that has metastasized. Researchers aim to determine the safest dose of Fractionated Stereotactic Radiation Therapy, a type of targeted radiation, for treating brain tumors. This will help plan future studies to evaluate the effectiveness of different treatment schedules. Suitable candidates have brain tumors between 3 and 6 cm that have not been fully removed by surgery and have undergone previous cancer treatments. As a Phase 1 trial, this research focuses on understanding the treatment's effects in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that you cannot plan for chemotherapy or targeted agents during treatment. Hormonal and bone supportive therapies can be continued.

What prior data suggests that Fractionated Stereotactic Radiation Therapy is safe for treating brain metastases?

Studies have shown that Fractionated Stereotactic Radiation Therapy (FSRT) is generally well-tolerated by patients with brain metastases. Research indicates that FSRT provides a high rate of local control, effectively targeting and treating cancer without spreading. Importantly, it carries a minimal risk of severe side effects, making it a promising option for many patients. One study found that FSRT is linked to a lower chance of radiation necrosis, which is damage to brain tissue from radiation, compared to other similar treatments. Overall, FSRT demonstrates good safety results and is considered effective for treating brain metastases. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment for brain cancer?

Fractionated Stereotactic Radiation Therapy (FSRT) is unique because it uses a precise method to deliver radiation in smaller doses over multiple sessions, potentially reducing damage to healthy brain tissue compared to traditional whole-brain radiation therapy. Unlike most treatments that use a fixed radiation dose, FSRT employs a continuous reassessment methodology to tailor the maximum tolerated dose for each patient based on the side effects experienced by previous participants. This personalized approach could lead to more effective treatment with fewer side effects, which is why researchers are excited about its potential.

What evidence suggests that Fractionated Stereotactic Radiation Therapy might be an effective treatment for brain cancer?

Research has shown that Fractionated Stereotactic Radiation Therapy (FSRT), the treatment under study in this trial, is a promising approach for brain metastases, which are cancerous growths in the brain. Studies have found that FSRT effectively targets and controls cancer in the brain with few serious side effects. For patients with 1-4 brain metastases, higher doses of FSRT have proven both possible and effective. However, these higher doses might increase the risk of radiation necrosis, which is damage to brain tissue caused by radiation. Overall, FSRT is considered a safe and effective treatment for brain cancer, with good results in controlling the cancer locally. ^{1 5 6 7 8}

Who Is on the Research Team?

Madhur Garg, MD

Principal Investigator

Montefiore Medical Center

Are You a Good Fit for This Trial?

This trial is for adults with brain metastases larger than 3 cm but smaller than 6 cm, who haven't had surgery on the lesion. They can have had whole brain radiation before and may have other lesions treated separately. Participants need to be relatively active (Karnofsky ≥60 or ECOG ≤2), not pregnant, and expected to live more than 3 months.

Inclusion Criteria

Women of childbearing potential and male participants must practice adequate contraception

History/Physical examination within 30 days prior to registration

You are able to perform daily activities without much difficulty.

Exclusion Criteria

You have brain tumors caused by certain types of cancer.

You cannot have metal implants that are not safe for MRI scans. If you have MRI-safe implants, you can still participate.

You have a serious health condition that is not being managed well, like heart problems or seizures.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Participants receive Fractionated Stereotactic Radiation Therapy (FSRT) to determine the Maximum Tolerated Dose (MTD)

3-12 fractions

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Fractionated Stereotactic Radiation Therapy

Trial Overview The study tests Fractionated Stereotactic Radiation Therapy (FSRT) to find the highest dose patients can tolerate without severe side effects. This Phase I trial will set the stage for future studies by establishing safe dosage levels of FSRT in treating brain metastases.

How Is the Trial Designed?

Group I: Fractionated Stereotactic Radiation Therapy (FSRT) Experimental Treatment 1 Intervention

This study is unique in that it employs a continuous reassessment methodology (CRM) to determine the Maximum Tolerated Dose. Information for the proper dose level for each subsequent patient enrolled will be determined based on DLTs from previous patients enrolled in the trial.

