Chemotherapy Followed by Radiation Therapy in Treating Younger Patients With Newly Diagnosed Localized Central Nervous System Germ Cell Tumors

• Sponsor: Children's Oncology Group (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT01602666
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 262
• Locations: 167
• Arm: 1
• Anticipated Duration (Months): 139.1
• Patients Per Site: 1.6
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This phase II trial studies how well chemotherapy followed by radiation therapy work in treating younger patients with newly diagnosed central nervous system germ cell tumors that have not spread to other parts of the brain, spinal canal, or body (localized). Drugs used as chemotherapy, such as carboplatin, etoposide, and ifosfamide, 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 to kill tumor cells. Giving chemotherapy followed by radiation therapy may kill more tumor cells.

Condition or Disease	Intervention/Treatment	Phase
Central Nervous System Nongerminomatous Germ Cell Tumor; Childhood Central Nervous System Germinoma	Radiation: 3-Dimensional Conformal Radiation Therapy; Drug: Carboplatin; Drug: Etoposide; Drug: Ifosfamide; Radiation: Intensity-Modulated Radiation Therapy	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To determine, as measured by the 3-year progression-free survival (PFS) rate and patterns of failure, whether dose and volume of irradiation can be safely reduced to 30.6 Gy whole ventricular-field irradiation (WVI) plus 23.4 Gy primary site boost instead of 36 Gy craniospinal irradiation (CSI) plus primary site boost in the subgroup of children and young adults (ages 3 to =< 21 years) with localized nongerminomatous germ cell tumor (NGGCT) who have a magnetic resonance imaging (MRI) and tumor marker criteria (cerebrospinal fluid [CSF] and serum) for confirmed complete response (CR) or partial response (PR) to induction chemotherapy and negative serum and cerebrospinal fluid (CSF) tumor markers OR in patients who have less than a PR after induction chemotherapy with negative tumor markers who undergo a second-look surgery and are found to have only mature teratoma, residual scar or fibrosis and fit the definition of CR/PR after second-look surgery.

2. To determine, as measured by the 3-year PFS rate and patterns of failure, whether simplified chemotherapy followed by dose-reduced radiation therapy is effective for treating children and young adults (ages 3 to =< 21 years) with localized primary central nervous system (CNS) germinoma who present with serum and/or CSF human chorionic gonadotropin-beta (hCGbeta) =< 50 mIU/mL.

3. To prospectively evaluate and longitudinally model the cognitive, social, and behavioral functioning of children and young adults who are treated with reduced radiation dose and volume of irradiation in Stratum 1 (NGGCT) and with dose-reduced radiation therapy in Stratum 2 (germinoma) using the ALTE07C1 protocol.

SECONDARY OBJECTIVES:

1. To estimate the PFS and overall survival (OS) distributions of patients with NGGCT treated with 30.6 Gy WVI and involved-field radiation therapy (IFR) focal boost to 54 Gy.

2. To estimate the PFS and OS distributions of localized germinoma patients who present with

1. serum and/or CSF hCGbeta =< 50 mIU/mL and b) serum and/or CSF hCGbeta > 50 mIU/mL and =< 100 mIU/mL.

OUTLINE:

STRATUM I (NGGCT): Patients receive induction therapy comprising carboplatin intravenously (IV) over 15-60 minutes on day 1 and etoposide IV over 60-120 minutes on days 1-3 of courses 1, 3, and 5. Patients also receive ifosfamide IV over 60 minutes and etoposide over 60-120 minutes on days 1-5 of courses 2, 4, and 6. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients achieving CR or PR undergo 3-dimensional conformal radiation therapy (3DRT) or intensity modulated radiation therapy (IMRT) once daily (QD) 5 days a week for 6 weeks. Patients with normalization of markers who fail to achieve CR or PR are strongly recommended to undergo second-look surgery. Patients who achieve CR or PR after second-look surgery undergo 3DRT or IMRT QD 5 days a week for 6 weeks.

STRATUM II (GERMINOMA): Patients receive induction therapy comprising carboplatin IV over 15-60 minutes on day 1 and etoposide IV over 60-120 minutes on days 1-3. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients with CR or continued CR (CCR) undergo 3DRT or IMRT QD 5 days a week for 4 weeks. Patients with normalization of markers who fail to achieve CR or PR are strongly recommended to undergo second-look surgery. Patients found to have fibrosis, scar, mature teratoma, or non-viable tumor undergo 3DRT or IMRT QD 5 days a week for 4 weeks. Patients with stable disease (SD) or PR with > 0.5 cm (suprasellar) or > 1 cm (pineal) but =< 1.5 cm residual disease do not undergo second-look surgery and undergo 3DRT or IMRT QD 5 days a week for 4 weeks.

After completion of study treatment, patients are followed up at 3, 6, and 9 months, every 4 months for 24 months, 30 months, 36 months, and then annually for up to 60 months.

Study Design

• Study Type: Interventional
• Actual Enrollment: 262 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 2 Trial of Response-Based Radiation Therapy for Patients With Localized Central Nervous System Germ Cell Tumors (CNS GCT)
• Actual Study Start Date: May 29, 2012
• Actual Primary Completion Date: Sep 30, 2019
• Anticipated Study Completion Date: Dec 31, 2023

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Treatment (combination chemotherapy, radiation therapy) See Detailed Description

Radiation: 3-Dimensional Conformal Radiation Therapy; Undergo 3D-CRT; Other Names: 3-dimensional radiation therapy 3D CONFORMAL RADIATION THERAPY 3D CRT 3D-CRT Conformal Therapy Radiation Conformal Therapy Radiation, 3D Conformal ; Drug: Carboplatin; Given IV; Other Names: Blastocarb Carboplat Carboplatin Hexal Carboplatino Carboplatinum Carbosin Carbosol Carbotec CBDCA Displata Ercar JM-8 Nealorin Novoplatinum Paraplatin Paraplatin AQ Paraplatine Platinwas Ribocarbo ; Drug: Etoposide; Given IV; Other Names: Demethyl Epipodophyllotoxin Ethylidine Glucoside EPEG Lastet Toposar Vepesid VP 16 VP 16-213 VP-16 VP-16-213 VP16 ; Drug: Ifosfamide; Given IV; Other Names: Asta Z 4942 Asta Z-4942 Cyfos Holoxan Holoxane Ifex IFO IFO-Cell Ifolem Ifomida Ifomide Ifosfamidum Ifoxan IFX Iphosphamid Iphosphamide Iso-Endoxan Isoendoxan Isophosphamide Mitoxana MJF 9325 MJF-9325 Naxamide Seromida Tronoxal Z 4942 Z-4942 ; Radiation: Intensity-Modulated Radiation Therapy; Undergo IMRT; Other Names: IMRT Intensity Modulated RT Intensity-Modulated Radiotherapy Radiation, Intensity-Modulated Radiotherapy

Outcome Measures

Primary Outcome Measures

1. 3-year Progression-free Survival (PFS) Rate of Patients With Nongerminomatous Germ Cell Tumor (NGGCT) Who Were Treated With Reduced Dose Whole Ventricular-field Irradiation [3 years]

   Binomial estimate of the 3-year PFS rate defined as "Yes" for patients who were followed up per protocol and were progression free at 3-years, and "No" for those who either experienced a progression or were lost to follow-up/withdrew from the trial within 3 years from enrollment. Progression was determined by MRI using the COG Guidelines for Measurement of Tumor Size (>25% increase in 2D or >40% in 3D of the product of perpendicular diameters of the target lesion) as well as by tumor marker assessments which were mandatory for this study.

