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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03067181




Registration number
NCT03067181
Ethics application status
Date submitted
14/02/2017
Date registered
23/02/2017
Date last updated
15/02/2019

Titles & IDs
Public title
Active Surveillance, Bleomycin, Carboplatin, Etoposide, or Cisplatin in Treating Pediatric and Adult Patients With Germ Cell Tumors
Scientific title
A Phase 3 Study of Active Surveillance for Low Risk and a Randomized Trial of Carboplatin vs. Cisplatin for Standard Risk Pediatric and Adult Patients With Germ Cell Tumors
Secondary ID [1] 0 0
NCI-2017-00178
Secondary ID [2] 0 0
AGCT1531
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Adult Germ Cell Tumor 0 0
Childhood Extracranial Germ Cell Tumor 0 0
Childhood Germ Cell Tumor 0 0
Extragonadal Embryonal Carcinoma 0 0
Grade 2 Immature Ovarian Teratoma 0 0
Grade 3 Immature Ovarian Teratoma 0 0
Malignant Germ Cell Tumor 0 0
Stage I Ovarian Choriocarcinoma 0 0
Stage I Ovarian Embryonal Carcinoma 0 0
Stage I Ovarian Teratoma 0 0
Stage I Ovarian Yolk Sac Tumor 0 0
Stage I Testicular Choriocarcinoma AJCC v6 and v7 0 0
Stage I Testicular Embryonal Carcinoma AJCC v6 and v7 0 0
Stage I Testicular Yolk Sac Tumor AJCC v6 and v7 0 0
Stage II Ovarian Choriocarcinoma 0 0
Stage II Ovarian Embryonal Carcinoma 0 0
Stage II Ovarian Yolk Sac Tumor 0 0
Stage II Testicular Choriocarcinoma AJCC v6 and v7 0 0
Stage II Testicular Embryonal Carcinoma AJCC v6 and v7 0 0
Stage II Testicular Yolk Sac Tumor AJCC v6 and v7 0 0
Stage III Ovarian Choriocarcinoma 0 0
Stage III Ovarian Embryonal Carcinoma 0 0
Stage III Ovarian Yolk Sac Tumor 0 0
Stage III Testicular Choriocarcinoma AJCC v6 and v7 0 0
Stage III Testicular Embryonal Carcinoma AJCC v6 and v7 0 0
Stage III Testicular Yolk Sac Tumor AJCC v6 and v7 0 0
Stage IV Ovarian Choriocarcinoma 0 0
Stage IV Ovarian Embryonal Carcinoma 0 0
Stage IV Ovarian Yolk Sac Tumor 0 0
Testicular Mixed Choriocarcinoma and Embryonal Carcinoma 0 0
Testicular Mixed Choriocarcinoma and Teratoma 0 0
Testicular Mixed Choriocarcinoma and Yolk Sac Tumor 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney
Cancer 0 0 0 0
Ovarian and primary peritoneal
Cancer 0 0 0 0
Testicular
Cancer 0 0 0 0
Other cancer types
Cancer 0 0 0 0
Womb (Uterine or endometrial cancer)
Reproductive Health and Childbirth 0 0 0 0
Fetal medicine and complications of pregnancy

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Best Practice
Treatment: Drugs - Bleomycin
Other interventions - Bleomycin Sulfate
Treatment: Drugs - Carboplatin
Treatment: Drugs - Cisplatin
Treatment: Drugs - Etoposide
Treatment: Drugs - Etoposide Phosphate
Other interventions - Laboratory Biomarker Analysis
Other interventions - Pharmacogenomic Study
Other interventions - Quality-of-Life Assessment
Other interventions - Questionnaire Administration

Experimental: Arm I (bleomycin, carboplatin, etoposide) - Patients receive bleomycin IV over 10 minutes and carboplatin IV over 1 hour on day 1. Patients also receive etoposide IV over 1-2 hours on days 1-5. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

Experimental: Arm II (bleomycin, etoposide, cisplatin) - Patients receive bleomycin IV over 10 minutes on day 1. Patients also receive etoposide IV over 1-2 hours and cisplatin IV over 1-3 hours on days 1-5. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

Experimental: Arm III (bleomycin, etoposide, carboplatin) - Patients receive bleomycin IV over 10 minutes on days 1, 8, and 15, etoposide IV over 1-2 hours on days 1-5, and carboplatin IV over 1 hour on day 1. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.

