Surgery and Combination Chemotherapy in Treating Children With Extracranial Germ Cell Tumors

• Sponsor: Children's Oncology Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT00053352
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 302
• Locations: 126
• Arms: 2
• Actual Duration (Months): 211.9
• Patients Per Site: 2.4
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This phase III trial is studying surgery followed by combination chemotherapy to see how well it works in treating children with germ cell tumors that are not located in the head. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug, and giving them after surgery, may kill any remaining tumor cells following surgery. It is not yet known whether combination chemotherapy is effective in decreasing the recurrence of childhood germ cell tumors.

Condition or Disease	Intervention/Treatment	Phase
Childhood Embryonal Tumor; Childhood Extracranial Germ Cell Tumor; Childhood Extragonadal Germ Cell Tumor; Childhood Malignant Ovarian Germ Cell Tumor; Childhood Malignant Testicular Germ Cell Tumor; Childhood Teratoma; Ovarian Embryonal Carcinoma; Ovarian Yolk Sac Tumor; Stage II Malignant Testicular Germ Cell Tumor; Stage IIA Ovarian Germ Cell Tumor; Stage IIB Ovarian Germ Cell Tumor; Stage IIC Ovarian Germ Cell Tumor; Stage III Malignant Testicular Germ Cell Tumor; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIC Ovarian Germ Cell Tumor; Testicular Choriocarcinoma and Yolk Sac Tumor; Testicular Embryonal Carcinoma	Procedure: conventional surgery; Drug: cisplatin; Drug: etoposide; Biological: bleomycin sulfate; Other: laboratory biomarker analysis	Phase 3

Detailed Description

OBJECTIVES:

1. Determine whether children with newly diagnosed low- or intermediate-risk extracranial germ cell tumors (GCTs) can maintain a 3-year event-free survival of at least 92% (for intermediate-risk tumors only) and overall survival of at least 95% (both low-risk and intermediate-risk tumors) after treatment with surgery followed by compressed cisplatin, etoposide, and bleomycin (low-risk disease closed to accrual as of 01/20/10).

2. Determine the percentage of patients with stage I ovarian or stage I testicular GCTs for whom chemotherapy can be eliminated.

3. Determine the percentage of intermediate-risk patients who require only 3 courses of therapy.

4. Determine the acute toxic effects of compressed therapy in these patients. V. Determine the long-term sequelae in patients treated with this regimen. VI. Determine the number of hospital days and total drug doses required for patients treated with compressed therapy.

5. Compare the number of protocol-directed treatment days used in CCG-8882 vs the number of treatment days used in this study.

6. Determine the cytogenetic and molecular genetic features in patients treated with this regimen.

OUTLINE: Patients are stratified according to disease risk (low vs intermediate).

SURGERY: Patients undergo surgical resection.

Low-risk disease: Patients with gonadal primaries and no evidence of disease after surgery undergo monitoring for disease progression. Patients who remain disease free receive no further treatment. Patients who have disease progression after surgery receive compressed induction chemotherapy. (closed to accrual as of 01/20/2010)

Intermediate-risk disease: After surgery, patients proceed to compressed induction chemotherapy.

COMPRESSED INDUCTION CHEMOTHERAPY: Patients receive cisplatin IV over 90 minutes and etoposide IV over 90 minutes on days 1-3 and bleomycin IV over ≥ 10 minutes on day 1. Treatment repeats every 3 weeks for 3 courses (weeks 0, 3, and 6).

After completion of compressed induction chemotherapy, patients who have no change in disease status or disease progression are removed from study. Patients with no evidence of disease receive no further therapy. Patients with a partial response or who have abnormal tumor markers proceed to second-look surgery and/or 3 more courses of compressed consolidation chemotherapy.

SECOND-LOOK SURGERY: Patients undergo surgical resection of residual tumor. After surgery, patients who are in pathologic complete response and have normal tumor markers receive no further therapy. Patients who remain with a partial response after surgery receive compressed consolidation chemotherapy.

COMPRESSED CONSOLIDATION CHEMOTHERAPY: Patients receive cisplatin, etoposide, and bleomycin as in induction chemotherapy in weeks 10, 13, and 16.