2. 3-year PFS Rate of Patients With Localized CNS Germinoma Who Were Treated With Reduced Dose Radiation Therapy [3 years]

   Binomial estimate of the 3-year PFS rate defined as "Yes" for patients who were followed up per protocol and were progression free at 3-years, and "No" for those who either experienced a progression or were lost to follow-up/withdrew from the trial within 3 years from initiation of treatment. Progression was determined by MRI using the COG Guidelines for Measurement of Tumor Size (>25% increase in 2D or >40% in 3D of the product of perpendicular diameters of the target lesion) as well as by tumor marker assessments which were mandatory for this study.

3. Neurocognitive Function Using the ALTE07C1 Protocol [Up to 5 years]

   Estimated scores for processing speed, attention/concentration, and estimated IQ at 9 months, 30 months and 60 months, separately for children and young adults who are treated with reduced radiation dose and volume of irradiation in Stratum 1 (NGGCT) and with dose-reduced radiation therapy in Stratum 2 (germinoma). Estimated change over these three timepoints for processing speed, attention/concentration, and estimated IQ, separately for children and young adults who are treated with reduced radiation dose and volume of irradiation in Stratum 1 (NGGCT) and with dose-reduced radiation therapy in Stratum 2 (germinoma).

Secondary Outcome Measures

1. Estimation of the PFS Distribution of Patients With NGGCT Treated With Involved-field Radiation Therapy (IFR) [Up to 3 years]

   Kaplan Meier estimate of the 3-year PFS is provided. PFS is the time interval measured from enrollment until progression or death from any cause or until last follow-up for those who were event free at the time of analysis. Patients who were lost to follow-up or withdrew consent were censored in this analysis. Progression was determined by MRI using the COG Guidelines for Measurement of Tumor Size (>25% increase in 2D or >40% in 3D of the product of perpendicular diameters of the target lesion) as well as by tumor marker assessments which were mandatory for this study.

2. Estimation of the Overall Survival (OS) Distribution of Patients With NGGCT Treated With IFR Assessed [Up to 3 years]

   Kaplan Meier estimate of the 3-year overall survival (OS) is provided. OS is the time interval measured from enrollment until death from any cause or until last follow-up for those who were alive at the time of analysis. Patients who were lost to follow-up or withdrew consent were censored in this analysis.

3. Estimation of the PFS Distribution of Patients With Localized Germinoma Patients and Cerebrospinal Fluid (CSF) Serum hCGbeta of 50 mIU/mL or Less or CSF Serum hCGbeta Greater Than 50 mIU/mL and Less Than or Equal to 100 mIU/mL [Up to 3 years]

   Kaplan Meier estimate of the 3-year PFS rate is provided. PFS is the time interval measured from initiation of treatment until progression or death from any cause or until last follow-up for those who were event free at the time of analysis. Patients who were lost to follow-up or withdrew consent were censored in this analysis. Progression was determined by MRI using the COG Guidelines for Measurement of Tumor Size (>25% increase in 2D or >40% in 3D of the product of perpendicular diameters of the target lesion) as well as by tumor marker assessments which were mandatory for this study.

4. Estimation of the OS Distribution of Patients With Localized Germinoma Patients and CSF Serum hCGbeta of 50 mIU/mL or Less or CSF Serum hCGbeta Greater Than 50 mIU/mL and Less Than or Equal to 100 mIU/mL [Up to 3 years]

   Kaplan Meier estimate of the 3-year overall survival (OS) is provided for each group. OS is the time interval measured from enrollment until death from any cause or until last follow-up for those who were alive at the time of analysis. Patients who were lost to follow-up or withdrew consent were censored in this analysis.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 3 Years to 21 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients must be newly diagnosed with localized primary CNS NGGCT (Stratum 1) or localized primary CNS germinoma (Stratum 2); germ cell tumors located in the suprasellar, pineal, bifocal (pineal + suprasellar) and ventricles are eligible; tumors present in the above mentioned locations and with unifocal parenchymal extension are eligible

• Stratum 1(NGGCT): Patients must have one of the following criteria:

• Patients with serum and/or CSF hCGbeta > 100 mIU/mL or any elevation of serum and/or CSF alpha-fetoprotein (AFP) > 10 ng/mL or greater than the institutional normal are eligible, irrespective of biopsy results

• Patients with any of the following elements on biopsy/resection are eligible, irrespective of serum and/or CSF hCGbeta and AFP levels: endodermal sinus tumor (yolk sac), embryonal carcinoma, choriocarcinoma, malignant/immature teratoma, and mixed GCT with malignant GCT elements

• Stratum 2 (Germinoma): Patients must have both serum and CSF markers obtained (unless obtaining CSF is medically contraindicated) and must have one of the following criteria to be eligible:

• Patients with institutional normal AFP (or =< 10 ng/mL if no institutional normal exists) in both serum and CSF (unless medically contraindicated) AND hCGbeta 5 to =< 50 mIU/mL in serum and/or CSF (unless medically contraindicated) (only 1 is required to be elevated) are eligible; no histologic confirmation required

• Patients with bifocal (pineal + suprasellar) involvement or pineal lesion with diabetes insipidus (D1) AND hCGbeta =< 100 mIU/mL in serum and/or CSF AND institutional normal AFP (or =< 10 ng/mL if no institutional normal exists) in both serum and CSF (unless medically contraindicated) are eligible; no histologic confirmation required

• Patients with histologically confirmed germinoma or germinoma mixed with mature teratoma and hCGbeta =< 100 mIU/mL in serum and/or CSF and institutional normal AFP (or =< 10 ng/mL if no institutional normal exists) in both serum and CSF (unless medically contraindicated) are eligible

• All patients must have a cranial MRI with and without gadolinium at diagnosis/prior to enrollment; if surgical resection is performed, patients must have pre-operative and post-operative cranial MRI with and without gadolinium; the post-operative brain MRI should be obtained within 72 hours of surgery; if patient has a biopsy only, post-operative cranial MRI is recommended but not required; all patients must have a spine MRI with gadolinium obtained at diagnosis/prior to enrollment; Note: if the spine study is performed for the first time after surgical resection or biopsy, it is recommended to be obtained with and without gadolinium

• Lumbar CSF must be obtained prior to study enrollment unless medically contraindicated; if a patient undergoes surgery and lumbar CSF cannot be obtained at this time, then it should be performed at least 10 days following surgery before study enrollment; false positive cytology can occur within 10 days of surgery; Note: patients with positive CSF cytology obtained prior to 10 days after surgery may have cytology repeated to determine eligibility

• Patients must have CSF tumor markers obtained prior to enrollment unless medically contraindicated; ventricular CSF obtained at the time of CSF diversion procedure (if performed) is acceptable for tumor markers but lumbar CSF is preferred; in case CSF diversion and biopsy/surgery are combined, CSF tumor markers should be collected first

