Lower Radiotherapy Dose for Brain Tumors

Recruiting at 101 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Children's Oncology Group

Disqualifiers: Pregnancy, Breastfeeding, Prior tumor therapy, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 13

240 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a lower dose of radiotherapy after chemotherapy can effectively treat brain tumors called CNS germinomas in children, with fewer long-term side effects. The treatments combine chemotherapy drugs, Carboplatin and Etoposide, followed by a reduced dose of radiation therapy using techniques like 3-Dimensional Conformal Radiation Therapy (3D-CRT) or Intensity-Modulated Radiation Therapy (IMRT). Researchers aim to determine if this approach can eliminate the tumors while minimizing harm. Children diagnosed with CNS germinomas, including those with specific tumor markers or brain involvement, might be suitable candidates for this trial. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you have a seizure disorder, you can participate if your condition is well controlled with anticonvulsants.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that both 3-Dimensional Conformal Radiation Therapy (3D-CRT) and Intensity-Modulated Radiation Therapy (IMRT) are generally well-tolerated by patients. IMRT offers particular benefits by targeting tumors more precisely, often resulting in fewer side effects compared to other radiation therapies.

For example, one study found that IMRT delivered lower radiation doses to healthy brain tissue, reducing the risk of side effects such as headaches or cognitive issues. Similarly, 3D-CRT is preferred over older methods because it shapes the radiation beams to fit the tumor, minimizing exposure to nearby healthy tissue.

Regarding chemotherapy, Carboplatin is generally better tolerated than Cisplatin, potentially causing fewer severe side effects like kidney damage or hearing loss. Etoposide, another chemotherapy drug used in the trial, has its own potential side effects but remains a standard treatment that has been used for many years.

As this trial is in Phase 2, earlier studies have shown some evidence of safety, but more data is needed to fully understand their safety. Participants should discuss any concerns with their healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for brain tumors because they aim to reduce radiation exposure while maintaining effectiveness. Unlike standard treatments that often use higher doses of radiation, this approach utilizes 3-Dimensional Conformal Radiation Therapy (3D-CRT) and Intensity-Modulated Radiation Therapy (IMRT) to precisely target tumors, potentially reducing side effects. Additionally, combining these radiation techniques with chemotherapy drugs like carboplatin and etoposide could enhance treatment outcomes. This innovative strategy seeks to improve patient quality of life by minimizing radiation-related damage to healthy brain tissue.

What evidence suggests that this trial's treatments could be effective for CNS germinomas?

Research has shown that using lower doses of radiation therapy with chemotherapy might effectively treat CNS germinomas, a type of brain tumor, with fewer long-term side effects. In this trial, participants will receive either Three-Dimensional Conformal Radiation Therapy (3D-CRT) or Intensity-Modulated Radiation Therapy (IMRT) as part of their treatment. Three-Dimensional Conformal Radiation Therapy (3D-CRT) has successfully controlled tumors, with 87% of patients experiencing no tumor return after five years and 97% surviving overall for intracranial (inside the skull) tumors. Intensity-Modulated Radiation Therapy (IMRT) is more precise, potentially reducing harm to nearby healthy tissue compared to 3D-CRT. IMRT has demonstrated a high success rate of 93% in controlling similar brain tumors over five years. In this trial, the chemotherapy drug carboplatin stops or slows tumor growth, while etoposide kills cancer cells by blocking an enzyme they need to divide. Together, these treatments offer a promising way to treat CNS germinomas while minimizing potential side effects. ^{2 4 6 7 8}

Who Is on the Research Team?

Mohamed S Abdelbaki

Principal Investigator

Children's Oncology Group

Are You a Good Fit for This Trial?

This trial is for children and young adults aged 3 to less than 30 with CNS germinoma, a type of brain tumor. It includes those newly diagnosed, with certain levels of specific markers in their blood or CSF, and can have tumors in various brain regions or with spread within the central nervous system. Participants need confirmed diagnoses via imaging or pathology and must be able to perform daily activities.

Inclusion Criteria

I have had a spinal fluid test before joining the study, after any surgery and spine MRI.

Patients must be enrolled, and protocol therapy must begin, no later than 31 days after definitive surgery or clinical diagnosis, whichever is later

My cancer is a mix of germinoma and mature teratoma.

Exclusion Criteria

Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation

All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

My cancer does not have specific malignant features listed as exclusion criteria.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Induction

All patients receive carboplatin and etoposide chemotherapy over multiple cycles

12 weeks

4 cycles, each with multiple visits

Radiation Therapy

Patients undergo radiation therapy based on their assigned stratum

3-5 weeks

5 visits per week

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 120 months

Every 3 months for 12 months, every 4 months for 24 months, then annually

What Are the Treatments Tested in This Trial?