Patients are followed up monthly for 6 months, every 3 months for 18 months, and then annually for up to 10 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 302 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase III Study Of Reduced Therapy In The Treatment Of Children With Low And Intermediate Risk Extracranial Germ Cell Tumors
• Actual Study Start Date: Nov 3, 2003
• Actual Primary Completion Date: Oct 1, 2013
• Actual Study Completion Date: Jun 30, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I Patients enrolled with gonadal tumors of stage II or greater or extragonadal tumors of any stage receive cisplatin IV over 90 minutes & etoposide IV over 90 minutes days 1-3 and bleomycin sulfate IV over ≥ 10 minutes day 1. Treatment repeats every 3 weeks, 3 courses (weeks 0,3 & 6). After completion of compressed induction chemotherapy, patients with no change in disease status or disease progression are removed from study. Patients with no evidence of disease receive no further therapy. Patients with a partial response or abnormal tumor markers proceed to conventional surgery (second-look) and/or 3 more courses of compressed consolidation chemotherapy. After surgery, patients with pathologic complete response and have normal tumor markers receive no further therapy. Patients who remain with a partial response after surgery receive compressed consolidation chemotherapy. Patients receive cisplatin, etoposide, and bleomycin as induction chemotherapy in weeks 10,13, & 16.	Procedure: conventional surgery; Other Names: surgery, conventional ; Drug: cisplatin; Given IV; Other Names: CACP CDDP CPDD DDP ; Drug: etoposide; Given IV; Other Names: EPEG VP-16 VP-16-213 ; Biological: bleomycin sulfate; Given IV; Other Names: Blenoxane BLEO BLM ; Other: laboratory biomarker analysis; Correlative studies
No Intervention: Arm 2 Patients who are enrolled with stage I gonadal tumors receive no further anticancer therapy until evidence of tumor recurrence or the diagnosis of a second malignant neoplasm. Observation only for recurrence or development of an SMN

Outcome Measures

Primary Outcome Measures

1. Event-Free Survival (EFS) [3 Years after enrollment]

   Proportion of patients event free at 3 years following enrollment. Event-free survival is not a primary outcome measure for Arm 2 patients.

2. Overall Survival (OS) [3 Years after enrollment]

   Percentage probability of being alive at 3 years following enrollment.

Secondary Outcome Measures

1. Days Hospitalized for Patients Who Receive Chemotherapy [Up to 126 days after the start of chemotherapy]

   Calculated to quantify the treatment cost associated with this regimen.

2. Toxicity Associated With Chemotherapy: Grade 3 or Higher. Toxicity as Assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v4.0 [Up to 126 days after the start of chemotherapy]

   The number of patients assigned to receive chemotherapy that experience CTC Version 4 grade 3 or higher at any time during protocol therapy

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 21 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Extracranial germ cell tumor that contains 1 of the following malignant histologies: NOTE: Mixed germ cell tumors that include mature/immature teratoma are eligible provided 1 of the 3 histologies listed above is also present in the tumor.

• Yolk sac tumor

• Embryonal carcinoma

• Choriocarcinoma

• Low-risk disease (closed to accrual as of 01/20/10)

• Stage I gonadal tumors (ovarian and testicular)

• Must have undergone complete surgical and radiologic staging to exclude the possibility of > stage I disease

• Intermediate-risk disease

• Stage II, III, or IV malignant testicular GCT

• Stage II or III malignant ovarian GCT

• Stage I or II malignant extragonadal GCT

• Previously stage I gonadal patients who have relapsed on the low-risk (observation) stratum of this study(closed to accrual as of 01/20/10)

• Patients with immature teratoma or mature teratoma who relapse with a malignant component

• No patients with any of the following diagnoses:

• Stage IV ovarian and stage III-IV extragonadal GCT

• Intracranial GCT

• Pure mature or immature teratoma, pure dysgerminoma, or seminoma

• Patients with a non-germ cell component in their GCT (e.g., primitive neuroectodermal tumors or rhabdomyosarcoma)

• Alpha-fetoprotein and beta human chorionic gonadotropin tumor markers known

• If > 5 days have elapsed from the time of obtaining original markers, tumor markers must be repeated before enrollment of low-risk patients and before initiating therapy in intermediate-risk patients (the results of the repeated tumor markers do not have to be known at the time of study enrollment)