Fractionated Stereotactic Radiation Therapy is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Fractionated Stereotactic Radiation Therapy for:

• Brain metastases

Approved in European Union as Fractionated Stereotactic Radiotherapy for:

• Brain metastases

Approved in Canada as Fractionated Stereotactic Radiation Therapy for:

• Brain metastases

Approved in Japan as Fractionated Stereotactic Radiation Therapy for:

• Brain metastases

Who Is Running the Clinical Trial?

Albert Einstein College of Medicine

Lead Sponsor

Trials

302

Recruited

11,690,000+

Published Research Related to This Trial

Fractionated stereotactic radiation therapy (FSRT) showed an impressive 12-month local control rate of 86% for brain metastases, with even higher rates (95%) for tumors smaller than 3 cm, indicating its efficacy in managing these conditions.

The treatment was associated with minimal severe toxicity, with only 6% of patients experiencing grade 4 toxicity, and no irreversible severe side effects, making FSRT a safe option for patients who may not tolerate single-fraction treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fractionated stereotactic radiation therapy for intact brain metastases. Marcrom, SR., McDonald, AM., Thompson, JW., et al.[2022]

In a study of 75 patients treated with fractionated stereotactic radiotherapy (FSRT) for nonfunctional pituitary adenomas, both early (adjuvant) and delayed (on-progression) treatments showed excellent tumor control rates of around 94-95%.

Delaying FSRT until tumor progression resulted in a longer time before new endocrinopathies developed, suggesting that monitoring the tumor before treatment may help maintain hormonal function while still effectively controlling the tumor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early versus Delayed Fractionated Stereotactic Radiotherapy for Nonfunctioning Pituitary Adenoma. Sathe, AV., Siu, A., Kang, KC., et al.[2023]

Fractionated stereotactic radiotherapy (FSRT) is a safe and effective treatment for cavernous sinus meningiomas, achieving a local progression-free survival rate of 93% over a median follow-up of 50 months among 30 patients.

The treatment led to improvement in preexisting neurological symptoms for 50% of patients, with only a small number experiencing late radiation toxicity, indicating good tolerance and minimal cognitive decline post-treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fractionated stereotactic radiotherapy in the treatment of exclusive cavernous sinus meningioma: functional outcome, local control, and tolerance. Brell, M., Villà, S., Teixidor, P., et al.[2018]

In a study of 69 patients with 1-4 brain metastases, higher-dose fractionated stereotactic radiotherapy (FSRT) showed promising local control rates of 81% at 1 year and 63% at 2 years, along with overall survival rates of 66% and 43%, respectively.

While higher doses (63-66.7 Gy12) did not improve local control or overall survival compared to lower doses (49.6-57 Gy12), they were associated with a higher risk of radiation necrosis, indicating a need for careful dose management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment Outcomes After Higher-dose Fractionated Stereotactic Radiotherapy (FSRT) Alone for 1-4 Brain Metastases. Johannwerner, L., Werner, EM., Janssen, S., et al.[2023]

In a study of 13 patients with parasellar meningiomas treated with fractionated stereotactic radiotherapy (FSRT), 12.5% of eyes showed improved visual acuity, while 75% remained stable, indicating a generally positive outcome.

FSRT was found to be safe, as no adverse visual outcomes were reported, and over half of the eyes (57%) experienced improvements in visual field, suggesting its efficacy in treating tumors near critical structures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fractionated stereotactic radiotherapy for parasellar meningiomas: a preliminary report of visual outcomes. Behbehani, RS., McElveen, T., Sergott, RC., et al.[2018]

Fractionated stereotactic radiotherapy (FSRT) demonstrated high local control rates and low morbidity in treating small intracranial malignancies, with a median survival of 21.2 months for patients without extracranial tumors.