• Patients must be enrolled on ALTE07C1 prior to enrollment on ACNS1123; patients must be enrolled within 31 days of definitive diagnostic surgery (day 0) or clinical diagnosis

• Peripheral absolute neutrophil count (ANC) >= 1,000/uL

• Platelet count >= 100,000/uL (transfusion independent)

• Hemoglobin >= 8.0 g/dL (may receive red blood cell [RBC] transfusions)

• Creatinine clearance or radioisotope glomular filtration rate (GFR) >= 70 mL/min/1.73 m^2 OR serum creatinine based on age/gender as follows:

• 0.8 mg/dL (2 to < 6 years of age)

• 1.0 mg/dL (6 to < 10 years of age)

• 1.2 mg/dL (10 to < 13 years of age)

• 1.5 mg/dL (male) and 1.4 mg/dL (female) (13 to < 16 years of age)

• 1.7 mg/dL (male) and 1.4 mg/dL (female) (>= 16 years of age)

• Total bilirubin =< 1.5 times upper limit of normal (ULN) for age

• Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 2.5 times ULN

• Patients with seizure disorder may be enrolled if well controlled

• Patients must not be in status, coma, or assisted ventilation prior to study enrollment

Exclusion Criteria:

• Patients with mature teratoma or completely resected immature teratoma with normal tumor markers are not eligible

• Patients with tumors located outside the ventricles (basal ganglia, thalamus) are not eligible

• Patients with metastatic disease by cranial or spinal MRI evaluation or CSF cytology (unless medically contraindicated) are not eligible

• Patients must not have received any prior tumor-directed therapy other than surgical intervention and corticosteroids

• Female patients who are pregnant are ineligible

• Lactating females are not eligible unless they have agreed not to breastfeed their infants

• Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained

• Sexually active patients of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method for the duration of their study participation

• All patients and/or their parents or legal guardians must sign a written informed consent

