JCCG CNSGCT2021: A Randomized Controlled Clinical Study in Patients with Central Nervous System Germ Cell Tumor

JRCT ID: jRCTs051220066

Registered date:22/07/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Central Nervous System Germ Cell Tumor
• Date of first enrollment: 20/10/2022
• Target sample size: 380
• Study type: Interventional

Intervention(s)

Germinoma stratum
Arm A1:
1)Chemotherapy: 4 cycles alternating CE regimen (carboplatin 560 mg/m2 day1, etoposide 150 mg/m2 day1-3) and PE regimen (cisplatin 90 mg/m2 day1, etoposide 150 mg/m2 day1-3).
2) Radiotherapy: whole brain or whole ventricular radiation according tumor location (1.8 Gy/day, 5 days/week, 13 times and 23.4 Gy in total) is introduced between first and second cycle start of chemotherapy.
3) Tumor removal: if the residual tumor is identified after chemotherapy and radiotherapy and can be removed safely, tumor removal is performed.

Arm B1:
1) Chemotherapy: 4 cycles alternating CE regimen and PE regimen.
2) Radiotherapy: whole brain or whole ventricular radiation therapy according tumor location (1.8 Gy/day, 5 days/week, 10 times and 18 Gy in total) is introduced between first and second cycle start of chemotherapy.
3) Tumor removal: if the residual tumor is identified after chemotherapy and radiotherapy and can be removed safely, tumor removal is performed.

Malignant germ cell tumor stratum
Arm A2:
1) Chemotherapy: 5 cycles of PEC regimen (cisplatin 90 mg/m2 day1, etoposide 150 mg/m2 day1-3, cyclophosphamide 1g/m2 day1, 2).
2) Radiotherapy: craniospinal irradiation (1.8 Gy/day, 5 days/week, 13 times and 23.4 Gy in total) followed by local radiation therapy (1.8 Gy/day, 5 days/week, 17 times and 30.6 Gy in total) is introduced after chemotherapy.
3) Tumor removal: if a residual tumor is identified after chemotherapy and radiotherapy and can be removed safely, tumor removal is performed.

Arm B2:
1) Chemotherapy: 5 cycles of PEC regimen.
2) Radiotherapy: local radiation therapy (1.8 Gy/day, 5 days/week, 30 times and 54 Gy in total) is introduced after chemotherapy.
3) Tumor removal: if the residual tumor is identified after chemotherapy and radiotherapy and can be removed safely, tumor removal is performed.
4) High dose chemotherapy (HDC): HDC (thiotepa 200 mg/ m2 day-12, -11, -5, -4, melphalan 70 mg/ m2 day-11, -5, -4, peripheral blood stem cell transplantation day 0) is performed in the residual tumor after chemotherapy, radiotherapy and tumor removal, viable malignant tumor component identified in the removed tumor.

Outcome(s)

• Primary Outcome: 5-year progression free survival rate (5-year PFS)

Secondary Outcome

5-year overall survival rate (5 year OS)
Overall response rate (CR+PR rate)
Proportion of 5-year Quality of Life (QOL) preservation
Proportion of 5-year cognitive funcition preservation
Proportion of adverse events

Key inclusion & exclusion criteria

• Age minimum: Not applicable
• Age maximum: Not applicable
• Gender: Both

Include criteria

Registration criteria
1) Diagnosed as newly diagnosed central nervous system germ cell tumor in pathological diagnosis, or clinically proven diagnosis of central nervous system germ cell tumor.
2) Registered in the observational study for pediatric solid tumors by Japan Children's Oncology Group (JCCG).
3) Any age
4) No prior chemotherapy or head radiation therapy for any intracranial tumors.
5) Written informed consent is obtained from the patient or his/her legal guardian.

Germinoma stratum
1) Diagnosed as germinoma in pathological diagnosis.
2) 3 years or older, less than 30 years.
3) Serum alpha-fetoprotein (AFP)<10 ng/mL and human chorionic gonadotropin (HCG)<200mIU/ml.
4) No spinal dissemination.
5) Protocol treatment can be started within 6 weeks after surgery .
6) ECOG performance status (PS) of 0, 1, 2, or 3 due to neurological signs caused by the tumor.
7) The following conditions are met within 14 days prior to registration.
1. WBC>=2000/microliter and neutrophil >=1000/microliter
2. PLT>=100,000/microliter
3. AST<=100IU/L
4. D-Bil<=1.0mg/dl
5. Serum creatinine level is below the upper limit of normal value

Malignant germ cell tumor stratum
1) Diagnosed as malignant germ cell tumor (yalk sac tumor, embryonal carcinoma, choriocarcinoma) in pathological diagnosis or mixed with malignant germ cell tumor or clinically diagnosed as malignant germ cell tumor with serum AFP>=250 ng/mL or HCG >=500mIU/ml.
2) 3 years or older, less than 30 years.
3) No multiple tumors.
4) No dissemination.
5) Protocol treatment can be started within 6 weeks after surgery or cllinial diagnosis.
6) ECOG performance status (PS) of 0, 1, 2, or 3 due to neurological signs caused by the tumor.
7) The following conditions are met within 14 days prior to registration
1. WBC>=2000/microliter and neutrophil >=1000/microliter
2. PLT>=100,000/microliter
3. AST<=100IU/L
4. D-Bil<=1.0mg/dl
5. Serum creatinine level is below the upper limit of normal value

Prospective observation stratum
1) Diagnosed pathologically or clinically diagnosed as germ cell tumor except for germinoma stratum and malignant germ cell tumor stratum
2) At any age
3) Regardless of tumor location, number, and dissemination

Exclude criteria

Germinoma stratum and malignant germ cell tumor stratum
1) Active double cancer (synchronous double cancer and metachronous double cancer with disease-free period of 5 years or less).
2) Complicated with extracranial metastasis.
3) Complicated heart disease requiring treatment.
4) Pregnant or nursing.

Prospective observation stratum
1) Judgement of inappropriate inclusion by physician

Related Information

• Primary Sponsor: ARAKAWA Yoshiki
• Source(s) of Monetary Support: Japan Agency for Medical Research and Development