The study involved 80 patients with 121 tumors, showing that while FSRT is effective, patients with certain risk factors may require smaller radiation doses to minimize potential late radiation injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fractionated stereotactic radiotherapy of small intracranial malignancies. Tokuuye, K., Akine, Y., Sumi, M., et al.[2022]

Fractionated stereotactic radiation therapy (FSRT) based on biological effective dose (BED) demonstrated a high local control rate of 96.3% at 6 months and 94.5% at 12 months for brain metastases from non-small cell lung cancer (NSCLC), indicating its efficacy in managing these tumors.

The treatment showed acceptable toxicity, with only 2% of patients experiencing progressive radiation injury, which improved with hyperbaric oxygen therapy, suggesting that FSRT is a promising option for patients with brain metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical outcomes of biological effective dose-based fractionated stereotactic radiation therapy for metastatic brain tumors from non-small cell lung cancer. Matsuyama, T., Kogo, K., Oya, N.[2022]

Fractionated stereotactic radiotherapy (FSRT) is a safe and effective treatment for brain metastases of any size, showing excellent local control with a 12-month local failure rate of 17.8% overall.

In a study of 60 patients treated with FSRT, the median survival was 20.5 months, and the risk of radionecrosis was relatively low at 7.1%, indicating favorable toxicity outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes of Hypofractionated Stereotactic Radiotherapy for Small and Moderate-Sized Brain Metastases: A Single-Institution Analysis. Yan, M., Zalay, O., Kennedy, T., et al.[2022]

The study analyzed 24 treatment plans for 23 patients using fractionated stereotactic radiotherapy (FSRT) and found that the treatment plans achieved clinically acceptable quality indices, indicating effective management of brain metastases.

Key metrics such as the Radiation Therapy Oncology Group conformity index (mean 0.942) and the Paddick conformity index (mean 0.824) demonstrated that FSRT can be effectively tailored for various tumor volumes, ensuring safety and efficacy in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Plan Quality Assessment of Fractionated Stereotactic Radiotherapy Treatment Plans in Patients With Brain Metastases. Simon, M., Papp, J., Csiki, E., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5707424/

Fractionated stereotactic radiation therapy for intact brain ... FSRT for brain metastases appears to demonstrate a high rate of local control with minimal risk of severe toxicity.

2. sciencedirect.com sciencedirect.com/science/article/pii/S2405630824001708

Fractionated stereotactic radiotherapy of brainstem ... FSRT for BSM is as an effective and safe treatment approach with high LC rates and reasonable neurological toxicity despite the poor prognosis.

3. ar.iiarjournals.org ar.iiarjournals.org/content/43/6/2757

Treatment Outcomes After Higher-dose Fractionated ... Higher-dose FSRT appears feasible and effective in patients with 1-4 brain metastases. BED 63-66.7 Gy 12 may not improve LC and OS but may increase RN risk.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03726359

Phase I Study of Fractionated Stereotactic Radiation ... The results of this study will be used to plan future Phase II/III studies to determine the efficacy of different dose fractionation schedules of FSRT. The ...

5. ro-journal.biomedcentral.com ro-journal.biomedcentral.com/articles/10.1186/s13014-023-02277-6

Fractionated stereotactic radiotherapy of brain metastases Conclusions. FSRT in 6 fractions of 5 Gy seems to be an effective treatment with an acceptable local control for patients with brain metastases ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S258953702500121X

Efficacy and safety of online adaptive magnetic resonance- ... Online adaptive FSRT using a 1.5 T MR-Linac has demonstrated effectiveness and good tolerability for BMs in patients with NSCLC.

7. frontiersin.org frontiersin.org/journals/oncology/articles/10.3389/fonc.2024.1471004/full

Analysis of linear accelerator-based fractionated ... Results: Results as of December 2023 showed median intracranial progression-free survival (iPFS) at 12.4 months, with median overall survival (OS) not reached ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT02187822

Fractionated Stereotactic Radiotherapy (FSRT) in ... The main purpose of this study is to see whether addition of TPI 287 to FSRT is safe and tolerable. Researchers also want to find out if adding TPI 287 to ...