Targeted Radiation Therapy for Brain Cancer

(CogRT Trial)

Recruiting at 2 trial locations

Overseen By Katie Lowe

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Disqualifiers: Pregnancy, Down's syndrome, Autism, others

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

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

338 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores ways to safely reduce the radiation dose to brain areas crucial for thinking and learning in children needing radiation therapy for brain-related tumors. It aims to determine if this approach can lessen the impact on cognitive abilities. The trial includes three groups: children newly diagnosed with brain or head and neck tumors, former childhood brain tumor patients who received radiation at least two years ago, and healthy children for comparison. Potential participants include children with a new brain tumor diagnosis who haven't completed radiation or those who had radiation over two years ago without recurrence. As an unphased trial, this study offers a unique opportunity to contribute to research that could improve future treatment options for children.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that this radiation therapy is safe for children?

Research shows that substructure-informed radiation therapy may target brain tumors while protecting areas crucial for thinking and learning. Patients who received this specialized treatment generally tolerated it well.

Studies have examined how different radiation doses affect brain health and quality of life. One study found that adjusting the radiation dose to specific brain regions might reduce side effects related to thinking and learning. This research aims to use these adjustments to maintain patients' quality of life during and after treatment.

Although more data is needed for broader conclusions, current findings suggest this treatment could be a safer option for children undergoing radiation therapy for brain tumors. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores a new approach to radiation therapy for brain cancer. Unlike traditional radiation, which often affects healthy brain tissue, this study uses substructure-informed radiation therapy. This method carefully targets specific brain substructures, potentially reducing damage to healthy areas and improving patient outcomes. By refining how radiation is delivered, this technique aims to enhance precision and effectiveness, offering hope for better quality of life and survival rates in patients with brain cancer.

What evidence suggests that this trial's radiation therapy could be effective for brain cancer?

Research has shown that higher doses of radiation to specific brain areas can lower quality of life and cause cognitive problems in children treated for brain tumors. Studies have found that adjusting radiation to avoid these critical brain regions might reduce these issues. In this trial, participants in Stratum A will receive substructure-informed radiation therapy, which considers these brain areas. Evidence suggests that children receiving targeted radiation may perform better on cognitive tests compared to those receiving standard radiation. These findings support the idea that targeted radiation could help protect children's cognitive abilities during brain tumor treatment. ^{2 3 4 6 7}

Who Is on the Research Team?

Sahaja Acharya, MD

Principal Investigator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Are You a Good Fit for This Trial?

This trial is for children and young adults aged 1 to <26 with new brain or head and neck tumors needing radiation therapy. It includes those who finished radiation at least two years ago without recurrence, and healthy kids for comparison.

Inclusion Criteria

I am between 5 and 25 years old and can undergo imaging tests without needing sedation.

I was diagnosed with a brain tumor before 26, had brain radiation over 2 years ago, and my tumor hasn't come back since.

I am between 1 and 25 years old with a brain tumor receiving radiation therapy.

Exclusion Criteria

STRATUM B: Inability to undergo neuro-cognitive testing, including children lacking English comprehension or with premorbid neurological/neurodevelopmental disorders such as Down's syndrome or autism

I am not pregnant, can undergo brain function tests, and do not have conditions like Down's syndrome or autism.

I have a major psychiatric, neurologic, or medical condition.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Patients undergo radiation therapy planned according to dose constraints to specific brain substructures

1 month

Neurocognitive Testing and MRI

Neurocognitive testing and MRI imaging are conducted to assess brain changes and cognitive outcomes

baseline to 5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of tumor recurrence and cognitive outcomes

up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Radiation Therapy

Trial Overview The study tests if targeting radiation more precisely to protect brain areas important for thinking can reduce learning impairments. Participants undergo neurocognitive testing and MRI scans to assess the impact of different radiation plans.

How Is the Trial Designed?

Group I: Stratum C (healthy controls matched to Stratum A) Experimental Treatment 2 Interventions

Healthy patients who are matched to Stratum A patients

Group II: Stratum B (patients ≥ 2 years after standard radiation therapy) Experimental Treatment 2 Interventions

Patients who completed radiation therapy under standard planning procedures ≥ 2 years ago.

Group III: Stratum A (new diagnosis, substructure informed radiation therapy) Experimental Treatment 3 Interventions

Patients will undergo radiation therapy which has been planned according to dose constraints to specific brain substructures.

