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Active Surveillance, Bleomycin, Carboplatin, Etoposide, or Cisplatin in Treating Pediatric and Adult Patients With Germ Cell Tumors

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ClinicalTrials.gov Identifier: NCT03067181
Recruitment Status : Recruiting
First Posted : March 1, 2017
Last Update Posted : November 18, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group

Tracking Information
First Submitted Date  ICMJE February 14, 2017
First Posted Date  ICMJE March 1, 2017
Last Update Posted Date November 18, 2019
Actual Study Start Date  ICMJE May 8, 2017
Estimated Primary Completion Date June 30, 2027   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 14, 2019)
  • Overall survival [ Time Frame: Two years post enrollment ]
    The time from study entry to the date of death, or date of last contact and ascertained as alive, whichever comes first.
  • Event-free survival [ Time Frame: Two years post enrollment ]
    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.
Original Primary Outcome Measures  ICMJE
 (submitted: February 23, 2017)
  • EFS [ Time Frame: 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 ]
  • Overall survival (OS) [ Time Frame: 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 ]
    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 OS.
Change History Complete list of historical versions of study NCT03067181 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 14, 2019)
  • Percentage of participants with hearing loss [ Time Frame: 4 weeks after the last dose of platin therapy ]
    The hearing loss is evaluated according to the International Society of Pediatric Oncology criteria.
  • Number of participants by understanding score category in the Adolescents and Young Adults-Hearing Screen [ Time Frame: Baseline ]
    Understanding score will be rated on a 5-point Likert scale ranging from 0 = completely incorrect to 4 = completely correct.
Original Secondary Outcome Measures  ICMJE
 (submitted: February 23, 2017)
  • Content validity and understandability of AYA-Hearing Screen assessed by questionnaire [ Time Frame: Baseline ]
  • Incidence of ototoxicity [ Time Frame: 4 weeks after the last dose of platin therapy ]
    Will compare the proportion of patients who demonstrate hearing loss according to the International Society of Pediatric Oncology criteria.
  • Novel genetic variants associated with an increased risk of platinum-associated ototoxicity as determined by standard audiology [ Time Frame: Up to 10 years ]
    For each candidate gene, will perform an exact two-sided test for the equality of binomial proportions for the event - patient has the candidate gene. The two groups compared will be defined by the presence of SHL. Will use the Bonferroni correction to control experiment-wise error and designate the result as significant if the observed p-value is less than or equal to 0.0025.
  • Utility of the 4-miRNA panel as markers diagnostic of MGCTs [ Time Frame: Up to 10 years ]
    Will use categorical data methods and estimate the probability of demonstrating an elevated miRNA value as the proportion of patients who have the particular miRNA elevated.
  • Utility of the 4-miRNA panel as markers diagnostic of MGCTs [ Time Frame: Up to 10 years ]
    Will compare the diagnostic sensitivity of serum markers, particularly elevated alpha-fetoprotein, to that of elevated microRNA for each of the microRNAs, as well as the characteristic any microRNA elevated. Will perform McNemar's test. The result for each serum evaluation (elevated or not elevated) for each sample on which both serum marker and microRNA evaluation are obtained will be cross tabulated and the p-value associated with McNemar's test calculated. A p-value of 0.05 or less will be considered evidence of differential sensitivity.
Current Other Pre-specified Outcome Measures
 (submitted: November 14, 2019)
  • Event-free survival (EFS) for participants with and without tumor marker decline [ Time Frame: Up to 2 years ]
    Tumor marker decline is coded as yes vs no. EFS for participants with and without tumor marker decline will be reported separately.
  • Percentage of participants with self-reported peripheral neuropathy [ Time Frame: Up to 12 months ]
    Percentage of participants with self-reported peripheral neuropathy will be reported for carboplatin group and cisplatin group separately.
  • Percentage of participants with hearing loss [ Time Frame: Baseline ]
    Hearing loss is measured by audiometry and on the AYA-HEARS instrument.
Original Other Pre-specified Outcome Measures
 (submitted: February 23, 2017)
  • Activation of protein signaling pathway [ Time Frame: Up to 10 years ]
    Will assess the relationship between pathway activation, including EGFR, MAP Kinase and P3K and risk for disease progression. Tumor materials will be evaluated for the activation of specific pathways, including the three mentioned above. The effect of pathway activation, coded as yes vs. no, on the cause-specific hazard of EFS component disease progression will be estimated by relative risk regression considering other EFS events as censoring events. Will use the Benjamini and Hochberg procedure to control the false discovery rate.
  • Binomial data [ Time Frame: Up to 10 years ]
    Will use repeated measures binomial data as the initial approach to investigating this exploratory aim. Each biomarker will be examined individually. The predictor variables will be the measured value of particular novel biomarker and randomized treatment regimen. The response variable will be the occurrence of grade 3 or higher nephrotoxicity during the next treatment cycle. Will use logistic regression with a shared random frailty for outcomes for the same individual, when the subject's biomarkers are evaluated more than once during protocol therapy and the particular toxicity type is revers
  • Incidence of kidney dysfunction [ Time Frame: 12-16 weeks after the last dose of platin therapy ]
    Two patient characteristics will be used to measure kidney dysfunction: (1) the presence of Grade 1 or greater elevation of serum creatinine; and a second measure that is more sensitive for damage to the renal endothelium (2) albuminuria.
  • Incidence of self-reported peripheral neuropathy assessed by the 11-item Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity scale [ Time Frame: Up to 12 months ]
    Will compare the characteristics obtained at the start of chemotherapy of patients from the relevant groups who contribute to the patient reported outcome analyses with those who do not to investigate whether the measured group may not be representative of the study population. Will also conduct other sensitivity analysis as appropriate to assess the effects of missing data on the analysis for this aim.
  • Incidence of self-reported peripheral neuropathy assessed by the 11-item Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity scale [ Time Frame: Up to 12 months ]
    Will compare self-reported peripheral neuropathy and other patient-reported outcomes between children, adolescents and young adults with standard risk germ cell tumors treated with carboplatin-based chemotherapy as compared to cisplatin based chemotherapy.
  • Prognostic effects of the marker defined by microRNA signature present or high values of alpha-fetoprotein or beta-HCG [ Time Frame: Up to 10 years ]
    Will be assessed using a proportional approach. EFS from time of enrollment will be used for markers that are obtained at enrollment. EFS post complete evaluation of marker decline will be used for markers where the characteristic is the change in a putative marker.
  • Prognostic significance of the 4-miRNA panel [ Time Frame: Up to 10 years ]
    Will be assessed using time-dependent covariate analysis.
 