• Must be enrolled within 6 weeks of original diagnostic surgery

• Creatinine clearance or radioisotope GFR ≥ 70 mL/min OR a serum creatinine based on age/gender as follows:

• ≤ 0.4 mg/dL (for patients 1 to 5 months of age)

• ≤ 0.5 mg/dL (for patients 6 to 11 months of age)

• ≤ 0.6 mg/dL (for patients 1 year of age)

• ≤ 0.8 mg/dL (for patients 2 to 5 years of age)

• ≤ 1.0 mg/dL (for patients 6 to 9 years of age)

• ≤ 1.2 mg/dL (for patients 10 to 12 years of age)

• ≤ 1.4 mg/dL (for female patients ≥ 13 years of age)

• ≤ 1.5 mg/dL (for male patients 13 to 15 years of age)

• ≤ 1.7 mg/dL (for male patients ≥ 16 years of age)

• No prior chemotherapy

• No prior radiotherapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294
2	Phoenix Childrens Hospital	Phoenix	Arizona	United States	85016
3	University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205
4	Southern California Permanente Medical Group	Downey	California	United States	90242
5	Loma Linda University Medical Center	Loma Linda	California	United States	92354
6	Miller Children's Hospital	Long Beach	California	United States	90806
7	Children's Hospital Los Angeles	Los Angeles	California	United States	90027
8	Children's Hospital Central California	Madera	California	United States	93636-8762
9	Children's Hospital and Research Center at Oakland	Oakland	California	United States	94609-1809
10	Kaiser Permanente-Oakland	Oakland	California	United States	94611
11	Childrens Hospital of Orange County	Orange	California	United States	92868-3874
12	Lucile Packard Children's Hospital Stanford University	Palo Alto	California	United States	94304
13	Sutter General Hospital	Sacramento	California	United States	95816
14	Rady Children's Hospital - San Diego	San Diego	California	United States	92123
15	University of California San Francisco Medical Center-Parnassus	San Francisco	California	United States	94143
16	Children's Hospital Colorado	Aurora	Colorado	United States	80045
17	Connecticut Children's Medical Center	Hartford	Connecticut	United States	06106
18	Yale University	New Haven	Connecticut	United States	06520-8032
19	Alfred I duPont Hospital for Children	Wilmington	Delaware	United States	19803
20	Children's National Medical Center	Washington	District of Columbia	United States	20010
21	Broward Health Medical Center	Fort Lauderdale	Florida	United States	33316
22	Lee Memorial Health System	Fort Myers	Florida	United States	33901
23	University of Florida	Gainesville	Florida	United States	32610
24	Memorial Healthcare System - Joe DiMaggio Children's Hospital	Hollywood	Florida	United States	33021
25	University of Miami Miller School of Medicine-Sylvester Cancer Center	Miami	Florida	United States	33136
26	Miami Children's Hospital	Miami	Florida	United States	33155
27	All Children's Hospital	Saint Petersburg	Florida	United States	33701
28	Children's Healthcare of Atlanta - Egleston	Atlanta	Georgia	United States	30322
29	Memorial Health University Medical Center	Savannah	Georgia	United States	31403
30	University of Hawaii	Honolulu	Hawaii	United States	96813
31	Saint Luke's Mountain States Tumor Institute	Boise	Idaho	United States	83712
32	Childrens Memorial Hospital	Chicago	Illinois	United States	60614
33	Loyola University Medical Center	Maywood	Illinois	United States	60153
34	Advocate Hope Children's Hospital	Oak Lawn	Illinois	United States	60453
35	Saint Jude Midwest Affiliate	Peoria	Illinois	United States	61602
36	Southern Illinois University	Springfield	Illinois	United States	62702
37	University of Kentucky	Lexington	Kentucky	United States	40536
38	Kosair Children's Hospital	Louisville	Kentucky	United States	40202
39	Massachusetts General Hospital Cancer Center	Boston	Massachusetts	United States	02114
40	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115
41	Baystate Medical Center	Springfield	Massachusetts	United States	01199
42	C S Mott Children's Hospital	Ann Arbor	Michigan	United States	48109
43	Wayne State University	Detroit	Michigan	United States	48202
44	Saint John Hospital and Medical Center	Detroit	Michigan	United States	48236
45	Hurley Medical Center	Flint	Michigan	United States	48502
46	Helen DeVos Children's Hospital at Spectrum Health	Grand Rapids	Michigan	United States	49503
47	Michigan State University - Breslin Cancer Center	Lansing	Michigan	United States	48910
48	Children's Hospitals and Clinics of Minnesota - Minneapolis	Minneapolis	Minnesota	United States	55404
49	University of Minnesota Medical Center-Fairview	Minneapolis	Minnesota	United States	55455
50	Mayo Clinic	Rochester	Minnesota	United States	55905
51	The Childrens Mercy Hospital	Kansas City	Missouri	United States	64108
52	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
53	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756
54	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
55	Saint Peter's University Hospital	New Brunswick	New Jersey	United States	08901
56	UMDNJ - Robert Wood Johnson University Hospital	New Brunswick	New Jersey	United States	08903
57	Newark Beth Israel Medical Center	Newark	New Jersey	United States	07112
