Chemotherapy Followed by Response-Based Reduced Radiation Therapy for Patients With Central Nervous System Germinomas

Childhood Central Nervous System Germinoma Clinical Trial

Official title: A Phase II Trial Evaluating Chemotherapy Followed by Response-Based Reduced Radiation Therapy for Patients With Central Nervous System Germinomas

Status Not yet recruiting

Clinical Trial Summary

A phase II trial that is attempting to build upon the excellent results of ACNS1123 stratum 2 by reducing the Radiotherapy (RT) dose for patients in a Complete Response (CR) after chemotherapy. The trial will be testing a further reduction in the whole ventricular irradiation (WVI) dose. Additionally, patients with metastatic disease and basal ganglia and thalamic germinoma will be included, and they will be treated with craniospinal irradiation (CSI) or whole brain irradiation (WBI) respectively.

Clinical Trial Description

PRIMARY OBJECTIVES I. To determine whether 12 Gy whole ventricular irradiation (WVI) and 12 Gy tumor boost would maintain similar efficacy compared to ACNS1123 stratum 2 as measured by event-free survival (EFS) in eligible patients with localized primary central nervous system (CNS) germinoma who present with serum and/or CSF human chorionic gonadotropin-beta (hCGβ) ≤ 100 IU/L and normal AFP, and meet complete response (CR) or continued complete response (CCR) criteria following chemotherapy/second-look surgery (Stratum 1). SECONDARY OBJECTIVES I. To estimate the EFS distribution for patients with localized midline - including bifocal - CNS germinoma with partial response (PR) after chemotherapy, followed by 18 Gy WVI and 12 Gy tumor boost (Stratum 2). II. To estimate the EFS distribution for patients with localized midline - including bifocal - CNS germinoma with less than a PR after chemotherapy, followed by 24 Gy WVI and 12 Gy tumor boost (Stratum 3). III. To estimate the overall survival (OS), response rates to chemotherapy and radiotherapy (RT), as well as the patterns of failure of the various cohorts based on tumor characteristics, treatment regimen, and treatment modality. IV. To determine the impact of tumor characteristics, treatment regimen and treatment modalities on the long-term neuroendocrine function for patients with CNS germinomas. V. To prospectively evaluate processing speed of children and young adults with CNS germinoma through the Children's Oncology Group (COG) Standardized assessment battery. EXPLORATORY OBJECTIVES: I. To estimate the EFS distribution for patients with metastatic germinomas treated with chemotherapy followed by craniospinal irradiation (CSI) [18 Gy for CR/CCR (Stratum 4)] or [24 Gy for less than CR (Stratum 5)] with a 12 Gy tumor boost to the pre-treatment volume, including metastatic sites. II. To estimate the EFS distribution for patients with basal ganglia and thalamic germinomas (BGTG) treated with chemotherapy followed by whole brain irradiation (WBI) [18 Gy for CR/CCR (Stratum 6)] or [24 Gy for less than CR (Stratum 7)] with a 12 Gy tumor boost to the pre-treatment volume. III. To prospectively collect blood, cerebrospinal fluid, and tumor tissue at diagnosis and second-look surgery (if feasible) for future biology studies. IV. To prospectively measure the incidence of cerebral vascular events (stroke or transient ischemic attacks) in the follow-up period and longitudinally evaluate and model the cognitive, social and behavioral functioning of children and young adults with CNS germinoma through the COG Standardized assessment battery, and compare these outcomes based on tumor characteristics, treatment regimen, and treatment modality. OUTLINE: All patients diagnosed with germinoma will receive Induction Chemotherapy, which includes four cycles of CARBOplatin and Etoposide followed by response evaluation (imaging and tumor markers). Based on rapid central review of tumor response assessment at end of Induction (end of Cycle 4), patients will proceed to second-look surgery or treatment with RT Induction Chemotherapy (All Patients) All patients will receive 4 cycles of Induction chemotherapy consisting of CARBOplatin/Etoposide. Each cycle lasts 21 days. STRATUM 1 (12 Gy WVI + 12 Gy boost) STRATUM 2 (18 Gy WVI + 12 Gy boost) STRATUM 3 (24 Gy WVI + 12 Gy boost) STRATUM 4 (18 Gy CSI + 12 Gy boost) STRATUM 5 (24 Gy CSI + 12 Gy boost) STRATUM 6 (18 Gy WBI + 12 Gy boost) STRATUM 7 (24 Gy WBI + 12 Gy boost) ;

Related Conditions & MeSH terms

• Childhood Central Nervous System Germinoma
• Germinoma
• Intracranial Germ Cell Tumor
• Neoplasms, Germ Cell and Embryonal

• NCT number: NCT06368817
• Study type: Interventional
• Source: Children's Oncology Group
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: May 4, 2024
• Completion date: November 4, 2033