Interventions

• 3-Dimensional Conformal Radiation Therapy
• Intensity-Modulated Radiation Therapy

Trial Overview The study tests if lower doses of radiotherapy after chemotherapy (using Carboplatin and Etoposide) are effective for treating CNS germinomas in children. The goal is to see if this approach reduces long-term side effects while still eliminating cancer cells. Techniques include advanced radiation therapy methods alongside surgery, MRI monitoring, lumbar puncture, biospecimen collection, and questionnaires.

How Is the Trial Designed?

Group I: Stratum VII (carboplatin, etoposide, 3D-CRT, IMRT) Experimental Treatment 8 Interventions

Patients receive carboplatin IV over 15-60 minutes on day 1 and etoposide IV over 90-120 minutes on days 1-3 of each cycle. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients with basal ganglia and thalamic germinoma with normalization of markers who fail to achieve CR who do not undergo second-look surgery undergo 3DRT or IMRT QD 5 days a week for 24 days. Patients undergo MRI and optional blood and tissue sample collection throughout the study. Patients may undergo LP for CSF sample collection during screening and follow up.

Group II: Stratum VI (carboplatin, etoposide, 3D-CRT, IMRT, surgery) Experimental Treatment 9 Interventions

Patients receive carboplatin IV over 15-60 minutes on day 1 and etoposide IV over 90-120 minutes on days 1-3 of each cycle. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients with basal ganglia and thalamic germinoma achieving CR undergo 3DRT or IMRT QD 5 days a week for 20 days. Patients with basal ganglia and thalamic germinoma and normalization of markers who fail to achieve CR may undergo second-look surgery. Patients found to have mature teratoma or non-viable tumor undergo 3DRT or IMRT QD 5 days a week for 20 days. Patients undergo MRI and optional blood and tissue sample collection throughout the study. Patients may undergo LP for CSF sample collection during screening and follow up.

Group III: Stratum V (carboplatin, etoposide, 3D-CRT, IMRT) Experimental Treatment 8 Interventions

Patients receive carboplatin IV over 15-60 minutes on day 1 and etoposide IV over 90-120 minutes on days 1-3 of each cycle. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients with metastatic germinoma with normalization of markers who fail to achieve CR who do not undergo second-look surgery undergo 3DRT or IMRT QD 5 days a week for 24 days. Patients undergo MRI and optional blood and tissue sample collection throughout the study. Patients may undergo LP for CSF sample collection during screening and follow up.

Group IV: Stratum IV (carboplatin, etoposide, 3D-CRT, IMRT, surgery) Experimental Treatment 9 Interventions

Patients receive carboplatin IV over 15-60 minutes on day 1 and etoposide IV over 90-120 minutes on days 1-3 of each cycle. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients with metastatic germinoma achieving CR undergo 3DRT or IMRT QD 5 days a week for 20 days. Patients with metastatic germinoma and normalization of markers who fail to achieve CR may undergo second-look surgery. Patients found to have mature teratoma or non-viable tumor undergo 3DRT or IMRT QD 5 days a week for 20 days. Patients undergo MRI and optional blood and tissue sample collection throughout the study. Patients may undergo LP for CSF sample collection during screening and follow up.

Group V: Stratum III (carboplatin, etoposide, 3D-CRT, IMRT) Experimental Treatment 8 Interventions

Patients receive carboplatin IV over 15-60 minutes on day 1 and etoposide IV over 90-120 minutes on days 1-3 of each cycle. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients with localized germinoma with normalization of markers who fail to achieve CR or PR who do not undergo second-look surgery undergo 3DRT or IMRT QD 5 days a week for 24 days. Patients undergo MRI and optional blood and tissue sample collection throughout the study. Patients may undergo LP for CSF sample collection during screening and follow up.

Group VI: Stratum II (carboplatin, etoposide, 3D-CRT, IMRT) Experimental Treatment 8 Interventions

Patients receive carboplatin IV over 15-60 minutes on day 1 and etoposide IV over 90-120 minutes on days 1-3 of each cycle. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients with localized germinoma achieving PR with normalization of markers who do not undergo second-look surgery undergo 3DRT or IMRT QD 5 days a week for 20 days. Patients undergo MRI and optional blood and tissue sample collection throughout the study. Patients may undergo LP for CSF sample collection during screening and follow up.

Group VII: Stratum I (carboplatin, etoposide, 3D-CRT, IMRT, surgery) Experimental Treatment 9 Interventions

See Detailed Description.

Who Is Running the Clinical Trial?

Children's Oncology Group

Lead Sponsor

Trials

467

Recruited

241,000+

Published Research Related to This Trial

Intensity-modulated radiotherapy (IMRT) provided a significantly better dose distribution to the tumor target area compared to three-dimensional conformal radiotherapy (3DCRT), with higher doses delivered to the gross tumor volume (GTV) and clinical target volume (CTV).