58	Albany Medical Center	Albany	New York	United States	12208
59	Montefiore Medical Center	Bronx	New York	United States	10467-2490
60	Brooklyn Hospital Center	Brooklyn	New York	United States	11201
61	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
62	The Steven and Alexandra Cohen Children's Medical Center of New York	New Hyde Park	New York	United States	11040
63	New York University Langone Medical Center	New York	New York	United States	10016
64	Columbia University Medical Center	New York	New York	United States	10032
65	University of Rochester	Rochester	New York	United States	14642
66	State University of New York Upstate Medical University	Syracuse	New York	United States	13210
67	New York Medical College	Valhalla	New York	United States	10595
68	Mission Hospitals Inc	Asheville	North Carolina	United States	28801
69	Duke University Medical Center	Durham	North Carolina	United States	27710
70	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157
71	Sanford Medical Center-Fargo	Fargo	North Dakota	United States	58122
72	Children's Hospital Medical Center of Akron	Akron	Ohio	United States	44308
73	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229
74	Rainbow Babies and Childrens Hospital	Cleveland	Ohio	United States	44106
75	Nationwide Children's Hospital	Columbus	Ohio	United States	43205
76	The Children's Medical Center of Dayton	Dayton	Ohio	United States	45404
77	Mercy Children's Hospital	Toledo	Ohio	United States	43608
78	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
79	Legacy Emanuel Hospital and Health Center	Portland	Oregon	United States	97227
80	Oregon Health and Science University	Portland	Oregon	United States	97239
81	Geisinger Medical Center	Danville	Pennsylvania	United States	17822-2001
82	Penn State Hershey Children's Hospital	Hershey	Pennsylvania	United States	17033
83	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
84	Saint Christopher's Hospital for Children	Philadelphia	Pennsylvania	United States	19134
85	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania	United States	15224
86	Medical University of South Carolina	Charleston	South Carolina	United States	29425
87	Palmetto Health Richland	Columbia	South Carolina	United States	29203
88	T C Thompson Children's Hospital	Chattanooga	Tennessee	United States	37403
89	East Tennessee Childrens Hospital	Knoxville	Tennessee	United States	37916
90	St. Jude Children's Research Hospital	Memphis	Tennessee	United States	38105
91	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee	United States	37232
92	Texas Tech University Health Science Center-Amarillo	Amarillo	Texas	United States	79106
93	Dell Children's Medical Center of Central Texas	Austin	Texas	United States	78723
94	Driscoll Children's Hospital	Corpus Christi	Texas	United States	78411
95	University of Texas Southwestern Medical Center	Dallas	Texas	United States	75390
96	Cook Children's Medical Center	Fort Worth	Texas	United States	76104
97	Baylor College of Medicine	Houston	Texas	United States	77030
98	M D Anderson Cancer Center	Houston	Texas	United States	77030
99	Covenant Children's Hospital	Lubbock	Texas	United States	79410
100	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78229-3900
101	Methodist Children's Hospital of South Texas	San Antonio	Texas	United States	78229
102	Scott and White Memorial Hospital	Temple	Texas	United States	76508
103	Primary Children's Medical Center	Salt Lake City	Utah	United States	84113
104	University of Vermont	Burlington	Vermont	United States	05401
105	Childrens Hospital-King's Daughters	Norfolk	Virginia	United States	23507
106	Carilion Clinic Children's Hospital	Roanoke	Virginia	United States	24014
107	Seattle Children's Hospital	Seattle	Washington	United States	98105
108	West Virginia University Charleston	Charleston	West Virginia	United States	25304
109	Saint Vincent Hospital	Green Bay	Wisconsin	United States	54301
110	University of Wisconsin Hospital and Clinics	Madison	Wisconsin	United States	53792
111	Marshfield Clinic	Marshfield	Wisconsin	United States	54449
112	Midwest Children's Cancer Center	Milwaukee	Wisconsin	United States	53226
113	The Children's Hospital at Westmead	Sydney	New South Wales	Australia	2145
114	Princess Margaret Hospital for Children	Perth	Western Australia	Australia	6008
115	Alberta Children's Hospital	Calgary	Alberta	Canada	T3B 6A8
116	University of Alberta Hospital	Edmonton	Alberta	Canada	T6G 2B7
117	British Columbia Children's Hospital	Vancouver	British Columbia	Canada	V6H 3V4
118	Chedoke-McMaster Hospitals	Hamilton	Ontario	Canada	L8S 4L8
119	Cancer Centre of Southeastern Ontario at Kingston General Hospital	Kingston	Ontario	Canada	K7L 5P9
120	Hospital for Sick Children	Toronto	Ontario	Canada	M5G 1X8
121	Hospital Sainte-Justine	Montreal	Quebec	Canada	H3T 1C5
122	Centre Hospitalier Universitaire de Quebec	Ste-Foy	Quebec	Canada	G1V 4G2
123	Allan Blair Cancer Centre	Regina	Saskatchewan	Canada	S4T 7T1
124	Starship Children's Hospital	Grafton	Auckland	New Zealand	1145
125	San Jorge Children's Hospital	Santurce		Puerto Rico	00912
126	Swiss Pediatric Oncology Group - Geneva	Geneva		Switzerland	1205