Descriptive Information
Brief Title  ICMJE Active Surveillance, Bleomycin, Carboplatin, Etoposide, or Cisplatin in Treating Pediatric and Adult Patients With Germ Cell Tumors
Official Title  ICMJE 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
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.
Detailed Description

PRIMARY OBJECTIVES:

I. To evaluate whether a strategy of complete surgical resection followed by surveillance can maintain an overall survival rate of at least 95.7% at two years for pediatric, adolescent and adult patients (ages 0 to < 50 years) with stage I (low risk) malignant germ cell tumors, and at least 95% for patients with ovarian pure immature teratoma.

II. To compare the event-free survival of a carboplatin versus (vs.) cisplatin-based regimen in the treatment of pediatric, adolescent and young adult patients with standard risk germ cell tumors.

IIa. To compare the event free survival (EFS) of a carboplatin-based regimen (carboplatin [C] etoposide [E] bleomycin [b]) vs. a cisplatin-based regimen (cisplatin [P]Eb) in children (less than 11 years in age) with standard risk germ cell tumors (GCT).

IIb. To compare the EFS of a carboplatin-based regimen (BEC) vs. a cisplatin-based regimen (BEP) in adolescents and young adults (ages 11 - < 25 years) with standard risk GCT.

SECONDARY OBJECTIVES:

I. To compare the incidence of ototoxicity in children, adolescents and young adults with standard risk germ cell tumors treated with carboplatin-based chemotherapy as compared to cisplatin-based chemotherapy.

II. To refine and validate a novel patient-reported measure of hearing outcomes for children, adolescents and young adults with standard risk germ cell tumors.

EXPLORATORY OBJECTIVES:

I. To prospectively determine the correlation of tumor marker decline (alpha-fetoprotein [FP] and beta-human chorionic gonadotropin [HCG]) with clinical outcome in low and standard risk germ cell tumor patients.

II. To compare self-reported peripheral neuropathy and other patient-reported outcomes between children, adolescents and young adults with standard risk germ cell tumors treated with carboplatin-based chemotherapy as compared to cisplatin based chemotherapy.

III. Assess the relationship between hearing loss as measured by audiometry with the effects of tinnitus as assessed on the Adolescent and Young Adult Hearing Screening (AYA-HEARS) instrument.

OUTLINE:

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

Patients with standard risk 1 are randomized into 1 of 2 arms.

ARM I (CEb): Patients receive bleomycin intravenously (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 cycles in the absence of disease progression or unacceptable toxicity.

ARM II (PEb): 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 cycles in the absence of disease progression or unacceptable toxicity.

Patients with standard risk 2 are randomized into 1 of 2 arms.

ARM III (BEC): 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 cycles in the absence of disease progression or unacceptable toxicity.