• All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital of Alabama	Birmingham	Alabama	United States	35233
2	University of Alabama at Birmingham Cancer Center	Birmingham	Alabama	United States	35233
3	Phoenix Childrens Hospital	Phoenix	Arizona	United States	85016
4	Kaiser Permanente Downey Medical Center	Downey	California	United States	90242
5	Miller Children's and Women's Hospital Long Beach	Long Beach	California	United States	90806
6	Children's Hospital Los Angeles	Los Angeles	California	United States	90027
7	Cedars Sinai Medical Center	Los Angeles	California	United States	90048
8	Mattel Children's Hospital UCLA	Los Angeles	California	United States	90095
9	Valley Children's Hospital	Madera	California	United States	93636
10	Children's Hospital and Research Center at Oakland	Oakland	California	United States	94609-1809
11	Kaiser Permanente-Oakland	Oakland	California	United States	94611
12	Children's Hospital of Orange County	Orange	California	United States	92868
13	Lucile Packard Children's Hospital Stanford University	Palo Alto	California	United States	94304
14	Sutter Medical Center Sacramento	Sacramento	California	United States	95816
15	Rady Children's Hospital - San Diego	San Diego	California	United States	92123
16	UCSF Medical Center-Parnassus	San Francisco	California	United States	94143
17	UCSF Medical Center-Mission Bay	San Francisco	California	United States	94158
18	Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center	Torrance	California	United States	90502
19	Children's Hospital Colorado	Aurora	Colorado	United States	80045
20	Connecticut Children's Medical Center	Hartford	Connecticut	United States	06106
21	Yale University	New Haven	Connecticut	United States	06520
22	Alfred I duPont Hospital for Children	Wilmington	Delaware	United States	19803
23	MedStar Georgetown University Hospital	Washington	District of Columbia	United States	20007
24	Children's National Medical Center	Washington	District of Columbia	United States	20010
25	Lee Memorial Health System	Fort Myers	Florida	United States	33901
26	Golisano Children's Hospital of Southwest Florida	Fort Myers	Florida	United States	33908
27	University of Florida Health Science Center - Gainesville	Gainesville	Florida	United States	32610
28	Memorial Regional Hospital/Joe DiMaggio Children's Hospital	Hollywood	Florida	United States	33021
29	Nemours Children's Clinic-Jacksonville	Jacksonville	Florida	United States	32207
30	University of Miami Miller School of Medicine-Sylvester Cancer Center	Miami	Florida	United States	33136
31	Nicklaus Children's Hospital	Miami	Florida	United States	33155
32	AdventHealth Orlando	Orlando	Florida	United States	32803
33	Arnold Palmer Hospital for Children	Orlando	Florida	United States	32806
34	Nemours Children's Clinic - Orlando	Orlando	Florida	United States	32806
35	UF Cancer Center at Orlando Health	Orlando	Florida	United States	32806
36	Nemours Children's Hospital	Orlando	Florida	United States	32827
37	Nemours Children's Clinic - Pensacola	Pensacola	Florida	United States	32504
38	Johns Hopkins All Children's Hospital	Saint Petersburg	Florida	United States	33701
39	Tampa General Hospital	Tampa	Florida	United States	33606
40	Saint Mary's Hospital	West Palm Beach	Florida	United States	33407
41	Children's Healthcare of Atlanta - Egleston	Atlanta	Georgia	United States	30322
42	Memorial Health University Medical Center	Savannah	Georgia	United States	31404
43	University of Hawaii Cancer Center	Honolulu	Hawaii	United States	96813
44	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii	United States	96826
45	Saint Luke's Mountain States Tumor Institute	Boise	Idaho	United States	83712
46	Lurie Children's Hospital-Chicago	Chicago	Illinois	United States	60611
47	University of Illinois	Chicago	Illinois	United States	60612
48	University of Chicago Comprehensive Cancer Center	Chicago	Illinois	United States	60637
49	Loyola University Medical Center	Maywood	Illinois	United States	60153
50	Advocate Children's Hospital-Oak Lawn	Oak Lawn	Illinois	United States	60453
51	Advocate Children's Hospital-Park Ridge	Park Ridge	Illinois	United States	60068
52	Saint Jude Midwest Affiliate	Peoria	Illinois	United States	61637
53	Riley Hospital for Children	Indianapolis	Indiana	United States	46202
54	Saint Vincent Hospital and Health Care Center	Indianapolis	Indiana	United States	46260
55	Blank Children's Hospital	Des Moines	Iowa	United States	50309
56	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa	United States	52242
57	University of Kentucky/Markey Cancer Center	Lexington	Kentucky	United States	40536
58	Norton Children's Hospital	Louisville	Kentucky	United States	40202
59	Children's Hospital New Orleans	New Orleans	Louisiana	United States	70118
60	University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland	United States	21201
61	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland	United States	21287
62	Walter Reed National Military Medical Center	Bethesda	Maryland	United States	20889-5600
63	Massachusetts General Hospital Cancer Center	Boston	Massachusetts	United States	02114
64	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
65	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan	United States	48201
66	Michigan State University Clinical Center	East Lansing	Michigan	United States	48824-7016
67	Helen DeVos Children's Hospital at Spectrum Health	Grand Rapids	Michigan	United States	49503
68	Bronson Methodist Hospital	Kalamazoo	Michigan	United States	49007
69	Children's Hospitals and Clinics of Minnesota - Minneapolis	Minneapolis	Minnesota	United States	55404
70	Mayo Clinic in Rochester	Rochester	Minnesota	United States	55905
71	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216
72	Children's Mercy Hospitals and Clinics	Kansas City	Missouri	United States	64108
73	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
74	Mercy Hospital Saint Louis	Saint Louis	Missouri	United States	63141
75	University Medical Center of Southern Nevada	Las Vegas	Nevada	United States	89102
76	Alliance for Childhood Diseases/Cure 4 the Kids Foundation	Las Vegas	Nevada	United States	89135
77	Summerlin Hospital Medical Center	Las Vegas	Nevada	United States	89144
78	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756
79	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
80	Saint Barnabas Medical Center	Livingston	New Jersey	United States	07039
81	Morristown Medical Center	Morristown	New Jersey	United States	07960
82	Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital	New Brunswick	New Jersey	United States	08903
83	Newark Beth Israel Medical Center	Newark	New Jersey	United States	07112
84	Overlook Hospital	Summit	New Jersey	United States	07902
85	University of New Mexico Cancer Center	Albuquerque	New Mexico	United States	87102
86	Albany Medical Center	Albany	New York	United States	12208
87	Montefiore Medical Center - Moses Campus	Bronx	New York	United States	10467
88	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
89	NYU Winthrop Hospital	Mineola	New York	United States	11501
90	The Steven and Alexandra Cohen Children's Medical Center of New York	New Hyde Park	New York	United States	11040
91	Laura and Isaac Perlmutter Cancer Center at NYU Langone	New York	New York	United States	10016
92	NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center	New York	New York	United States	10032
93	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
94	University of Rochester	Rochester	New York	United States	14642
95	State University of New York Upstate Medical University	Syracuse	New York	United States	13210
96	New York Medical College	Valhalla	New York	United States	10595
97	Mission Hospital	Asheville	North Carolina	United States	28801
98	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina	United States	27599
99	Carolinas Medical Center/Levine Cancer Institute	Charlotte	North Carolina	United States	28203
100	Novant Health Presbyterian Medical Center	Charlotte	North Carolina	United States	28204
101	Duke University Medical Center	Durham	North Carolina	United States	27710
102	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157
103	Sanford Broadway Medical Center	Fargo	North Dakota	United States	58122
104	Children's Hospital Medical Center of Akron	Akron	Ohio	United States	44308
105	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229
106	Rainbow Babies and Childrens Hospital	Cleveland	Ohio	United States	44106
107	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
108	Nationwide Children's Hospital	Columbus	Ohio	United States	43205
109	Dayton Children's Hospital	Dayton	Ohio	United States	45404
110	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
111	Legacy Emanuel Children's Hospital	Portland	Oregon	United States	97227
112	Oregon Health and Science University	Portland	Oregon	United States	97239
113	Lehigh Valley Hospital-Cedar Crest	Allentown	Pennsylvania	United States	18103
114	Lehigh Valley Hospital - Muhlenberg	Bethlehem	Pennsylvania	United States	18017
115	Penn State Children's Hospital	Hershey	Pennsylvania	United States	17033
116	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
117	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania	United States	15224
118	Prisma Health Richland Hospital	Columbia	South Carolina	United States	29203
119	BI-LO Charities Children's Cancer Center	Greenville	South Carolina	United States	29605
120	Greenville Cancer Treatment Center	Greenville	South Carolina	United States	29605
121	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota	United States	57117-5134
122	T C Thompson Children's Hospital	Chattanooga	Tennessee	United States	37403
123	East Tennessee Childrens Hospital	Knoxville	Tennessee	United States	37916
124	Saint Jude Children's Research Hospital	Memphis	Tennessee	United States	38105
125	Vanderbilt University/Ingram Cancer Center	Nashville	Tennessee	United States	37232
126	Dell Children's Medical Center of Central Texas	Austin	Texas	United States	78723
127	Driscoll Children's Hospital	Corpus Christi	Texas	United States	78411
128	Medical City Dallas Hospital	Dallas	Texas	United States	75230
129	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas	United States	75390
130	Cook Children's Medical Center	Fort Worth	Texas	United States	76104
131	Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center	Houston	Texas	United States	77030
132	M D Anderson Cancer Center	Houston	Texas	United States	77030
133	UMC Cancer Center / UMC Health System	Lubbock	Texas	United States	79415
134	Children's Hospital of San Antonio	San Antonio	Texas	United States	78207
135	Methodist Children's Hospital of South Texas	San Antonio	Texas	United States	78229
136	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78229
137	Primary Children's Hospital	Salt Lake City	Utah	United States	84113
138	University of Virginia Cancer Center	Charlottesville	Virginia	United States	22908
139	Inova Fairfax Hospital	Falls Church	Virginia	United States	22042
140	Children's Hospital of The King's Daughters	Norfolk	Virginia	United States	23507
141	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia	United States	23298
142	Carilion Children's	Roanoke	Virginia	United States	24014
143	Seattle Children's Hospital	Seattle	Washington	United States	98105
144	Providence Sacred Heart Medical Center and Children's Hospital	Spokane	Washington	United States	99204
145	Madigan Army Medical Center	Tacoma	Washington	United States	98431
146	Saint Vincent Hospital Cancer Center Green Bay	Green Bay	Wisconsin	United States	54301
147	University of Wisconsin Hospital and Clinics	Madison	Wisconsin	United States	53792
148	Marshfield Medical Center-Marshfield	Marshfield	Wisconsin	United States	54449
149	Children's Hospital of Wisconsin	Milwaukee	Wisconsin	United States	53226
150	John Hunter Children's Hospital	Hunter Regional Mail Centre	New South Wales	Australia	2310
151	Sydney Children's Hospital	Randwick	New South Wales	Australia	2031
152	The Children's Hospital at Westmead	Westmead	New South Wales	Australia	2145
153	Royal Children's Hospital-Brisbane	Herston	Queensland	Australia	4029
154	Queensland Children's Hospital	South Brisbane	Queensland	Australia	4101
155	Women's and Children's Hospital-Adelaide	North Adelaide	South Australia	Australia	5006
156	Royal Children's Hospital	Parkville	Victoria	Australia	3052
157	Princess Margaret Hospital for Children	Perth	Western Australia	Australia	6008
158	Perth Children's Hospital	Perth	Western Australia	Australia	6009
159	British Columbia Children's Hospital	Vancouver	British Columbia	Canada	V6H 3V4
160	CancerCare Manitoba	Winnipeg	Manitoba	Canada	R3E 0V9
161	IWK Health Centre	Halifax	Nova Scotia	Canada	B3K 6R8
162	McMaster Children's Hospital at Hamilton Health Sciences	Hamilton	Ontario	Canada	L8N 3Z5
163	Hospital for Sick Children	Toronto	Ontario	Canada	M5G 1X8
164	Centre Hospitalier Universitaire Sainte-Justine	Montreal	Quebec	Canada	H3T 1C5
165	Starship Children's Hospital	Grafton	Auckland	New Zealand	1145
166	Christchurch Hospital	Christchurch		New Zealand	8011
167	University Pediatric Hospital	San Juan		Puerto Rico	00926

Sponsors and Collaborators

• Children's Oncology Group
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Ute K Bartels, Children's Oncology Group

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jun 1, 2015

More Information

Publications

None provided.

