Ignite Creation Date:
2024-05-06 @ 2:57 PM
Last Modification Date:
2024-10-26 @ 1:40 PM
Study NCT ID:
NCT04474964
Status:
RECRUITING
Last Update Posted:
2024-01-18
First Post:
2020-07-14
Brief Title:
Focal Radiotherapy Plus Low Dose Craniospinal Irradiation Followed by Adjuvant Chemotherapy in WNT Medulloblastoma
Sponsor:
Tata Memorial Centre
Organization:
Tata Memorial Centre
Study Overview
Official Title:
Focal Radiotherapy Plus Low Dose Craniospinal Irradiation Followed by Adjuvant Chemotherapy in WNT Subgroup Medulloblastoma
Status:
RECRUITING
Status Verified Date:
2024-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
FOR-WNT2
Brief Summary:
This clinical study is going to be done on a type of brain tumor in children called Medulloblastoma The WNT pathway type of medulloblastoma is considered to be low risk and have the best outcomes in terms of survival With the current standard of care for this type of medulloblastoma it is believed by the investigators that we are over treating the disease and increasing the long term side effects of these children Several groups in the world are testing de-intensification of treatment in this favourable subset of children who experience long term late side effects of therapy By reducing the dose to the craniospinal axis and keeping the total tumor bed dose the same in this study the investigators are expecting to reduce some of the late side effects of craniospinal irradiation without compromising disease control and survival
Detailed Description:
WNT pathway medulloblastomas have the best prognosis amongst all four subgroups with 5-year overall survival exceeding 90 Overall medulloblastoma is more common in males They can occur at all ages but are uncommon in infants They are mostly uniform in their genetic aberrations histological pattern and clinical presentation The WNT pathway is involved in regulating embryonal development in the brain They are frequently described as having CTNNB1 mutations nuclear immunohistochemical staining for β-catenin and monosomy six deletion of one copy of chromosome 6 in the tumor Thus monosomy 6 in conjunction with nuclear β-catenin accumulation is considered a sensitive and specific marker for WNT pathway medulloblastoma they are typically located in the midline vermian region filling up the fourth ventricle and infiltrating the brain stem consistent with their proposed cell of origin from the dorsal brainstem nuclei The immediate impact of enhanced understanding of molecular biology has led to biologically driven next-generation clinical trials in newly diagnosed medulloblastoma Given the excellent long-term survival outcomes in WNT-pathway medulloblastoma and potential for significant late toxicities with currently prevalent doses of CSI 234-36Gy it has been hypothesized that further reduction of dose or in certain cases avoidance of CSI would translate into reduction in late morbidity of treatment
In our first generation FOR-WNT study the investigators had avoided upfront CSI and treated the tumor-bed alone with focal conformal radiotherapy in low-risk WNT-pathway medulloblastoma followed by 6-cycles of adjuvant systemic chemotherapy However early experience from our own study and similar results from another study primary chemotherapy approach completely avoiding radiotherapy suggests an unduly increased risk of relapse - spinal leptomeningeal or supratentorial if CSI is avoided and local recurrence at primary site too if radiation is completely avoided Given the excellent long-term survival outcomes in WNT-pathway medulloblastoma treated with currently prevalent doses of CSI 234-36Gy presence of significant late toxicities with such doses but the increased risk of relapse with avoidance of CSI andor local irradiation the investigators hypothesize that further moderate reduction of CSI dose to 18Gy10fx keeping the primary-site dose to 54Gy30fx would translate into a meaningful reduction in late morbidity of treatment without compromising disease control or survival Thus the investigators herewith propose the second-generation study FOR-WNT 2 to include low-dose CSI 18Gy10fx plus tumor-bed boost 36Gy20fx for a total primary site dose of 54Gy30fx without concurrent chemotherapy followed by standard 6-cycles of adjuvant systemic chemotherapy
In our first generation FOR-WNT study the investigators had avoided upfront CSI and treated the tumor-bed alone with focal conformal radiotherapy in low-risk WNT-pathway medulloblastoma followed by 6-cycles of adjuvant systemic chemotherapy However early experience from our own study and similar results from another study primary chemotherapy approach completely avoiding radiotherapy suggests an unduly increased risk of relapse - spinal leptomeningeal or supratentorial if CSI is avoided and local recurrence at primary site too if radiation is completely avoided Given the excellent long-term survival outcomes in WNT-pathway medulloblastoma treated with currently prevalent doses of CSI 234-36Gy presence of significant late toxicities with such doses but the increased risk of relapse with avoidance of CSI andor local irradiation the investigators hypothesize that further moderate reduction of CSI dose to 18Gy10fx keeping the primary-site dose to 54Gy30fx would translate into a meaningful reduction in late morbidity of treatment without compromising disease control or survival Thus the investigators herewith propose the second-generation study FOR-WNT 2 to include low-dose CSI 18Gy10fx plus tumor-bed boost 36Gy20fx for a total primary site dose of 54Gy30fx without concurrent chemotherapy followed by standard 6-cycles of adjuvant systemic chemotherapy
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None