IMRT also demonstrated superior protection of normal tissues, as indicated by lower maximum and mean doses to critical structures like the pituitary gland and optic chiasm, suggesting it may enhance treatment safety while effectively targeting malignant gliomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dosimetric comparison of intensity-modulated radiotherapy and three-dimensional conformal radiotherapy for cerebral malignant gliomas. Zheng, R., Fan, R., Wen, H., et al.[2015]

In a study involving 20 patients with high-grade glioma, intensity-modulated radiation therapy (IMRT) provided better target coverage and reduced radiation exposure to critical normal tissues compared to three-dimensional conformal radiation therapy (3D-CRT).

IMRT significantly increased tumor control probability and decreased the risk of complications in normal tissues, suggesting it may enhance treatment outcomes while minimizing side effects for patients undergoing radiation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity modulated radiation therapy versus three-dimensional conformal radiation therapy for the treatment of high grade glioma: a dosimetric comparison. MacDonald, SM., Ahmad, S., Kachris, S., et al.[2022]

Intensity-modulated radiotherapy (IMRT) for high-grade gliomas improves target conformity and reduces radiation exposure to critical normal tissues compared to conventional three-dimensional conformal radiotherapy (3D-CRT), with significant dose reductions for structures like the optic nerves and brainstem.

IMRT achieves these benefits without increasing the total integral dose to nontarget tissues by more than 0.5%, resulting in an overall reduction of 7-10% in integral dose, which is crucial for minimizing potential side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity-modulated radiotherapy (IMRT) and conventional three-dimensional conformal radiotherapy for high-grade gliomas: does IMRT increase the integral dose to normal brain? Hermanto, U., Frija, EK., Lii, MJ., et al.[2022]

The study compared intensity-modulated radiotherapy (IMRT) using the Peacock system with stereotactically guided conformal radiotherapy (SCRT) in five patients with medium-sized convex-shaped brain tumors, finding that IMRT provided slightly better planning target volume (PTV) coverage.

While the doses to organs at risk (OAR) were higher with the Peacock method, all doses remained below clinically acceptable thresholds, indicating that IMRT can be a safe option for treating these tumors, though further improvements in planning methods may enhance outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of intensity-modulated tomotherapy with stereotactically guided conformal radiotherapy for brain tumors. Khoo, VS., Oldham, M., Adams, EJ., et al.[2019]

In a study of 97 early-stage breast cancer patients, intensity-modulated radiotherapy (IMRT) significantly improved dose delivery and homogeneity compared to three-dimensional conformal radiotherapy (3D-CRT), indicating better treatment precision.

IMRT also resulted in lower rates of acute and subacute skin toxicities, such as dermatitis and hyperpigmentation, suggesting it may be a safer option for patients, although both treatment methods were well tolerated overall.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prone hypofractionated whole-breast radiotherapy without a boost to the tumor bed: comparable toxicity of IMRT versus a 3D conformal technique. Hardee, ME., Raza, S., Becker, SJ., et al.[2018]

Intensity-modulated radiation therapy (IMRT) showed improved dose homogeneity and reduced mean doses to the cochlea compared to three-dimensional conformal radiation therapy (3DCRT) in children with medulloblastoma, based on a study of seven previously irradiated patients.

However, 3DCRT was more effective in sparing anterior cranial structures without compromising the dose to the posterior fossa, indicating that both techniques have unique advantages in treatment planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A dosimetric comparison between three-dimensional conformal radiation therapy and intensity-modulated radiation therapy in the treatment of posterior fossa boost in medulloblastoma. Gupta, M., Kant, R., Nautiyal, V., et al.[2018]

In a study of 54 patients with newly-diagnosed glioblastoma multiforme (GBM), intensity-modulated radiotherapy (IMRT) did not show a significant improvement in overall survival or progression-free survival compared to three-dimensional conformal radiotherapy (3D-CRT).

While IMRT allowed for better sparing of surrounding organs at risk, it did not result in lower toxicity levels compared to 3D-CRT, suggesting that the higher costs of IMRT may not be justified given the similar clinical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of intensity-modulated radiotherapy versus three-dimensional conformal radiotherapy on clinical outcomes in patients with glioblastoma multiforme. Chen, YD., Feng, J., Fang, T., et al.[2013]

Intensity modulated radiotherapy (IMRT) combined with three-dimensional brachytherapy (3D-BT) shows significant dosimetry advantages over three-dimensional conformal radiotherapy (3D-CRT), particularly in reducing radiation exposure to surrounding organs, while maintaining similar clinical efficacy in treating advanced cervical cancer.