• Responsible Party: Children's Oncology Group
• ClinicalTrials.gov Identifier: NCT01602666
• Other Study ID Numbers: ACNS1123; NCI-2012-01967; ACNS1123; CDR0000734032; S12-02807; ACNS1123; ACNS1123; K12CA086913; U10CA180886; U10CA098543
• First Posted: May 21, 2012
• Last Update Posted: Dec 13, 2021
• Last Verified: Dec 1, 2021

• Additional relevant MeSH terms: Neoplasms, Germ Cell and Embryonal; Germinoma; Carboplatin; Etoposide; Etoposide phosphate; Ifosfamide; Isophosphamide mustard; Podophyllotoxin

Study Results

Participant Flow

Recruitment Details	Patients enrolled on the study from 05/29/2012 to 11/01/2016 on Stratum 1 and from 05/29/2012 to 10/26/2018 on Stratum 2
Pre-assignment Detail	There were 111 patients enrolled in Stratum 1 with localized nongerminomatous germ cell tumors (NGGCT) and 151 patients enrolled in Stratum 2 with localized CNS Germinoma (Germinoma). Of these 107 in Stratum 1 and 137 in Stratum 2 were deemed eligible for the study. This report is limited to eligible subjects.

Arm/Group Title	Stratum 1 Localized Non-Germinomatous Germ Cell Tumors (NGGCT)	Stratum 2 Localized Germinoma
Arm/Group Description	Patients receive induction therapy comprising carboplatin intravenously (IV) over 15-60 minutes on day 1 and etoposide IV over 60-120 minutes on days 1-3 of courses 1, 3, and 5. Patients also receive ifosfamide IV over 60 minutes and etoposide over 60-120 minutes on days 1-5 of courses 2, 4, and 6. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients achieving CR or PR undergo 3-dimensional conformal radiation therapy (3DRT) or intensity modulated radiation therapy (IMRT) once daily (QD) 5 days a week for 6 weeks. Patients with normalization of markers who fail to achieve CR or PR are strongly recommended to undergo second-look surgery. Patients who achieve CR or PR after second-look surgery undergo 3DRT or IMRT QD 5 days a week for 6 weeks.	Patients receive induction therapy comprising carboplatin IV over 15-60 minutes on day 1 and etoposide IV over 60-120 minutes on days 1-3. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients with CR or continued CR (CCR) undergo 3DRT or IMRT QD 5 days a week for 4 weeks. Patients with normalization of markers who fail to achieve CR or PR are strongly recommended to undergo second-look surgery. Patients found to have fibrosis, scar, mature teratoma, or non-viable tumor undergo 3DRT or IMRT QD 5 days a week for 4 weeks. Patients with stable disease (SD) or PR with > 0.5 cm (suprasellar) or > 1 cm (pineal) but =< 1.5 cm residual disease do not undergo second-look surgery and undergo 3DRT or IMRT QD 5 days a week for 4 weeks.
Period Title: Induction Chemotherapy
STARTED	107	137
COMPLETED	70	113
NOT COMPLETED	37	24
Period Title: Induction Chemotherapy
STARTED	70	113
Evaluable for Reduced Dose (30Gy)	66	0
Evaluable for Reduced Dose (18 Gy)	0	74
Evaluable for RT Dose (24Gy)	0	16
COMPLETED	60	82
NOT COMPLETED	10	31

Baseline Characteristics

Arm/Group Title	Stratum 1 Localized Non-Germinomatous Germ Cell Tumors (NGGCT)	Stratum 2 Localized Germinoma	Total
Arm/Group Description	Patients receive induction therapy comprising carboplatin intravenously (IV) over 15-60 minutes on day 1 and etoposide IV over 60-120 minutes on days 1-3 of courses 1, 3, and 5. Patients also receive ifosfamide IV over 60 minutes and etoposide over 60-120 minutes on days 1-5 of courses 2, 4, and 6. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients achieving CR or PR undergo 3-dimensional conformal radiation therapy (3DRT) or intensity modulated radiation therapy (IMRT) once daily (QD) 5 days a week for 6 weeks. Patients with normalization of markers who fail to achieve CR or PR are strongly recommended to undergo second-look surgery. Patients who achieve CR or PR after second-look surgery undergo 3DRT or IMRT QD 5 days a week for 6 weeks.	Patients receive induction therapy comprising carboplatin IV over 15-60 minutes on day 1 and etoposide IV over 60-120 minutes on days 1-3. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients with CR or continued CR (CCR) undergo 3DRT or IMRT QD 5 days a week for 4 weeks. Patients with normalization of markers who fail to achieve CR or PR are strongly recommended to undergo second-look surgery. Patients found to have fibrosis, scar, mature teratoma, or non-viable tumor undergo 3DRT or IMRT QD 5 days a week for 4 weeks. Patients with stable disease (SD) or PR with > 0.5 cm (suprasellar) or > 1 cm (pineal) but =< 1.5 cm residual disease do not undergo second-look surgery and undergo 3DRT or IMRT QD 5 days a week for 4 weeks.	Total of all reporting groups
Overall Participants	107	137	244
Age (Count of Participants)
<=18 years	100 93.5%	124 90.5%	224 91.8%
Between 18 and 65 years	7 6.5%	13 9.5%	20 8.2%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	11.0	14.1	13.0
Sex: Female, Male (Count of Participants)
Female	27 25.2%	37 27%	64 26.2%
Male	80 74.8%	100 73%	180 73.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	20 18.7%	16 11.7%	36 14.8%
Not Hispanic or Latino	83 77.6%	113 82.5%	196 80.3%
Unknown or Not Reported	4 3.7%	8 5.8%	12 4.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	8 7.5%	14 10.2%	22 9%
Native Hawaiian or Other Pacific Islander	1 0.9%	8 5.8%	9 3.7%
Black or African American	6 5.6%	9 6.6%	15 6.1%
White	78 72.9%	86 62.8%	164 67.2%
More than one race	0 0%	1 0.7%	1 0.4%
Unknown or Not Reported	14 13.1%	19 13.9%	33 13.5%
Region of Enrollment (participants) [Number]
United States	93 86.9%	117 85.4%	210 86.1%
Australia	7 6.5%	10 7.3%	17 7%
Canada	7 6.5%	6 4.4%	13 5.3%
New Zealand	0 0%	4 2.9%	4 1.6%

Outcome Measures

1. Primary Outcome

Title	3-year Progression-free Survival (PFS) Rate of Patients With Nongerminomatous Germ Cell Tumor (NGGCT) Who Were Treated With Reduced Dose Whole Ventricular-field Irradiation
Description	Binomial estimate of the 3-year PFS rate defined as "Yes" for patients who were followed up per protocol and were progression free at 3-years, and "No" for those who either experienced a progression or were lost to follow-up/withdrew from the trial within 3 years from enrollment. Progression was determined by MRI using the COG Guidelines for Measurement of Tumor Size (>25% increase in 2D or >40% in 3D of the product of perpendicular diameters of the target lesion) as well as by tumor marker assessments which were mandatory for this study.
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

Localized NGGCT treated with 30.6 Gy WVF RT + 23.4 Gy primary site boost. Patients must have had complete response (CR) or partial response (PR) to induction chemotherapy by MRI and markers; or underwent second-look surgery and were found to have mature teratoma, residual scar or fibrosis and fit the definition of CR/PR after second-look surgery.