Sponsors and Collaborators

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

Investigators

• Principal Investigator: Anne Frazier, MD, Children's Oncology Group

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Data Available: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive

Publications

None provided.

• Responsible Party: Children's Oncology Group
• ClinicalTrials.gov Identifier: NCT00053352
• Other Study ID Numbers: AGCT0132; NCI-2009-00373; CDR0000269433; COG-AGCT0132; U10CA098543
• First Posted: Jan 28, 2003
• Last Update Posted: Jul 13, 2021
• Last Verified: Jul 1, 2021

• Additional relevant MeSH terms: Carcinoma; Neoplasms; Neoplasms, Germ Cell and Embryonal; Germinoma; Ovarian Neoplasms; Teratoma; Testicular Neoplasms; Carcinoma, Embryonal; Endodermal Sinus Tumor; Choriocarcinoma; Etoposide; Etoposide phosphate; Bleomycin

Study Results

Participant Flow

Arm/Group Title	Arm I	Arm 2
Arm/Group Description	Experimental	No intervention
Period Title: Overall Study
STARTED	190	112
COMPLETED	169	102
NOT COMPLETED	21	10

Baseline Characteristics

Arm/Group Title	Arm I	Arm 2	Total
Arm/Group Description	Experimental	No intervention	Total of all reporting groups
Overall Participants	190	112	302
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	9.57 (5.65)	5.41 (5.93)	8.02 (6.09)
Sex: Female, Male (Count of Participants)
Female	145 76.3%	29 25.9%	174 57.6%
Male	45 23.7%	83 74.1%	128 42.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 0.5%	1 0.9%	2 0.7%
Asian	14 7.4%	10 8.9%	24 7.9%
Native Hawaiian or Other Pacific Islander	1 0.5%	3 2.7%	4 1.3%
Black or African American	22 11.6%	8 7.1%	30 9.9%
White	128 67.4%	72 64.3%	200 66.2%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	24 12.6%	18 16.1%	42 13.9%
Region of Enrollment (participants) [Number]
New Zealand	2 1.1%	3 2.7%	5 1.7%
Canada	16 8.4%	8 7.1%	24 7.9%
United States	170 89.5%	91 81.3%	261 86.4%
Australia	1 0.5%	8 7.1%	9 3%
Switzerland	0 0%	2 1.8%	2 0.7%
Guam	1 0.5%	0 0%	1 0.3%

