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

Sponsor

Beijing Tiantan Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT05124951

Collaborator

(none)

150

Enrollment

Location

Arm

61.5

Anticipated Duration (Months)

2.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Intracranial Germ Cell CNS Tumor, Childhood	Radiation: Whole-ventricle irradiation Drug: Carboplatin/etoposide Drug: Ifosfamide/cisplatin/etoposide Procedure: Second-look surgery	Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

150 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Sep 15, 2021

Anticipated Primary Completion Date :

Oct 31, 2026

Anticipated Study Completion Date :

Oct 31, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: iGCTS 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 Whole-ventricle irradiation will be applied in patients with localized basal ganglia germ cell tumors after induction chemotherapy Drug: Carboplatin/etoposide Carboplatin/etoposide regimen is applied as induction chemotherapy in patients with basal ganglia germinoma Drug: Ifosfamide/cisplatin/etoposide Ifosfamide/cisplatin/etoposide regimen is applied as induction chemotherapy in patients with basal ganglia non-germinomatous germ cell tumors. Procedure: Second-look surgery Second-look surgery would be applied to patients who presented residue disease after induction chemotherapy.

Arm

Intervention/Treatment

Experimental: iGCTS

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

Whole-ventricle irradiation will be applied in patients with localized basal ganglia germ cell tumors after induction chemotherapy

Drug: Carboplatin/etoposide

Carboplatin/etoposide regimen is applied as induction chemotherapy in patients with basal ganglia germinoma

Drug: Ifosfamide/cisplatin/etoposide

Ifosfamide/cisplatin/etoposide regimen is applied as induction chemotherapy in patients with basal ganglia non-germinomatous germ cell tumors.

Procedure: Second-look surgery

Second-look surgery would be applied to patients who presented residue disease after induction chemotherapy.

Outcome Measures

Primary Outcome Measures

3-year event-free survival [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.]
Event-free survival (DFS) is calculated from the date of enrollment to the date of an event (relapse or death of any cause).
Change of score of the QoL questionnaire (PedsQL 4.0 : Pediatric Quality of Life Inventory Version 4.0 Generic Core Scales, Chinese edition) [Score will be obtained at baseline, 6 months posttreatment, yearly through 3 years posttreatment]
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)
Change of score of the QoL questionnaire (Short form-36) [Evaluation will be conducted at baseline, 6 months posttreatment, yearly through 3 years posttreatment]
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)
Change of score of Chinese Wechsler Intelligence Scale for Children [Score will be obtained at baseline, 6 months posttreatment, yearly through 3 years posttreatment]
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 .

Secondary Outcome Measures

3-year overall survival [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.]
Overall survival is determined from the date of diagnosis to the date of death of any cause or the last follow-up visit
Short-term adverse effects of treatments [From the beginning to the completion of chemoradiotherapy, approximately 6 months. Grade 3/4 toxicities will be documented]
NCI CTCAE 5.0 will be used for adverse effects evaluation

Eligibility Criteria

Criteria

Ages Eligible for Study:

3 Years to 30 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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