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

Approved in European Union as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in United States as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Canada as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Japan as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in China as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Switzerland as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Who Is Running the Clinical Trial?

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Lead Sponsor

Trials

578

Recruited

33,600+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Clark Charitable Foundation

Collaborator

Trials

2

Recruited

410+

Published Research Related to This Trial

The combination of stereotactic radiosurgery (SRS) and whole-brain radiotherapy (WBRT) improves local tumor control and neurological function in patients with brain metastases, particularly benefiting those with a single metastasis, as it is associated with better survival compared to WBRT alone.

Current studies on SRS compared to other treatments like WBRT or neurosurgery show limited quality and inconclusive evidence, highlighting the need for more rigorous research to assess the effectiveness and safety of these interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Medical and health economic assessment of radiosurgery for the treatment of brain metastasis. Müller-Riemenschneider, F., Schwarzbach, C., Bockelbrink, A., et al.[2021]

In a study of 289 prostate cancer patients, hypofractionated proton beam therapy (PBT) showed no significant differences in acute adverse event rates or quality of life, as measured by the International Prostate Symptom Score (IPSS), compared to conventionally fractionated PBT.

The study evaluated patients treated with different doses (2.0, 2.5, and 3.0 Gy RBE per fraction) and found that factors like diabetes, age, and androgen deprivation therapy did not influence the IPSS outcomes, suggesting that hypofractionated PBT is a safe option without increased toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute toxicity and patient-reported symptom score after conventional versus moderately hypofractionated proton therapy for prostate cancer. Iizumi, T., Ishikawa, H., Sekino, Y., et al.[2022]

Radiation therapy is essential for treating brain tumors, utilizing various techniques to improve patient outcomes.

The review covers both traditional methods and advanced techniques like intensity-modulated radiotherapy and stereotactic radiosurgery, highlighting the evolution of treatment options available for effective tumor management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation techniques in neuro-oncology. Khuntia, D., Tomé, WA., Mehta, MP.[2021]

Patients with high-risk prostate cancer treated with image-guided intensity-modulated radiotherapy (IG-IMRT) experienced significantly lower rates of gastrointestinal (GI) toxicity (5.8%) compared to those treated with 3D conformal radiotherapy (3DCRT) (57.3%), indicating that IG-IMRT is a safer option.

Both IG-IMRT and 3DCRT showed similar rates of biochemical progression-free survival at 3 years (90.3% for IG-IMRT vs. 86.0% for 3DCRT), suggesting that while IG-IMRT reduces toxicity, it does not compromise treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improvement in toxicity in high risk prostate cancer patients treated with image-guided intensity-modulated radiotherapy compared to 3D conformal radiotherapy without daily image guidance. Sveistrup, J., af Rosenschöld, PM., Deasy, JO., et al.[2021]

Intensity-modulated radiation therapy (IMRT) resulted in significantly lower rates of acute and late genitourinary (GU) and gastrointestinal (GI) toxicity compared to (125)I seed implants, with 3-year rates of 3.5% GU and 2.4% GI toxicity for IMRT versus 19.2% GU and 7.7% GI for (125)I.

Both treatments showed similar biochemical failure rates, with IMRT having a 4-year freedom from failure rate of 99.5% compared to 93.5% for (125)I, indicating that while both are effective, IMRT may be safer with fewer side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison of acute and chronic toxicity for men with low-risk prostate cancer treated with intensity-modulated radiation therapy or (125)I permanent implant. Eade, TN., Horwitz, EM., Ruth, K., et al.[2022]

Image-guided radiation therapy (IGRT) has evolved significantly and is now widely used in routine clinical practice, emphasizing the importance of quality and patient safety in its application across various treatment techniques and anatomical sites.

The American Society for Radiation Oncology recommends a comprehensive quality-assurance program and an interdisciplinary team approach to ensure IGRT is performed safely and effectively, highlighting the need for ongoing updates to practice guidelines as technology advances.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality and Safety Considerations in Image Guided Radiation Therapy: An ASTRO Safety White Paper Update. Qi, XS., Albuquerque, K., Bailey, S., et al.[2023]

In a study of 192 patients with localized prostate cancer, using prostate-based IGRT (P-IGRT) resulted in significantly lower acute gastrointestinal toxicities compared to bony structure-based IGRT (B-IGRT), with rates of 3% versus 11%.

