- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04474964
Focal Radiotherapy Plus Low Dose Craniospinal Irradiation Followed by Adjuvant Chemotherapy in WNT Medulloblastoma. (FOR-WNT2)
Focal Radiotherapy Plus Low Dose Craniospinal Irradiation Followed by Adjuvant Chemotherapy in WNT Subgroup Medulloblastoma.
Study Overview
Status
Conditions
Intervention / Treatment
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 (23.4-36Gy), 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 (23.4-36Gy), presence of significant late toxicities with such doses, but the increased risk of relapse with avoidance of CSI and/or local irradiation, the investigators hypothesize that further moderate reduction of CSI dose to 18Gy/10fx keeping the primary-site dose to 54Gy/30fx 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 (18Gy/10fx) plus tumor-bed boost (36Gy/20fx) for a total primary site dose of 54Gy/30fx without concurrent chemotherapy followed by standard 6-cycles of adjuvant systemic chemotherapy.
Study Type
Enrollment (Estimated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Tejpal Dr Gupta, MD
- Phone Number: (022) 2417 6015
- Email: tejpalgupta@rediffmail.com
Study Locations
-
-
Maharashtra
-
Mumbai, Maharashtra, India, 400012
- Recruiting
- Tata Memorial Hospital
-
Contact:
- Dr Tejpal Gupta, MD
- Phone Number: 6015 022-24177000
- Email: tejpalgupta@rediffmail.com
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Age more than 3 years and less than 16 years.
- Newly diagnosed WNT pathway medulloblastoma.
- Post-surgery residual disease less than 1.5 cm2 on post-operative MRI brain.
- No evidence of metastatic disease in the brain, spine or cerebral spinal fluid (CSF) assessed by MRI of the brain/spine and lumbar puncture for CSF cytology.
- Fit for initiation of adjuvant treatment within 6-weeks of surgery
Exclusion Criteria:
- Age Less than 3 and more than 16 years.
- Molecular subgroup other than WNT pathway.
- Post-surgery residual disease more than 1.5cm2 on post-operative imaging.
- Evidence of any metastatic disease in the brain, spine or CSF.
- Previous history of radiotherapy or chemotherapy prior to study enrollment.
- Not fit for initiation of adjuvant treatment within 6 weeks of surgery.
- Not willing for consent/assent.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Low Dose Craniospinal Irradiation
WNT subgroup medulloblastoma patients accrued in the study will be treated with Low-dose Craniospinal Irradiation (18Gy/10fx) plus focal conformal tumor-bed boost (36Gy/20fx) for total primary-site dose of 54Gy/30fx over 6-weeks.
Followed by adjuvant multi-agent systemic chemotherapy which will be initiated 4-6 weeks after completion of radiotherapy provided the ANC >1500 and platelet count >1,00,000.
A total of 6 cycles of alternating chemotherapy every 4-weekly will be planned as per our standard practice using CET protocol.
|
The intervention arm of the study is to prospectively evaluate disease-related outcomes of low-dose CSI plus focal radiotherapy without concurrent chemotherapy followed by standard 6-cycles of adjuvant systemic chemotherapy in WNT-pathway medulloblastoma.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Relapse-free survival will be analysed using using the product-limit method of Kaplan-Meier and compared using the log-rank test.
Time Frame: 5 years
|
Measure Relapse-free survival in WNT medulloblastoma treated with low-dose CSI plus focal radiotherapy without concurrent chemotherapy followed by standard 6-cycles of adjuvant systemic chemotherapy.
Relapse free survival will be calculated from the date of surgery till the first documented clinico-radiological evidence of relapse (recurrence/progression).
|
5 years
|
Overall Survival of Participants will be analysed using the product-limit method of Kaplan-Meier and compared using the log-rank test.
Time Frame: 5 years
|
Measure Overall survival in WNT medulloblastoma treated with low-dose CSI plus focal radiotherapy without concurrent chemotherapy followed by standard 6-cycles of adjuvant systemic chemotherapy.Overall survival will be measured from the date of diagnosis till death from any cause.
|
5 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Neuro-cognitive function of Participants will be analysed longitudinally over time using linear regression model with time-test for trend
Time Frame: 5 years
|
Neurocognitive Outcome will be assessed using Wechsler scale for children by comparing pre-radiotherapy result with assessment done 3-6 months after radiotherapy, at 1-year post-treatment, and annually thereafter till 5-years.
|
5 years
|
Growth Hormone levels of Participants will be analysed longitudinally over time using linear regression model with time-test for trend.
Time Frame: 5 years
|
Serial Serum growth hormone(ng/ml) levels will be done by comparing pre-radiotherapy levels with biochemical assessment done 3-6 months after radiotherapy, at 1-year post-treatment and annually thereafter for 5-years.
|
5 years
|
Thyroid function levels of Participants will be analysed longitudinally over time using linear regression model with time-test for trend.