Outcome Measures

1. Primary Outcome

Title	Event-Free Survival (EFS)
Description	Proportion of patients event free at 3 years following enrollment. Event-free survival is not a primary outcome measure for Arm 2 patients.
Time Frame	3 Years after enrollment

Outcome Measure Data

Analysis Population Description

181 patients were evaluated for event free survival through 3 years for patients enrolled on Arm 1. Event-free survival is not a primary outcome measure for Arm 2 patients.

Arm/Group Title	Arm 1
Arm/Group Description	Experimental
Measure Participants	181
Number (95% Confidence Interval) [Percent probability]	87.0

2. Primary Outcome

Title	Overall Survival (OS)
Description	Percentage probability of being alive at 3 years following enrollment.
Time Frame	3 Years after enrollment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm I	Arm 2
Arm/Group Description	Experimental	No intervention
Measure Participants	181	104
Number (95% Confidence Interval) [Percent Probability]	97.0	99.0

3. Secondary Outcome

Title	Days Hospitalized for Patients Who Receive Chemotherapy
Description	Calculated to quantify the treatment cost associated with this regimen.
Time Frame	Up to 126 days after the start of chemotherapy

Outcome Measure Data

Analysis Population Description

182 patients were enrolled on intermediate risk chemotherapy and were evaluable for this secondary endpoint

Arm/Group Title	Arm I
Arm/Group Description	Experimental
Measure Participants	182
Mean (Standard Deviation) [Days in the hospital]	14.08 (10.27)

4. Secondary Outcome

Title	Toxicity Associated With Chemotherapy: Grade 3 or Higher. Toxicity as Assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v4.0
Description	The number of patients assigned to receive chemotherapy that experience CTC Version 4 grade 3 or higher at any time during protocol therapy
Time Frame	Up to 126 days after the start of chemotherapy

Outcome Measure Data

Analysis Population Description

182 patients were enrolled on intermediate risk chemotherapy and were evaluable for this secondary endpoint

Arm/Group Title	Arm I
Arm/Group Description	Experimental
Measure Participants	182
Abdominal pain	3
Acute kidney injury	1
Lymphocyte count decrease	2
Iincrease in alanine aminotransferase	1
Neutrophil count decrease	58
Anemia	10
Increase in aspartate aminotransferase	1
Catheter related infection	1
Constipation	1
Dehydration	1
Encephalopathy	1
Febrile neutropenia	9
Fever	3
Hyperglycemia	1
Hyperkalemia	1
Hypocalcemia	2
Hypokalemia	1
Hypomagnesemia	1
Hyponatremia	1
Hypophosphatemia	6
Small intestine obstruction	1
Nausea	5
Non-cardiac chest pain	1
Other gastrointestinal disorders	1
Other infection	10
Platelet count decrease	7
Syncope	1
Vomiting	4
White blood cell decrease	17
Wound infection	1