Experimental: Arm IV (bleomycin, etoposide, cisplatin) - Patients receive bleomycin IV over 10 minutes on days 1, 8, and 15, etoposide IV over 1-2 hours on days 1-5, and cisplatin IV over 1-3 hours on days 1-5. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.

Experimental: Low-Risk (observation) - Patients with stage I grade 2, 3 ovarian immature teratoma or low-risk stage I malignant germ cell tumors undergo observation and can transfer to standard risk arm when eligibility criteria are met.


Other interventions: Best Practice
Undergo observation

Treatment: Drugs: Bleomycin
Given IV

Other interventions: Bleomycin Sulfate
Given IV

Treatment: Drugs: Carboplatin
Given IV

Treatment: Drugs: Cisplatin
Given IV

Treatment: Drugs: Etoposide
Given IV

Treatment: Drugs: Etoposide Phosphate
Given IV

Other interventions: Laboratory Biomarker Analysis
Correlative studies

Other interventions: Pharmacogenomic Study
Correlative studies

Other interventions: Quality-of-Life Assessment
Ancillary studies

Other interventions: Questionnaire Administration
Ancillary studies

Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall survival - A 1-sided lower 85% confidence limit for the 2-year survival will be constructed, and if this confidence limit is greater than 0.95, it will be concluded that the strategy provides sufficient overall survival.
Timepoint [1] 0 0
The time from randomization to date of date of death or date of last follow-up and ascertained as alive, assessed up to 8 years
Primary outcome [2] 0 0
Event-free survival - Will compare between a carboplatin-based regimen versus a cisplatin-based regimen.
Timepoint [2] 0 0
The time from study entry to the date of death, date of disease progression or recurrence, date of second malignant neoplasm or date of last contact and ascertained as alive, whichever comes first, assessed up to 5 years
Secondary outcome [1] 0 0
Incidence of ototoxicity - Will compare the proportion of patients who demonstrate hearing loss according to the International Society of Pediatric Oncology criteria.
Timepoint [1] 0 0
4 weeks after the last dose of platin therapy
Secondary outcome [2] 0 0
Content validity and understandability of Adolescents and Young Adults-Hearing Screen - Will be assessed by questionnaire.
Timepoint [2] 0 0
Baseline

Eligibility
Key inclusion criteria
- Low risk stratum (stage I ovarian immature teratoma and stage I malignant GCT [all
sites]): Patients must be < 50 years of age at enrollment

- Standard risk 1: Patient must be < 11 years of age at enrollment

- Standard risk 2: Patients must be >= 11 and < 25 years of age at enrollment

- Newly diagnosed patients must have histologic verification of a primary extracranial
germ cell tumor in any of the categories outlined; elevation of serum tumor markers
without histologic confirmation is not sufficient for entry on the trial

- NOTE: for low risk patients, materials for rapid surgical central review must be
sent within 7 days of study enrollment

- Low risk stage I immature teratoma (IT); site: ovarian; stage: Children's Oncology
Group (COG) stage I, Federation of Gynecology and Obstetrics (FIGO) stage IA and IB;
grade: 2 or 3; histology: pure immature teratoma (may contain =< 5% of microscopic
yolk sac tumor), mixed immature and mature teratoma, (no pathological evidence of
mediastinal germ cell tumor [MGCT]); tumor markers: alpha-FP =< 1,000 ng/mL, beta-HCG
institutional normal; age (years) < 50

- Low risk stage I MCGT; site: ovarian, testicular, or extragonadal; stage: COG stage I,
FIGO stage IA and IB, American Joint Committee on Cancer (AJCC) testicular stage IA,
IB and IS; histology: must contain at least one of the following: yolk sac tumor,
embryonal carcinoma, or choriocarcinoma (pure or mixed); age (years) < 50

- Standard risk 1 (SR1); site: ovarian, testicular, or extragonadal; stage: COG stage
II-IV, FIGO stage IC, FIGO stage II-IV; histology: must contain at least one of the
following: yolk sac tumor, embryonal carcinoma, or choriocarcinoma (pure or mixed);
age (years) < 11

- Standard risk 2 (SR2)

- Site: ovarian; stage: COG stage II and III, FIGO stage IC, II and III; histology:
must contain at least one of the following: yolk sac tumor, embryonal carcinoma,
or choriocarcinoma (pure or mixed); age (years) >= 11 and < 25