Time Frame: 5 years
|
Serial Thyroid function levels : TSH , T3, T4 levels will be done by comparing pre-radiotherapy levels with biochemical assessment done 3-6 months after radiotherapy, at 1-year post-treatment and annually thereafter for 5-years.
|
5 years
|
Cortisol levels of Participants will be analysed longitudinally over time using linear regression model with time-test for trend.
Time Frame: 5 years
|
Serial Cortisol levels (mcg/dl) will be done by comparing pre-radiotherapy levels with biochemical assessment done 3-6 months after radiotherapy, at 1-year post-treatment and annually thereafter for 5-years.
|
5 years
|
Sex Hormone levels of Participants will be analysed longitudinally over time using linear regression model with time-test for trend.
Time Frame: 5 years
|
Sex Hormone levels will be done by comparing pre-radiotherapy levels with biochemical assessment done 3-6 months after radiotherapy, at 1-year post-treatment and annually thereafter for 5-years.
|
5 years
|
Pure tone Audiometry of Participants will be analysed longitudinally over time using linear regression model with time-test for trend.
Time Frame: 5 years
|
Hearing assessment will be done by comparing baseline results with hearing assessment 3-6 months after radiotherapy, at 1-year post-treatment, and annually thereafter for 5-years.
|
5 years
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 3468
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Medulloblastoma, WNT-activated
-
St. Jude Children's Research HospitalEli Lilly and CompanyActive, not recruitingBrain Cancer | Brain Tumor | Medulloblastoma | Brain Tumor, Recurrent | CNS Tumor | Medulloblastoma Recurrent | CNS Cancer | Medulloblastoma, Non-WNT/Non-SHH | Brain Tumor, Pediatric | CNS Neoplasm | Brain Tumor, Refractory | Medulloblastoma, Non-WNT/Non-SHH, Group 3 | Medulloblastoma, Non-WNT/Non-SHH, Group 4United States
-
St. Jude Children's Research HospitalNovartis PharmaceuticalsActive, not recruitingGlioma | Neoplasms | Glioblastoma | Neoplasms, Neuroepithelial | Central Nervous System Neoplasms | Brain Cancer | Brain Tumor | Ependymoma | Medulloblastoma | Anaplastic Astrocytoma | Anaplastic Ganglioglioma | Anaplastic Ependymoma | Anaplastic Oligodendroglioma | Pineoblastoma | Recurrent Medulloblastoma | CNS Tumor | Pediatric... and other conditionsUnited States
-
Oslo University HospitalUnknownSubclinical Sleep-Activated Epileptiform Activity | CSWSNorway
-
Novartis PharmaceuticalsCompletedPI3K Pathway Activated TumorsUnited States
-
Novartis PharmaceuticalsTerminatedPTCH1 or SMO Activated Solid and Hematologic TumorsUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)Active, not recruitingUntreated Childhood MedulloblastomaUnited States, Canada, Australia, New Zealand, Switzerland, Netherlands
-
University Hospital, Strasbourg, FranceRecruitingResistance to Activated Protein C in the Determination of Protein S ActivityFrance
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)CompletedRecurrent Childhood Medulloblastoma | Recurrent Ependymoma | Recurrent MedulloblastomaUnited States
-
University of California, San FranciscoWashington University School of Medicine; University of Washington; Pacific Pediatric... and other collaboratorsRecruitingMedulloblastoma | Medulloblastoma, Childhood | Medulloblastoma RecurrentUnited States
-
Taichung Veterans General HospitalRecruitingCardiopulmonary Bypass | Heparin | Surgery, Cardiac | Tranxemic Acid | Activated Clotting TimeTaiwan
Clinical Trials on Low dose Craniospinal Irradiation plus Focal Radiotherapy
-
British Columbia Cancer AgencyUnknown
-
Cancer Institute and Hospital, Chinese Academy...Shanxi Province Cancer Hospital; Beijing Tongren Hospital; Fujian Medical University...Recruiting
-
Sichuan Cancer Hospital and Research InstituteRecruitingLocally Advanced Nasopharyngeal CarcinomaChina
-
Lancashire Teaching Hospitals NHS Foundation TrustNIHR Lancashire Clinical Research FacilityCompleted
-
Juravinski Cancer CenterMitacs; McMaster University; Northern Ontario School of MedicineCompleted
-
Philippe MeyerRecruitingAmyloid CardiomyopathySwitzerland
-
Thomas ZilliRecruitingAlzheimer DiseaseSwitzerland
-
Sichuan Cancer Hospital and Research InstituteNot yet recruiting
-
Kyung Hee University Hospital at GangdongSMG-SNU Boramae Medical Center; Chungbuk National University Hospital; Korea...RecruitingAlzheimer DiseaseKorea, Republic of
-
University of Erlangen-Nürnberg Medical SchoolJohann Wolfgang Goethe University HospitalRecruitingOsteoarthritis | ArthrosisGermany