Title
A Phase 2 Trial of Chemotherapy followed by Response-Based Whole Ventricular & Spinal Canal Irradiation (WVSCI) for Patients with Localized Non-Germinomatous Central Nervous System Germ Cell Tumor

Description
This phase II trial studies the best approach to combine chemotherapy and radiation therapy (RT) based on the patient's response to induction chemotherapy in patients with non-germinomatous germ cell tumors (NGGCT) that have not spread to other parts of the brain or body (localized). This study has 2 goals: 1) optimizing radiation for patients who respond well to induction chemotherapy to diminish spinal cord relapses, 2) utilizing higher dose chemotherapy followed by conventional RT in patients who did not respond to induction chemotherapy. Chemotherapy drugs, such as carboplatin, etoposide, ifosfamide, and thiotepa, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy x-rays or high-energy protons to kill tumor cells and shrink tumors. Studies have shown that patients with newly-diagnosed localized NGGCT, whose disease responds well to chemotherapy before receiving radiation therapy, are more likely to be free of the disease for a longer time than are patients for whom the chemotherapy does not efficiently eliminate or reduce the size of the tumor. The purpose of this study is to see how well the tumors respond to induction chemotherapy to decide what treatment to give next. Some patients will be given RT to the spine and a portion of the brain. Others will be given high dose chemotherapy and a stem cell transplant before RT to the whole brain and spine. Giving treatment based on the response to induction chemotherapy may lower the side effects of radiation in some patients and adjust the therapy to a more efficient one for other patients with localized NGGCT.

Objective
PRIMARY OBJECTIVES:

I. To monitor outcome to ensure that children and young adults with localized central nervous system (CNS) non-germinomatous germ cell tumors (NGGCT) treated with induction chemotherapy followed by response evaluation and whole ventricular + spinal canal irradiation (WVSCI) will maintain the excellent 2-year progression free survival (PFS) rate as compared to ACNS0122 (NCT00047320).

II. To improve disease control by decreasing the number of spinal relapses for patients who achieve a complete response (CR) or partial response (PR) and receive WVSCI as compared to whole ventricular radiation on ACNS1123 (NCT01602666).

SECONDARY OBJECTIVES:

I. To estimate the response rates to induction chemotherapy and WVSCI for localized NGGCT patients who achieve a CR/PR.

II. To estimate the PFS and overall survival (OS) for localized NGGCT patients who achieve a CR/PR and receive WVSCI.

III. To estimate the PFS and OS for patients with less than a CR/PR following Induction who subsequently receive high-dose chemotherapy with peripheral stem cell rescue (HDCSCR).

IV. To estimate the response rate for patients with less than a CR/PR following Induction who subsequently receive HDCSCR.

EXPLORATORY OBJECTIVES:

I. To prospectively compare outcomes based on radiation modality, photon versus proton, including cognitive, social and behavioral functioning, auditory, and neuro-endocrine function.

II. To compare spinal column growth and cell counts following radiation as measured by height and weight, and complete blood count (CBC) values during and after radiation therapy, based on treatment modality (photon versus [vs.] proton therapy) and planned inclusion/exclusion of the vertebral body in patients < 13 years of age.

III. To compare local vs. central review recommendations for second-look surgery and document barriers for performing such surgeries as well as their clinical benefit in pediatric NGGCT.

IV. To prospectively evaluate and longitudinally model the cognitive, social, and behavioral functioning of children and young adults with localized CNS NGGCT with testing as per the Children's Oncology Group (COG) Standardized Neuropsychological and Behavioral Battery.

V. To evaluate patterns of disease recurrence/failure with respect to radiation dose distribution.

Treatment Experimental: Plan A (chemotherapy, WVSCI, second-look surgery if needed)
See Outline in Detailed Description.

Experimental: Plan B (chemotherapy, HDCSCR, second-look surgery if needed)
See Outline in Detailed Description.

Key Eligibility For full study eligibility, see this study's ClinicalTrials.gov record.

Applicable Disease Sites
Brain/Central Nervous System

Participating Institutions
Gundersen Health System; UW Health University Hospital