- Site: testicular; stage: COG stage II-IV, AJCC stage II, III, International Germ
Cell Consensus Classification (IGCCC) good risk; histology: must contain at least
one of the following: yolk sac tumor, embryonal carcinoma, or choriocarcinoma
(pure or mixed); tumor markers: must be IGCCC good risk; post op: alpha-FP <
1,000 ng/mL, beta-HCG < 5,000 IU/mL and lactate dehydrogenase (LDH) < 3.0 x
normal; age (years) >= 11 and < 25

- Site: extragonadal; stage: COG stage II; histology: must contain at least one of
the following: yolk sac tumor, embryonal carcinoma, or choriocarcinoma (pure or
mixed) age (years) >= 11 and < 25

- Notes:

- IGCCC criteria only apply to SR2 patients with a testicular primary tumor

- Use post-op tumor marker levels to determine IGCCC risk group

- For the low risk stage I MGCT and the standard risk arms, components of yolk sac
tumor, embryonal carcinoma, or choriocarcinoma can be mixed with other forms of
GCT, such as seminoma or mature or immature teratoma; if yolk sac tumor is the
only malignant component present, then it must be deemed by the pathologist to be
greater than a ?microscopic component? of yolk sac tumor (i.e. > 5%)

- Patients must have a performance status corresponding to Eastern Cooperative Oncology
Group (ECOG) scores of 0, 1, 2 or 3; use Karnofsky for patients > 16 years of age and
Lansky for patients =< 16 years of age

- Organ function requirements apply ONLY to patients who will receive chemotherapy (SR1
and SR2 patients)

- Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70
mL/min/1.73 m^2

- A serum creatinine based on age/gender as follows: (mg/dL)

- 1 month to < 6 months male: 0.4 female: 0.4

- 6 months to < 1 year male: 0.5 female: 0.5

- 1 to < 2 years male: 0.6 female: 0.6

- 2 to < 6 years male: 0.8 female: 0.8

- 6 to < 10 years male: 1 female: 1

- 10 to < 13 years male: 1.2 female: 1.2

- 13 to < 16 years: male: 1.5 female: 1.4

- >= 16 years male: 1.7 female: 1.4

- Total bilirubin =< 1.5 x upper limit of normal (ULN) for age

- Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or
serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 2.5 x
upper limit of normal (ULN) for age (for the purpose of this study, the ULN for SGPT
is 45 U/L)

- No evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry > 94% if
there is clinical indication or determination; pulmonary function tests (PFTs) are not
required

- Eligibility criteria to participate in the pilot study of the AYA-Hears instrument
(patient reported outcomes [PROs] of ototoxicity) Note: participants in group 1 will
not receive AGCT1531 protocol-directed therapy; all other AYA-HEARS patients must be
enrolled on the AGCT1531 SR2 arm in order to participate

- >= 11 and < 25 years old at enrollment

- Able to fluently speak and read English

- Has received prior cisplatin- or carboplatin-based chemotherapy regimen for malignancy
including diagnoses other than germ cell tumor

- Followed for cancer or survivorship care at one of the following institutions:

- Dana Farber/Harvard Cancer Center

- Hospital for Sick Children

- Children?s Hospital of Eastern Ontario

- Oregon Health and Science University

- Seattle Children?s Hospital

- Yale University

- Has experienced prior or ongoing hearing impairment due to chemotherapy or
radiotherapy as defined by one of the following:

- Society of Pediatric Oncology (SIOP) grade 1 hearing loss

- Subjective (patient-reported) hearing difficulties

- Subjective (patient-reported) tinnitus
Minimum age
No limit
Maximum age
49 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Patients with any diagnoses not listed including:

- Stage I testicular cancer patients who have undergone primary RPLND
(retroperitoneal lymph node dissection)

- Pure dysgerminoma and pure seminoma

- Pure mature teratoma

- Pure immature teratoma COG stage I, grade I

- Pure immature teratoma COG stage I, grade 2,3 with alpha-fetoprotein (AFP) >=
1000 ng/mL

- Pure immature teratoma COG stage II - IV or FIGO stage IC to IV

- "Poor risk" GCT (age >= 11 years old and COG stage IV ovarian, COG stage III or
IV EG, or IGCCC intermediate or poor risk testicular), or

- Primary central nervous system (CNS) germ cell tumor

- Patients must have had no prior systemic therapy

- Patients must have had no prior radiation therapy with the exception of CNS
irradiation of brain metastases; (this exception only applies to SR1 patients; any
patients over age 11 with distant metastases to brain [stage IV disease] would be
considered poor risk and therefore not eligible for this trial)

