The Efficacy of WVI in Patients With Localized Basal Ganglia Intracranial Germ Cell Tumors

Study Overview
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Brief Summary
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Primary endpoint three-year disease-free survival of patients with localized basal ganglia germ cell tumors receiving whole-ventricle irradiation Health-related quality of life measured by PedsQL 4.0 and SF-36 Second endpoint three-year overall survival of patients with localized basal ganglia germ cell tumors receiving whole-ventricle irradiation Adverse effects of chemoradiotherapy measured by NCI CTCAE 5.0

Detailed Description
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Intracranial germ cell tumors originating from the basal ganglia area are rare, accounting for less than 20% of patients. Radiotherapy played a vital role in the treatment of this malignancy. However, the optimal target volume is still undetermined. Our study regarding relapse patterns of different radiation volumes showed that the ventricular system and ipsilateral frontal lobe were at risk of relapse after focal radiotherapy. Although craniospinal irradiation (CSI) and whole-brain irradiation (WBI) could significantly reduce the relapse in the above areas, the adverse effect on the quality of life is still a concern. As a result, the investigators proposed whole-ventricular irradiation (WVI) in patients with localized basal ganglia germ cell tumors. In order to evaluate its efficacy and safety, the investigators designed this phase II study.

Official Title
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The Efficacy of Whole-ventricle Irradiation Plus Primary Boost in Patients With Localized Basal Ganglia Germ Cell Tumors: Prospective Phase II Study

Conditions
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Intracranial Germ Cell CNS Tumor, Childhood

Intervention / Treatment
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* Radiation: Whole-ventricle irradiation
* Drug: Carboplatin/etoposide
* Drug: Ifosfamide/cisplatin/etoposide
* Procedure: Second-look surgery


Participation Criteria
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Eligibility Criteria
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Stratum I: germinoma Inclusion Criteria: 3 years ≤ age ≤ 30 years Newly diagnosed Unilateral basal ganglia/thalamus lesion Germinoma：Histologically confirmed; and/or serum and/or CSF beta-HCG elevation (≤50IU/L); AFP negative No radiological evidence of additional lesions in the CNS Negative CSF cytology test Adequate organ function Written informed consent Exclusion Criteria: Bilateral basal ganglia/ thalamus lesions Synchronous pineal or sellar/suprasellar lesion Diabetes insipidus With extracranial lesion(s) Serum/CSF β-HCG >50IU/L without histology Mature teratoma with normal tumor markers Inadequate organ function Poor compliance Stratum II: non-germinomatous germ cell tumors Inclusion Criteria: 3 years ≤ age ≤ 30 years Newly diagnosed Unilateral basal ganglia/thalamus lesion NGGCTs: Histologically confirmed; and/or serum and/or CSF AFP elevation; beta-HCG≥500IU/L No radiological evidence of additional lesions in the CNS Negative CSF cytology test Adequate organ function Written informed consent Exclusion Criteria: Bilateral basal ganglia/ thalamus lesions Synchronous pineal or sellar/suprasellar lesion Diabetes insipitus With extracranial lesion(s) 50IU/L<serum/CSF β-HCG <500IU/L without histology Mature teratoma with normal AFP and β-HCG <500IU/L Inadequate organ function Poor compliance

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: iGCTS<br>Stratum I (Germinoma) Patients who achieved complete response after induction chemotherapy will receive WVI 2400cGy/15f plus primary boost 640cGy/4f. Stratum II (NGGCTs) At the time of response evaluation before radiotherapy, those with complete response or residue disease <1.5cm will receive WVI 3060cGy/17f plus primary boost 2340cGy/13f. | Radiation: Whole-ventricle irradiation<br>* Whole-ventricle irradiation will be applied in patients with localized basal ganglia germ cell tumors after induction chemotherapy<br>Drug: Carboplatin/etoposide<br>* Carboplatin/etoposide regimen is applied as induction chemotherapy in patients with basal ganglia germinoma<br>Drug: Ifosfamide/cisplatin/etoposide<br>* Ifosfamide/cisplatin/etoposide regimen is applied as induction chemotherapy in patients with basal ganglia non-germinomatous germ cell tumors.<br>Procedure: Second-look surgery<br>* Second-look surgery would be applied to patients who presented residue disease after induction chemotherapy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 3-year event-free survival | Event-free survival (DFS) is calculated from the date of enrollment to the date of an event (relapse or death of any cause). | From the enrollment to the event (relapse or death of any cause), approximately 3 years. The patients will receive long-term follow-up including MRI and serum tumor markers examination every 3 months until 36 months. | 
| Change of score of the QoL questionnaire (PedsQL 4.0 : Pediatric Quality of Life Inventory Version 4.0 Generic Core Scales, Chinese edition) | The PedsQL 4.0 Generic Core Scale contains 23 items that measures physical (eight items), emotional (five items), social (five items), and school (five items) functions. The Scale comprises parallel patient self-report and parent proxy-report formats. The items are reverse-scored and trans- formed to a 0-100 scale according to the instructions, and higher scores indicate a better HRQOL. (age ≤18 years) | Score will be obtained at baseline, 6 months posttreatment, yearly through 3 years posttreatment | 
| Change of score of the QoL questionnaire (Short form-36) | Altogether, 36 questions with standardized response choices were organized into eight scales, including physical functioning (PF), role limitations as a result of physical health problems (RP), body pain (BP), general health perceptions (GH), vitality (VT), social functioning (SF), role limitations as a result of emotional problems (RE), and general mental health (MH). Additionally, reported health transition (HT) was used to evaluate general health changes during the previous year. The raw scores were converted to a 0-100 scale according to the instructions, and higher scores indicated a better HRQOL. Physical component score (PCS) and mental component score (MCS) were also calculated. (Age >15 years) | Evaluation will be conducted at baseline, 6 months posttreatment, yearly through 3 years posttreatment | 
| Change of score of Chinese Wechsler Intelligence Scale for Children | The intelligence of the child was tested by the China-Wechsler Intelligence Scale for Children (C-WISC), which was revised by Gong and Cai at Hunan Medical University. The C-WISC consists of 11 individual tests that include six verbal tests [Information (I), Comprehend (C), Sorting (S), Arithmetic (A), Vocabulary (V), and Digit symbol (D)] and five performance tests [Picture Completing (PC), Picture Arrangement (PA), Block Pattern (BP), Object Assembly (OA), and Coding (CD)]. Based on individual testing, vocabulary scores (V), procedure scores (P), and full scores (F) were obtained. Furthermore, the VIQ, PIQ, and full intelligence quotient (FIQ) were calculated progressively . | Score will be obtained at baseline, 6 months posttreatment, yearly through 3 years posttreatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 3-year overall survival | Overall survival is determined from the date of diagnosis to the date of death of any cause or the last follow-up visit | From the enrollment to the death of any cause or last follow-up, approximately 3 years.The patients will receive long-term follow-up including MRI and serum tumor markers examination every 3 months until 36 months. | 
| Short-term adverse effects of treatments | NCI CTCAE 5.0 will be used for adverse effects evaluation | From the beginning to the completion of chemoradiotherapy, approximately 6 months. Grade 3/4 toxicities will be documented | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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intracranial germ cell tumors, basal ganglia, radiotherapy, target volume, quality of life