Both P-IGRT and B-IGRT showed similar prostate-specific antigen failure-free survival rates at 3 years (95.5% for P-IGRT and 92.7% for B-IGRT), indicating that P-IGRT can reduce toxicity without compromising tumor control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Decreased acute toxicities of intensity-modulated radiation therapy for localized prostate cancer with prostate-based versus bone-based image guidance. Nakamura, K., Mizowaki, T., Inokuchi, H., et al.[2018]

Intensity-modulated stereotactic radiotherapy (IMSRT) provides better conformity and coverage for planning target volumes (PTV) compared to stereotactic conformal radiotherapy (SCRT), especially for irregular and multifocal lesions, based on a study of 10 patients.

IMSRT also offers improved sparing of organs at risk (OAR), resulting in lower doses to these critical areas, although it may increase the volume of normal tissue receiving a low dose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity-modulated stereotactic radiotherapy vs. stereotactic conformal radiotherapy for the treatment of meningioma located predominantly in the skull base. Baumert, BG., Norton, IA., Davis, JB.[2022]

In a study of 22 patients with locally advanced rectal cancer, image-guided radiotherapy (IGRT) led to complete surgical resection in all cases, with 32% of patients showing no residual tumor after treatment.

The treatment was associated with minimal toxicity, although one patient experienced severe side effects likely due to an overdose of capecitabine, suggesting that IGRT is a promising approach for reducing complications in rectal cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of image-guided radiotherapy for locally advanced rectal cancer. Nguyen, NP., Ceizyk, M., Almeida, F., et al.[2011]

Radiotherapy is an important treatment option for both malignant and benign intracranial tumors, often used alongside neurosurgery to improve outcomes.

Stereotactic radiosurgery, particularly using gamma knife technology, is a highly precise method for irradiating tumors and is increasingly combined with systemic therapies to effectively treat metastatic lesions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiosurgical techniques for the treatment of brain neoplasms: A short review. Velnar, T., Bosnjak, R.[2020]

Targeted radiotherapy presents a promising alternative to traditional external beam radiotherapy for malignant brain tumors, as it aims to increase the precision of radiation delivery to tumor cells while minimizing damage to surrounding healthy brain tissue.

This approach could potentially enhance treatment efficacy by focusing on tumor cells specifically, reducing the risk of adverse effects associated with excessive radiation exposure to normal central nervous system tissues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted radiotherapy of brain tumours. Zalutsky, MR.[2022]

Radiation oncologists are exploring various innovative approaches, such as interstitial implants and stereotactic radiosurgery, to enhance cure rates for primary brain tumors while aiming to reduce long-term side effects.

These new radiation techniques must be integrated into a comprehensive treatment plan that includes other therapies to effectively manage primary malignant brain tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improving radiotherapy for brain tumors. Woo, SY., Maor, MH.[2005]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12511131/

Impact of substructure radiation dose on health-related quality ... Conclusion. Higher radiation doses to specific brain substructures were associated with poorer HRQoL outcomes after PBT. Minimizing dose to ...

2. redjournal.org redjournal.org/article/S0360-3016(25)06015-8/abstract

Association Between Brain Substructure Dose and ... Radiation therapy may cause cognitive deficits in pediatric brain tumor survivors (PBTS). Scholastic data provide prediagnostic measurements ...

3. hopkinsmedicine.org hopkinsmedicine.org/brain-tumor/clinical-trials

Brain Tumor Clinical Trials Clinical trials often help improve outcomes, especially for patients with aggressive tumors. View a list of studies for patients with brain tumors.

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0360301624034060

Evaluating Scholastic Achievement in Pediatric Brain ... Forty percent received craniospinal irradiation, and 56% received chemotherapy. Post-RT PBTS had 21 times the odds of receiving accommodations (P = .006), twice ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40691995/

Association Between Brain Substructure Dose and ... We present the first ever report evaluating associations between dosimetry and scholastic performance. We demonstrate a novel method using ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05658731

Cognitive Outcomes After Brain Substructure-informed ... The goal of this trial is to determine whether it is possible to minimize radiation dose to parts of the brain that are important for thinking and learning ...

7. withpower.com withpower.com/trial/targeted-radiation-therapy-for-brain-cancer-12f47

Targeted Radiation Therapy for Brain Cancer (CogRT Trial) The goal of this trial is to determine whether it is possible to minimize radiation dose to parts of the brain that are important for thinking and learning ...