- Patients with significant respiratory compromise due to either abdominal tumor
limiting diaphragmatic excursion or pulmonary metastases should not receive bleomycin
and are ineligible for the trial

- Female patients who are pregnant since fetal toxicities and teratogenic effects have
been noted for several of the study drugs; a pregnancy test is required for female
patients of childbearing potential; (this criteria applies ONLY to patients who will
receive chemotherapy [SR1 and SR2 patients])

- Lactating females who plan to breastfeed their infants; (this criteria applies ONLY to
patients who will receive chemotherapy [SR1 and SR2 patients])

- Sexually active patients of reproductive potential who have not agreed to use an
effective contraceptive method for the duration of their study participation; (this
criteria applies ONLY to patients who will receive chemotherapy [SR1 and SR2
patients])

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
John Hunter Children's Hospital - Hunter Regional Mail Centre
Recruitment hospital [2] 0 0
Sydney Children's Hospital - Randwick
Recruitment hospital [3] 0 0
The Children's Hospital at Westmead - Westmead
Recruitment hospital [4] 0 0
Lady Cilento Children's Hospital - South Brisbane
Recruitment hospital [5] 0 0
Monash Medical Center-Clayton Campus - Clayton
Recruitment hospital [6] 0 0
Royal Children's Hospital - Parkville
Recruitment hospital [7] 0 0
Princess Margaret Hospital for Children - Perth
Recruitment hospital [8] 0 0
Perth Children's Hospital - Perth
Recruitment postcode(s) [1] 0 0
2310 - Hunter Regional Mail Centre
Recruitment postcode(s) [2] 0 0
2031 - Randwick
Recruitment postcode(s) [3] 0 0
2145 - Westmead
Recruitment postcode(s) [4] 0 0
4101 - South Brisbane
Recruitment postcode(s) [5] 0 0
3168 - Clayton
Recruitment postcode(s) [6] 0 0
3052 - Parkville
Recruitment postcode(s) [7] 0 0
6008 - Perth
Recruitment postcode(s) [8] 0 0
6009 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
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United States of America
State/province [2] 0 0
Alaska
Country [3] 0 0
United States of America
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Arizona
Country [4] 0 0
United States of America
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Arkansas
Country [5] 0 0
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California
Country [6] 0 0
United States of America
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Colorado
Country [7] 0 0
United States of America
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Connecticut
Country [8] 0 0
United States of America
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Delaware
Country [9] 0 0
United States of America
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District of Columbia
Country [10] 0 0
United States of America
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Florida
Country [11] 0 0
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Georgia
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Hawaii
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Idaho
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Illinois
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Indiana
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Iowa
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Kentucky
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Louisiana
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Maine
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Maryland
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Massachusetts
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Michigan
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Minnesota
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Mississippi
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Missouri
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Montana
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Nebraska
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Nevada
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New Hampshire
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New Jersey
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New York
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United States of America
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North Carolina
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North Dakota
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Ohio
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Oklahoma
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Oregon
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Pennsylvania
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Rhode Island
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South Carolina
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South Dakota
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United States of America
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Tennessee
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Texas
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Utah
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Vermont
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Virginia
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Washington
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West Virginia
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United States of America
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Wisconsin
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Canada
State/province [49] 0 0
Alberta
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Canada
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Nova Scotia
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Canada
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Ontario
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Canada
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Quebec
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New Zealand
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Auckland
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New Zealand
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Christchurch
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Puerto Rico
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Caguas
Country [56] 0 0
Puerto Rico
State/province [56] 0 0
San Juan

Funding & Sponsors
Primary sponsor type
Other
Name
Children's Oncology Group
Address
Country
Other collaborator category [1] 0 0
Government body
Name [1] 0 0
National Cancer Institute (NCI)
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This phase III trial studies how well active surveillance, bleomycin, carboplatin, etoposide,
or cisplatin work in treating pediatric and adult patients with germ cell tumors. Active
surveillance may help doctors to monitor subjects with low risk germ cell tumors after their
tumor is removed. Drugs used in chemotherapy, such as bleomycin, carboplatin, etoposide, and
cisplatin, 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.
Trial website
https://clinicaltrials.gov/show/NCT03067181
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
A. L Frazier
Address 0 0
Children's Oncology Group
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No data has been provided for results reporting
Summary results
Not applicable