Arm/Group Title	Stratum 1 Localized Non-Germinomatous Germ Cell Tumors (NGGCT)
Arm/Group Description	Patients receive induction therapy comprising carboplatin intravenously (IV) over 15-60 minutes on day 1 and etoposide IV over 60-120 minutes on days 1-3 of courses 1, 3, and 5. Patients also receive ifosfamide IV over 60 minutes and etoposide over 60-120 minutes on days 1-5 of courses 2, 4, and 6. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients achieving CR or PR undergo 3-dimensional conformal radiation therapy (3DRT) or intensity modulated radiation therapy (IMRT) once daily (QD) 5 days a week for 6 weeks. Patients with normalization of markers who fail to achieve CR or PR are strongly recommended to undergo second-look surgery. Patients who achieve CR or PR after second-look surgery undergo 3DRT or IMRT QD 5 days a week for 6 weeks.
Measure Participants	66
Number (95% Confidence Interval) [percentage of patients]	83.33

2. Primary Outcome

Title	3-year PFS Rate of Patients With Localized CNS Germinoma Who Were Treated With Reduced Dose Radiation Therapy
Description	Binomial estimate of the 3-year PFS rate defined as "Yes" for patients who were followed up per protocol and were progression free at 3-years, and "No" for those who either experienced a progression or were lost to follow-up/withdrew from the trial within 3 years from initiation of treatment. Progression was determined by MRI using the COG Guidelines for Measurement of Tumor Size (>25% increase in 2D or >40% in 3D of the product of perpendicular diameters of the target lesion) as well as by tumor marker assessments which were mandatory for this study.
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

Localized CNS Germinoma treated with dose-reduced RT (18 Gy WVI + 12 Gy primary site boost) and had complete response (CR) after induction chemotherapy by MRI and tumor marker criteria; or underwent second-look surgery and were found to have mature teratoma, residual scar or fibrosis and fit the definition of CR after second-look surgery.

Arm/Group Title	Stratum 2 Localized Germinoma
Arm/Group Description	Patients receive induction therapy comprising carboplatin IV over 15-60 minutes on day 1 and etoposide IV over 60-120 minutes on days 1-3. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients with CR or continued CR (CCR) undergo 3DRT or IMRT QD 5 days a week for 4 weeks. Patients with normalization of markers who fail to achieve CR or PR are strongly recommended to undergo second-look surgery. Patients found to have fibrosis, scar, mature teratoma, or non-viable tumor undergo 3DRT or IMRT QD 5 days a week for 4 weeks. Patients with stable disease (SD) or PR with > 0.5 cm (suprasellar) or > 1 cm (pineal) but =< 1.5 cm residual disease do not undergo second-look surgery and undergo 3DRT or IMRT QD 5 days a week for 4 weeks.
Measure Participants	74
Number (95% Confidence Interval) [percentage of patients]	86.49

3. Primary Outcome

Title	Neurocognitive Function Using the ALTE07C1 Protocol
Description	Estimated scores for processing speed, attention/concentration, and estimated IQ at 9 months, 30 months and 60 months, separately for children and young adults who are treated with reduced radiation dose and volume of irradiation in Stratum 1 (NGGCT) and with dose-reduced radiation therapy in Stratum 2 (germinoma). Estimated change over these three timepoints for processing speed, attention/concentration, and estimated IQ, separately for children and young adults who are treated with reduced radiation dose and volume of irradiation in Stratum 1 (NGGCT) and with dose-reduced radiation therapy in Stratum 2 (germinoma).
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Estimation of the PFS Distribution of Patients With NGGCT Treated With Involved-field Radiation Therapy (IFR)
Description	Kaplan Meier estimate of the 3-year PFS is provided. PFS is the time interval measured from enrollment until progression or death from any cause or until last follow-up for those who were event free at the time of analysis. Patients who were lost to follow-up or withdrew consent were censored in this analysis. Progression was determined by MRI using the COG Guidelines for Measurement of Tumor Size (>25% increase in 2D or >40% in 3D of the product of perpendicular diameters of the target lesion) as well as by tumor marker assessments which were mandatory for this study.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

Localized NGGCT treated with 30.6 Gy WVF RT + 23.4 Gy primary site boost. Patients must have had complete response (CR) or partial response (PR) to induction chemotherapy by MRI and markers; or underwent second-look surgery and were found to have mature teratoma, residual scar or fibrosis and fit the definition of CR/PR after second-look surgery.

Arm/Group Title	Stratum 1 Localized Non-Germinomatous Germ Cell Tumors (NGGCT)
Arm/Group Description	Patients receive induction therapy comprising carboplatin intravenously (IV) over 15-60 minutes on day 1 and etoposide IV over 60-120 minutes on days 1-3 of courses 1, 3, and 5. Patients also receive ifosfamide IV over 60 minutes and etoposide over 60-120 minutes on days 1-5 of courses 2, 4, and 6. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients achieving CR or PR undergo 3-dimensional conformal radiation therapy (3DRT) or intensity modulated radiation therapy (IMRT) once daily (QD) 5 days a week for 6 weeks. Patients with normalization of markers who fail to achieve CR or PR are strongly recommended to undergo second-look surgery. Patients who achieve CR or PR after second-look surgery undergo 3DRT or IMRT QD 5 days a week for 6 weeks.
Measure Participants	66
Number (95% Confidence Interval) [percentage of patients]	87.88

5. Secondary Outcome

Title	Estimation of the Overall Survival (OS) Distribution of Patients With NGGCT Treated With IFR Assessed
Description	Kaplan Meier estimate of the 3-year overall survival (OS) is provided. OS is the time interval measured from enrollment until death from any cause or until last follow-up for those who were alive at the time of analysis. Patients who were lost to follow-up or withdrew consent were censored in this analysis.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

Localized NGGCT treated with 30.6 Gy WVF RT + 23.4 Gy primary site boost. Patients must have had complete response (CR) or partial response (PR) to induction chemotherapy by MRI and markers; or underwent second-look surgery and were found to have mature teratoma, residual scar or fibrosis and fit the definition of CR/PR after second-look surgery.