IMRT significantly lowers the incidence of grade 1-2 acute toxicities in gastrointestinal, genitourinary, and hematologic systems compared to 3D-CRT, indicating a safer treatment option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical study of intensity modulated radiotherapy and three-dimensional conformal radiotherapy with three-dimensional brachytherapy and concurrent chemotherapy for patients with advanced cervical cancer]. Du, XX., Yang, H., Zhang, HJ., et al.[2018]

Between July 2005 and July 2007, 925 newly diagnosed cancer patients were treated with either 3D conformal radiation therapy (3D CRT) or intensity-modulated radiation therapy (IMRT) at King Chulalongkorn Memorial Hospital, with 3D CRT being the primary technique used in over 60% of cases.

IMRT was utilized in 35.9% of patients, particularly for nasopharyngeal, lung, and prostate cancers, indicating a targeted approach to treatment based on cancer type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A two-year experience of implementing 3 dimensional radiation therapy and intensity-modulated radiation therapy for 925 patients in King Chulalongkorn Memorial Hospital. Lertbutsayanukul, C., Shotelersuk, K., Khorprasert, C., et al.[2008]

In a study of 220 glioblastoma patients, intensity-modulated radiotherapy (IMRT) showed better target conformity and reduced acute neurological toxicities compared to three-dimensional conformal radiotherapy (3D-CRT).

Despite IMRT patients having worse pre-treatment neurological status, they experienced significantly fewer side effects like edema and concentration disorders, and had a median survival of 16.0 months compared to 13.4 months for 3D-CRT, although this difference in survival was not statistically significant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical and dosimetric study of radiotherapy for glioblastoma: three-dimensional conformal radiotherapy versus intensity-modulated radiotherapy. Thibouw, D., Truc, G., Bertaut, A., et al.[2019]

Intensity modulated radiation therapy (IMRT) has shown promising results in treating various tumors, including prostate, head and neck, and brain cancers, based on a retrospective review of 185 patients.

IMRT not only effectively targets tumors while minimizing damage to surrounding healthy tissues, but it also allows for dose escalation, which can improve tumor control and reduce treatment-related side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity modulated radiotherapy (IMRT) decreases treatment-related morbidity and potentially enhances tumor control. Teh, BS., Mai, WY., Grant, WH., et al.[2019]

In a study of 553 prostate cancer patients, intensity-modulated radiation therapy (IMRT) showed significantly better cancer control compared to three-dimensional conformal radiotherapy (3D-CRT) for intermediate- and high-risk patients, with higher rates of biochemical failure-free survival.

Both treatment methods had similar levels of genitourinary toxicity, but IMRT resulted in lower gastrointestinal toxicity compared to higher doses of 3D-CRT, indicating that IMRT can provide effective treatment without increasing side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparing morbidity and cancer control after 3D-conformal (70/74 Gy) and intensity modulated radiotherapy (78/82 Gy) for prostate cancer. Dolezel, M., Odrazka, K., Zouhar, M., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5722415/

Intensity modulated radiation therapy versus three ... As compared with 3D‐CRT, IMRT significantly increased the tumor control probability ( p ≤ 0.005 ) and lowered the normal‐tissue complication probability for ...

2. frontiersin.org frontiersin.org/journals/physics/articles/10.3389/fphy.2025.1632620/full

Three-dimensional conformal therapy vs. intensity ... Conclusion: IMRT provides significant dosimetric benefits and potentially lower toxicity compared to 3D-CRT in GBM treatment. While an exploratory analysis ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1053429601800576

Three-dimensional conformal radiation treatment planning ... This article will address the clinically relevant issues with regard to low- and intermediate-grade gliomas and the role of 3D-CRT planning. Specific issues ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06368817

NCT06368817 | A Study of Lower Radiotherapy Dose to ... This phase II trial studies how well lower dose radiotherapy after chemotherapy (Carboplatin & Etoposide) works in treating children with central nervous ...

5. ar.iiarjournals.org ar.iiarjournals.org/content/34/10/5715

Treatment Outcome of Radiation Therapy for Intracranial ... Results: Five-year recurrence-free survival (RFS) was 87% and overall survival was 97%. RT field was significantly associated with RFS, with 5-year RFS rates of ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10705506/

Comparison of the Effectiveness of Radiotherapy with 3D-CRT ... This study investigated the effectiveness of different modern radiotherapy strategies in the treatment of patients with newly diagnosed glioblastoma

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0360301609009390

Intensity-Modulated and 3D-Conformal Radiotherapy for ... Intensity-modulated radiotherapy was associated with the lowest irradiated volumes, with reductions of 7.5%, 12.2%, and 9.0% at dose levels of 20, 30, and 40 Gy ...

8. cureus.com cureus.com/articles/364616-assessment-and-comparison-of-3d-conformal-radiotherapy-with-volumetric-modulated-arc-therapy-for-preserving-remaining-brain-volume-in-high-grade-gliomas

Assessment and Comparison of 3D Conformal ... 3D-CRT is superior to 2D (two-dimensional) RT because it involves shaping radiation beams to match the contour of the tumor. The limitations of ...