Lower Radiotherapy Dose for Brain Tumors

Recruiting at 55 trial locations

Age: < 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Children's Oncology Group

Disqualifiers: Pregnancy, Breastfeeding, Prior tumor therapy, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This phase II trial studies how well lower dose radiotherapy after chemotherapy (Carboplatin \& Etoposide) works in treating children with central nervous system (CNS) germinomas. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of tumor cells. Etoposide is in a class of medications known as podophyllotoxin derivatives. It blocks a certain enzyme needed for cell division and DNA repair and may kill cancer cells. Researchers want to see if lowering the dose of standard radiotherapy (RT) after chemotherapy can help get rid of CNS germinomas with fewer long-term side effects.

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.

What data supports the effectiveness of the treatment for brain tumors?

Research comparing 3D-CRT and IMRT for brain tumors like medulloblastoma and glioblastoma shows that both treatments effectively target the tumor while minimizing damage to surrounding healthy tissues. This suggests that these therapies can be effective in treating brain tumors by focusing radiation precisely where it's needed. ^{1 2 3 4 5}

Is lower radiotherapy dose for brain tumors safe for humans?

Research shows that both three-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT) are generally safe for humans, with IMRT often resulting in fewer side effects like gastrointestinal and genitourinary issues compared to 3D-CRT. ^{2 6 7 8 9}

How does the lower radiotherapy dose treatment for brain tumors differ from other treatments?

This treatment uses a lower dose of radiation, potentially reducing side effects while still effectively targeting brain tumors. It may involve techniques like intensity-modulated radiation therapy (IMRT), which precisely targets the tumor and spares surrounding healthy tissue, offering a more tailored approach compared to traditional methods. ^{1 6 10 11 12}

Research Team

Mohamed S Abdelbaki

Principal Investigator

Children's Oncology Group

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

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

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.

Participant Groups

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+

Findings from Research

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 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]

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 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) 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]

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]

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 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]

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]

References

1. India 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. [2018]

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

Clinical and dosimetric study of radiotherapy for glioblastoma: three-dimensional conformal radiotherapy versus intensity-modulated radiotherapy. [2019]

3. Thailand 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. [2008]

4. China pubmed.ncbi.nlm.nih.gov

Effect of intensity-modulated radiotherapy versus three-dimensional conformal radiotherapy on clinical outcomes in patients with glioblastoma multiforme. [2013]

5. Cyprus pubmed.ncbi.nlm.nih.gov

Dosimetric comparison of intensity-modulated radiotherapy and three-dimensional conformal radiotherapy for cerebral malignant gliomas. [2015]

6. England pubmed.ncbi.nlm.nih.gov

Intensity modulated radiotherapy (IMRT) decreases treatment-related morbidity and potentially enhances tumor control. [2019]

7. Germany 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. [2022]

8. United States 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. [2018]

9. China 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]. [2018]

10. United States 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. [2022]

11. United States 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? [2022]

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

Comparison of intensity-modulated tomotherapy with stereotactically guided conformal radiotherapy for brain tumors. [2019]