Arm/Group Title	Stratum 1 Localized Non-Germinomatous Germ Cell Tumors (NGGCT)
Arm/Group Description	Patients receive induction therapy comprising carboplatin intravenously (IV) over 15-60 minutes on day 1 and etoposide IV over 60-120 minutes on days 1-3 of courses 1, 3, and 5. Patients also receive ifosfamide IV over 60 minutes and etoposide over 60-120 minutes on days 1-5 of courses 2, 4, and 6. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients achieving CR or PR undergo 3-dimensional conformal radiation therapy (3DRT) or intensity modulated radiation therapy (IMRT) once daily (QD) 5 days a week for 6 weeks. Patients with normalization of markers who fail to achieve CR or PR are strongly recommended to undergo second-look surgery. Patients who achieve CR or PR after second-look surgery undergo 3DRT or IMRT QD 5 days a week for 6 weeks.
Measure Participants	66
Number (95% Confidence Interval) [percentage of patients]	92.42

6. Secondary Outcome

Title	Estimation of the PFS Distribution of Patients With Localized Germinoma Patients and Cerebrospinal Fluid (CSF) Serum hCGbeta of 50 mIU/mL or Less or CSF Serum hCGbeta Greater Than 50 mIU/mL and Less Than or Equal to 100 mIU/mL
Description	Kaplan Meier estimate of the 3-year PFS rate is provided. PFS is the time interval measured from initiation of treatment until progression or death from any cause or until last follow-up for those who were event free at the time of analysis. Patients who were lost to follow-up or withdrew consent were censored in this analysis. Progression was determined by MRI using the COG Guidelines for Measurement of Tumor Size (>25% increase in 2D or >40% in 3D of the product of perpendicular diameters of the target lesion) as well as by tumor marker assessments which were mandatory for this study.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

The eligible patients with localized germinoma and CSF serum hCGbeta of 50 mIU/mL or less or CSF serum hCGbeta greater than 50 mIU/mL and less than or equal to 100 mIU/mL.

Arm/Group Title	hCGbeta <= 50 mIU/mL	50 mIU/mL < hCGbeta <= 100 mIU/mL
Arm/Group Description	CSF/serum hCGbeta <= 50 mIU/mL	50 mIU/mL < CSF /serum hCGbeta <= 100 mIU/mL
Measure Participants	131	6
Number (95% Confidence Interval) [percentage of patients]	93.26	80.00

7. Secondary Outcome

Title	Estimation of the OS Distribution of Patients With Localized Germinoma Patients and CSF Serum hCGbeta of 50 mIU/mL or Less or CSF Serum hCGbeta Greater Than 50 mIU/mL and Less Than or Equal to 100 mIU/mL
Description	Kaplan Meier estimate of the 3-year overall survival (OS) is provided for each group. OS is the time interval measured from enrollment until death from any cause or until last follow-up for those who were alive at the time of analysis. Patients who were lost to follow-up or withdrew consent were censored in this analysis.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

The eligible patients with localized germinoma and CSF serum hCGbeta of 50 mIU/mL or less or CSF serum hCGbeta greater than 50 mIU/mL and less than or equal to 100 mIU/mL

Arm/Group Title	hCGbeta <= 50 mIU/mL	50 mIU/mL < hCGbeta <= 100 mIU/mL
Arm/Group Description	CSF/serum hCGbeta <= 50 mIU/mL	50 mIU/mL < CSF /serum hCGbeta <= 100 mIU/mL
Measure Participants	131	6
Number (95% Confidence Interval) [percentage of patients]	98.38	100

