A Study of a New Way to Treat Children and Young Adults with a Brain Tumor Called NGGCT

Active:	Yes
Cancer Type:	Germ Cell Tumor Gestational trophoblastic disease Testicular Cancer Unknown Primary	NCT ID:	NCT04684368
Trial Phases:	Phase II	Protocol IDs:	ACNS2021 (primary) ACNS2021 NCI-2020-13175
Eligibility:	3 - 29 Years, Male and Female	Study Type:	Treatment
Study Sponsor:	Children's Oncology Group
NCI Full Details:	http://clinicaltrials.gov/show/NCT04684368

Summary

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.

Objectives

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.

OUTLINE:

INDUCTION CHEMOTHERAPY: Patients receive carboplatin intravenously (IV) over 15-60 minutes on day 1 and etoposide IV over 90-120 minutes on days 1-3 of cycles 1, 3, and 5. Patients also receive ifosfamide IV over 60 minutes and etoposide IV over 60-120 minutes on days 1-5 of cycles 2, 4, and 6. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

Patients are assigned to 1 of 2 plans (ventricular + spinal canal irradiation [WVSCI] or high-dose chemotherapy with peripheral stem cell rescue [HDCSCR]) based on response to induction chemotherapy:

* Patients who achieve radiographic CR/PR with marker normalization proceed to WVSCI. Patients who achieve radiographic CR without marker normalization proceed to HDCSCR.

* Patients who achieve less than radiographic CR/PR with marker normalization proceed to second-look surgery (unless contraindicated). If second-look surgery reveals mature teratoma or non-viable tumor, proceed to WVSCI. If second-look surgery reveals viable tumor, proceed to HDCSCR. Patients who are unable to undergo second-look surgery are removed from protocol therapy but remain on study for follow-up.

* Patients who achieve less than radiographic CR/PR without marker normalization proceed to second-look surgery (unless contraindicated). Patients then proceed to HDCSCR regardless of whether or not a second-look surgery is performed.

* Patients who achieve radiographic PR without marker normalization proceed to second-look surgery (unless contraindicated). Patients then proceed to HDCSCR regardless of whether or not a second-look surgery is performed.

PLAN A (WVSCI THERAPY): Within 6 weeks of the end of induction chemotherapy or second-look surgery, patients undergo WVSCI once daily (QD) for 5 days weekly (17 fractions followed by a boost dose for 13 fractions) for 6 weeks in the absence of disease progression or unacceptable toxicity.

PLAN B (CONSOLIDATION THERAPY [HDCSCR]): Within 6-8 weeks of the end of induction chemotherapy or second-look surgery, patients receive etoposide IV and thiotepa IV over 3 hours on days -5 to -3 and undergo peripheral blood stem cell (PBSC) transplant on day 0. Patients then undergo radiation therapy QD for 5 days weekly (20 fractions followed by a boost dose for 10 fractions) for 6 weeks in the absence of disease progression or unacceptable toxicity.

Patients also undergo magnetic resonance imaging (MRI), as well as collection of cerebral spinal fluid (CSF) and blood sample throughout the trial.

After completion of study treatment, patients are followed for up to 10 years.

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