Adverse Events

Adverse Event Reporting Description	Only patients who are considered eligible contribute to the tabulation of adverse events. For Arm/Group Title "No Intervention" (Arm/Group Description: "Arm 2") 104 eligible patients contribute as described from the Participant Flow as 112 enrolled minus 8 ineligible. For Arm/Group Title "Experimental" (Arm/Group Description: "Arm 1") 182 eligible patients contribute as described from the Participant Flow as 190 enrolled minus 8 ineligible.
Arm/Group Title	Arm 2 (Observation)		Arm I (Chemotherapy)
Arm/Group Description	Patients who are enrolled with stage I gonadal tumors receive no further anticancer therapy until evidence of tumor recurrence or the diagnosis of a second malignant neoplasm. Observation only for recurrence or development of an SMN		Patients enrolled with gonadal tumors of stage II or greater or extragonadal tumors of any stage receive cisplatin IV over 90 minutes & etoposide IV over 90 minutes days 1-3 and bleomycin sulfate IV over ≥ 10 minutes day 1. Treatment repeats every 3 weeks, 3 courses (weeks 0,3 & 6). After completion of compressed induction chemotherapy, patients with no change in disease status or disease progression are removed from study. Patients with no evidence of disease receive no further therapy. Patients with a partial response or abnormal tumor markers proceed to conventional surgery (2nd-look) and/or 3 more courses of compressed consolidation chemotherapy. After surgery, patients with pathologic complete response and have normal tumor markers receive no further therapy. Patients who remain with a partial response after surgery receive compressed consolidation chemotherapy. Patients receive cisplatin, etoposide, and bleomycin as induction chemotherapy in weeks 10,13, & 16. con
All Cause Mortality
	Arm 2 (Observation)		Arm I (Chemotherapy)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm 2 (Observation)		Arm I (Chemotherapy)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/104 (0%)		0/182 (0%)
Other (Not Including Serious) Adverse Events
	Arm 2 (Observation)		Arm I (Chemotherapy)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/104 (0%)		78/182 (42.9%)
Blood and lymphatic system disorders
Anemia	0/104 (0%)		10/182 (5.5%)
Febrile neutropenia	0/104 (0%)		9/182 (4.9%)
Ear and labyrinth disorders
Hearing impaired	0/104 (0%)		1/182 (0.5%)
Gastrointestinal disorders
Abdominal pain	0/104 (0%)		3/182 (1.6%)
Constipation	0/104 (0%)		1/182 (0.5%)
Gastrointestinal disorders - Other, specify	0/104 (0%)		1/182 (0.5%)
Ileus	0/104 (0%)		0/182 (0%)
Nausea	0/104 (0%)		5/182 (2.7%)
Small intestinal obstruction	0/104 (0%)		1/182 (0.5%)
Vomiting	0/104 (0%)		4/182 (2.2%)
General disorders
Fever	0/104 (0%)		3/182 (1.6%)
Non-cardiac chest pain	0/104 (0%)		1/182 (0.5%)
Infections and infestations
Catheter related infection	0/104 (0%)		1/182 (0.5%)
Infections and infestations - Other, specify	0/104 (0%)		10/182 (5.5%)
Urinary tract infection	0/104 (0%)		0/182 (0%)
Wound infection	0/104 (0%)		1/182 (0.5%)
Investigations
Alanine aminotransferase increased	0/104 (0%)		1/182 (0.5%)
Aspartate aminotransferase increased	0/104 (0%)		1/182 (0.5%)
Lymphocyte count decreased	0/104 (0%)		2/182 (1.1%)
Neutrophil count decreased	0/104 (0%)		58/182 (31.9%)
Platelet count decreased	0/104 (0%)		7/182 (3.8%)
White blood cell decreased	0/104 (0%)		17/182 (9.3%)
Metabolism and nutrition disorders
Dehydration	0/104 (0%)		1/182 (0.5%)
Hyperglycemia	0/104 (0%)		1/182 (0.5%)
Hyperkalemia	0/104 (0%)		1/182 (0.5%)
Hypocalcemia	0/104 (0%)		2/182 (1.1%)
Hypokalemia	0/104 (0%)		1/182 (0.5%)
Hypomagnesemia	0/104 (0%)		1/182 (0.5%)
Hyponatremia	0/104 (0%)		1/182 (0.5%)
Hypophosphatemia	0/104 (0%)		6/182 (3.3%)
Nervous system disorders
Encephalopathy	0/104 (0%)		1/182 (0.5%)
Syncope	0/104 (0%)		1/182 (0.5%)
Renal and urinary disorders
Acute kidney injury	0/104 (0%)		1/182 (0.5%)

Limitations/Caveats

Only patients considered eligible contribute to the tabulation of AEs. Arm 1: 182 eligible as described in Participant Flow as 190 enrolled, -8 ineligible. Arm 2: 104 eligible as described in Participant Flow as 112 enrolled, -8 ineligible.

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Certain Agreements

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

Must obtain prior Sponsor approval.