Adverse Events

Time Frame	From initiation of induction of therapy to the date of last follow-up, approximately 3 years. For most subjects the adverse events were observed while on active treatment or shortly thereafter.
Adverse Event Reporting Description	Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. Ineligible patients are excluded from reporting of adverse events. All-Cause Mortality includes all deaths collected on the study.
Arm/Group Title	Stratum 1 Localized Non-Germinomatous Germ Cell Tumors (NGGCT)		Stratum 2 Localized Germinoma
Arm/Group Description	Patients receive induction therapy comprising carboplatin intravenously (IV) over 15-60 minutes on day 1 and etoposide IV over 60-120 minutes on days 1-3 of courses 1, 3, and 5. Patients also receive ifosfamide IV over 60 minutes and etoposide over 60-120 minutes on days 1-5 of courses 2, 4, and 6. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients achieving CR or PR undergo 3-dimensional conformal radiation therapy (3DRT) or intensity modulated radiation therapy (IMRT) once daily (QD) 5 days a week for 6 weeks. Patients with normalization of markers who fail to achieve CR or PR are strongly recommended to undergo second-look surgery. Patients who achieve CR or PR after second-look surgery undergo 3DRT or IMRT QD 5 days a week for 6 weeks.		Patients receive induction therapy comprising carboplatin IV over 15-60 minutes on day 1 and etoposide IV over 60-120 minutes on days 1-3. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients with CR or continued CR (CCR) undergo 3DRT or IMRT QD 5 days a week for 4 weeks. Patients with normalization of markers who fail to achieve CR or PR are strongly recommended to undergo second-look surgery. Patients found to have fibrosis, scar, mature teratoma, or non-viable tumor undergo 3DRT or IMRT QD 5 days a week for 4 weeks. Patients with stable disease (SD) or PR with > 0.5 cm (suprasellar) or > 1 cm (pineal) but =< 1.5 cm residual disease do not undergo second-look surgery and undergo 3DRT or IMRT QD 5 days a week for 4 weeks.
All Cause Mortality
	Stratum 1 Localized Non-Germinomatous Germ Cell Tumors (NGGCT)		Stratum 2 Localized Germinoma
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/107 (12.1%)		2/137 (1.5%)
Serious Adverse Events
	Stratum 1 Localized Non-Germinomatous Germ Cell Tumors (NGGCT)		Stratum 2 Localized Germinoma
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/107 (4.7%)		1/137 (0.7%)
Blood and lymphatic system disorders
Anemia	0/107 (0%)	0	1/137 (0.7%)	1
Febrile neutropenia	1/107 (0.9%)	1	1/137 (0.7%)	1
Infections and infestations
Sepsis	1/107 (0.9%)	1	0/137 (0%)	0
Nervous system disorders
Headache	1/107 (0.9%)	1	0/137 (0%)	0
Hydrocephalus	1/107 (0.9%)	1	0/137 (0%)	0
Intracranial hemorrhage	1/107 (0.9%)	1	0/137 (0%)	0
Respiratory, thoracic and mediastinal disorders
Respiratory failure	1/107 (0.9%)	1	0/137 (0%)	0
Other (Not Including Serious) Adverse Events
	Stratum 1 Localized Non-Germinomatous Germ Cell Tumors (NGGCT)		Stratum 2 Localized Germinoma
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	84/107 (78.5%)		107/137 (78.1%)
Blood and lymphatic system disorders
Anemia	45/107 (42.1%)	99	48/137 (35%)	101
Blood and lymphatic system disorders - Other- Specify	1/107 (0.9%)	1	0/137 (0%)	0
Febrile neutropenia	19/107 (17.8%)	28	22/137 (16.1%)	31
Cardiac disorders
Sinus tachycardia	1/107 (0.9%)	1	0/137 (0%)	0
Ear and labyrinth disorders
Hearing impaired	1/107 (0.9%)	1	0/137 (0%)	0
Endocrine disorders
Adrenal insufficiency	0/107 (0%)	0	1/137 (0.7%)	1
Endocrine disorders - Other- Specify	0/107 (0%)	0	2/137 (1.5%)	2
Eye disorders
Eye pain	1/107 (0.9%)	1	0/137 (0%)	0
Gastrointestinal disorders
Abdominal pain	2/107 (1.9%)	2	2/137 (1.5%)	2
Anal mucositis	1/107 (0.9%)	1	0/137 (0%)	0
Anal pain	0/107 (0%)	0	1/137 (0.7%)	1
Diarrhea	1/107 (0.9%)	1	1/137 (0.7%)	1
Mucositis oral	1/107 (0.9%)	1	0/137 (0%)	0
Nausea	3/107 (2.8%)	3	4/137 (2.9%)	5
Pancreatitis	1/107 (0.9%)	1	0/137 (0%)	0
Vomiting	7/107 (6.5%)	8	6/137 (4.4%)	9
General disorders
Fatigue	1/107 (0.9%)	1	0/137 (0%)	0
Hypothermia	1/107 (0.9%)	1	0/137 (0%)	0
Infusion related reaction	1/107 (0.9%)	1	0/137 (0%)	0
Irritability	1/107 (0.9%)	1	0/137 (0%)	0
Multi-organ failure	1/107 (0.9%)	1	0/137 (0%)	0
Pain	0/107 (0%)	0	1/137 (0.7%)	1
Immune system disorders
Allergic reaction	0/107 (0%)	0	3/137 (2.2%)	3
Anaphylaxis	1/107 (0.9%)	1	0/137 (0%)	0
Infections and infestations
Appendicitis	0/107 (0%)	0	1/137 (0.7%)	1
Catheter related infection	3/107 (2.8%)	4	0/137 (0%)	0
Enterocolitis infectious	1/107 (0.9%)	1	0/137 (0%)	0
Infections and infestations - Other- Specify	3/107 (2.8%)	7	1/137 (0.7%)	1
Lung infection	2/107 (1.9%)	2	1/137 (0.7%)	1
Lymph gland infection	0/107 (0%)	0	1/137 (0.7%)	1
Mucosal infection	1/107 (0.9%)	1	0/137 (0%)	0
Otitis media	0/107 (0%)	0	1/137 (0.7%)	1
Sepsis	2/107 (1.9%)	2	0/137 (0%)	0
Soft tissue infection	0/107 (0%)	0	2/137 (1.5%)	2
Upper respiratory infection	3/107 (2.8%)	3	2/137 (1.5%)	2
Urinary tract infection	0/107 (0%)	0	1/137 (0.7%)	1
Investigations
Alanine aminotransferase increased	10/107 (9.3%)	13	15/137 (10.9%)	23
Aspartate aminotransferase increased	2/107 (1.9%)	2	1/137 (0.7%)	1
Blood bilirubin increased	2/107 (1.9%)	2	1/137 (0.7%)	1
CPK increased	1/107 (0.9%)	1	0/137 (0%)	0
Electrocardiogram QT corrected interval prolonged	0/107 (0%)	0	1/137 (0.7%)	1
GGT increased	1/107 (0.9%)	3	1/137 (0.7%)	1
INR increased	1/107 (0.9%)	1	0/137 (0%)	0
Lymphocyte count decreased	31/107 (29%)	85	11/137 (8%)	12
Lymphocyte count increased	0/107 (0%)	0	1/137 (0.7%)	1
Neutrophil count decreased	66/107 (61.7%)	210	92/137 (67.2%)	266
Platelet count decreased	54/107 (50.5%)	126	83/137 (60.6%)	213
Weight gain	1/107 (0.9%)	1	1/137 (0.7%)	1
White blood cell decreased	52/107 (48.6%)	150	50/137 (36.5%)	88
Metabolism and nutrition disorders
Acidosis	1/107 (0.9%)	1	0/137 (0%)	0
Anorexia	6/107 (5.6%)	7	2/137 (1.5%)	2
Dehydration	6/107 (5.6%)	7	8/137 (5.8%)	10
Hyperglycemia	3/107 (2.8%)	4	4/137 (2.9%)	5
Hyperkalemia	2/107 (1.9%)	2	2/137 (1.5%)	2
Hypermagnesemia	0/107 (0%)	0	2/137 (1.5%)	2
Hypernatremia	18/107 (16.8%)	33	14/137 (10.2%)	15
Hypocalcemia	1/107 (0.9%)	1	2/137 (1.5%)	2
Hypokalemia	11/107 (10.3%)	17	15/137 (10.9%)	19
Hyponatremia	23/107 (21.5%)	32	14/137 (10.2%)	21
Hypophosphatemia	2/107 (1.9%)	2	5/137 (3.6%)	7
Obesity	0/107 (0%)	0	1/137 (0.7%)	1
Musculoskeletal and connective tissue disorders
Avascular necrosis	0/107 (0%)	0	1/137 (0.7%)	1
Back pain	0/107 (0%)	0	1/137 (0.7%)	2
Bone pain	1/107 (0.9%)	1	0/137 (0%)	0
Chest wall pain	1/107 (0.9%)	1	0/137 (0%)	0
Growth suppression	1/107 (0.9%)	1	0/137 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign- malignant and unspecified (incl cysts and polyps) - Other- Specify	6/107 (5.6%)	6	0/137 (0%)	0
Nervous system disorders
Ataxia	1/107 (0.9%)	1	0/137 (0%)	0
Cerebrospinal fluid leakage	1/107 (0.9%)	1	0/137 (0%)	0
Cognitive disturbance	3/107 (2.8%)	3	0/137 (0%)	0
Depressed level of consciousness	4/107 (3.7%)	4	1/137 (0.7%)	1
Dysphasia	1/107 (0.9%)	1	0/137 (0%)	0
Edema cerebral	0/107 (0%)	0	1/137 (0.7%)	1
Encephalopathy	5/107 (4.7%)	5	0/137 (0%)	0
Headache	7/107 (6.5%)	8	2/137 (1.5%)	2
Hydrocephalus	5/107 (4.7%)	6	0/137 (0%)	0
Hypersomnia	0/107 (0%)	0	1/137 (0.7%)	1
Intracranial hemorrhage	1/107 (0.9%)	1	0/137 (0%)	0
Meningismus	1/107 (0.9%)	1	0/137 (0%)	0
Nervous system disorders - Other- Specify	0/107 (0%)	0	1/137 (0.7%)	1
Paresthesia	1/107 (0.9%)	1	0/137 (0%)	0
Seizure	2/107 (1.9%)	2	0/137 (0%)	0
Somnolence	3/107 (2.8%)	4	0/137 (0%)	0
Syncope	1/107 (0.9%)	1	3/137 (2.2%)	4
Psychiatric disorders
Confusion	0/107 (0%)	0	1/137 (0.7%)	1
Delirium	1/107 (0.9%)	1	0/137 (0%)	0
Insomnia	0/107 (0%)	0	1/137 (0.7%)	1
Mania	1/107 (0.9%)	1	0/137 (0%)	0
Suicidal ideation	0/107 (0%)	0	1/137 (0.7%)	1
Renal and urinary disorders
Acute kidney injury	1/107 (0.9%)	1	0/137 (0%)	0
Renal and urinary disorders - Other- Specify	1/107 (0.9%)	1	1/137 (0.7%)	1
Respiratory, thoracic and mediastinal disorders
Aspiration	0/107 (0%)	0	1/137 (0.7%)	1
Epistaxis	4/107 (3.7%)	4	1/137 (0.7%)	1
Hypoxia	1/107 (0.9%)	1	0/137 (0%)	0
Skin and subcutaneous tissue disorders
Photosensitivity	0/107 (0%)	0	1/137 (0.7%)	1
Vascular disorders
Hypertension	1/107 (0.9%)	1	0/137 (0%)	0
Hypotension	3/107 (2.8%)	3	1/137 (0.7%)	1
Thromboembolic event	3/107 (2.8%)	3	0/137 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Must obtain prior approval