ARM IV (BEP): Patients receive bleomycin IV over 10 minutes on days 1, 8, 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 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up monthly to 12 months, every 2 months to 24 months, every 6 months for years 3-5, and then annually for up to 10 years.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Childhood Extracranial Germ Cell Tumor
  • Extragonadal Embryonal Carcinoma
  • Germ Cell Tumor
  • Malignant Germ Cell Tumor
  • Malignant Ovarian Teratoma
  • Stage I Ovarian Choriocarcinoma
  • Stage I Ovarian Embryonal Carcinoma AJCC v6 and v7
  • Stage I Ovarian Teratoma AJCC v6 and v7
  • Stage I Ovarian Yolk Sac Tumor AJCC v6 and v7
  • Stage I Testicular Choriocarcinoma AJCC v6 and v7
  • Stage I Testicular Embryonal Carcinoma AJCC v6 and v7
  • Stage I Testicular Yolk Sac Tumor AJCC v6 and v7
  • Stage II Ovarian Choriocarcinoma
  • Stage II Ovarian Embryonal Carcinoma AJCC v6 and v7
  • Stage II Ovarian Yolk Sac Tumor AJCC v6 and v7
  • Stage II Testicular Choriocarcinoma AJCC v6 and v7
  • Stage II Testicular Embryonal Carcinoma AJCC v6 and v7
  • Stage II Testicular Yolk Sac Tumor AJCC v6 and v7
  • Stage III Ovarian Choriocarcinoma
  • Stage III Ovarian Embryonal Carcinoma AJCC v6 and v7
  • Stage III Ovarian Yolk Sac Tumor AJCC v6 and v7
  • Stage III Testicular Choriocarcinoma AJCC v6 and v7
  • Stage III Testicular Embryonal Carcinoma AJCC v6 and v7
  • Stage III Testicular Yolk Sac Tumor AJCC v6 and v7
  • Stage IV Ovarian Choriocarcinoma
  • Stage IV Ovarian Embryonal Carcinoma AJCC v6 and v7
  • Stage IV Ovarian Yolk Sac Tumor AJCC v6 and v7
  • Testicular Mixed Choriocarcinoma and Embryonal Carcinoma
  • Testicular Mixed Choriocarcinoma and Teratoma
  • Testicular Mixed Choriocarcinoma and Yolk Sac Tumor
Intervention  ICMJE
  • Other: Best Practice
    Undergo observation
    Other Names:
    • standard of care
    • standard therapy
  • Drug: Bleomycin
    Given IV
    Other Names:
    • BLEO
    • BLM
  • Biological: Bleomycin Sulfate
    Given IV
    Other Names:
    • Blanoxan
    • BleMomycine
    • Blenoxane
    • Bleo-cell
    • Bleo-S
    • Bleocin
    • Bleolem
    • Bleomycin Sulfas
    • Bleomycin Sulphate
    • Bleomycini Sulfas
    • Blexane
    • Oil Bleo
  • 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: Cisplatin
    Given IV
    Other Names:
    • Abiplatin
    • Blastolem
    • Briplatin
    • CDDP
    • Cis-diammine-dichloroplatinum
    • Cis-diamminedichloridoplatinum
    • Cis-diamminedichloro Platinum (II)
    • Cis-diamminedichloroplatinum
    • Cis-dichloroammine Platinum (II)
    • Cis-platinous Diamine Dichloride
    • Cis-platinum
    • Cis-platinum II
    • Cis-platinum II Diamine Dichloride
    • Cismaplat
    • Cisplatina
    • Cisplatinum
    • Cisplatyl
    • Citoplatino
    • Citosin
    • Cysplatyna
    • DDP
    • Lederplatin
    • Metaplatin
    • Neoplatin
    • Peyrone''s Chloride
    • Peyrone''s Salt
    • Placis
    • Plastistil
    • Platamine
    • Platiblastin
    • Platiblastin-S
    • Platinex
    • Platinol
    • Platinol- AQ
    • Platinol-AQ
    • Platinol-AQ VHA Plus
    • Platinoxan
    • Platinum
    • Platinum Diamminodichloride
    • Platiran
    • Platistin
    • Platosin
  • 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: Etoposide Phosphate
    Given IV
    Other Name: Etopophos
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Other: Pharmacogenomic Study
    Correlative studies
    Other Name: PHARMACOGENOMIC
  • Other: Quality-of-Life Assessment
    Ancillary studies
    Other Name: Quality of Life Assessment
  • Other: Questionnaire Administration
    Ancillary studies
Study Arms  ICMJE
  • 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 cycles in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Drug: Bleomycin
    • Biological: Bleomycin Sulfate
    • Drug: Carboplatin
    • Drug: Etoposide
    • Drug: Etoposide Phosphate
    • Other: Laboratory Biomarker Analysis
    • Other: Pharmacogenomic Study
    • Other: Quality-of-Life Assessment
    • Other: Questionnaire Administration
  • 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 cycles in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Drug: Bleomycin
    • Biological: Bleomycin Sulfate
    • Drug: Cisplatin
    • Drug: Etoposide
    • Drug: Etoposide Phosphate
    • Other: Laboratory Biomarker Analysis
    • Other: Pharmacogenomic Study
    • Other: Quality-of-Life Assessment
    • Other: Questionnaire Administration
  • 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 cycles in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Drug: Bleomycin
    • Biological: Bleomycin Sulfate
    • Drug: Carboplatin
    • Drug: Etoposide
    • Drug: Etoposide Phosphate
    • Other: Laboratory Biomarker Analysis
    • Other: Pharmacogenomic Study
    • Other: Quality-of-Life Assessment
    • Other: Questionnaire Administration
  • 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 cycles in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Drug: Bleomycin
    • Biological: Bleomycin Sulfate
    • Drug: Cisplatin
    • Drug: Etoposide
    • Drug: Etoposide Phosphate
    • Other: Laboratory Biomarker Analysis
    • Other: Pharmacogenomic Study
    • Other: Quality-of-Life Assessment
    • Other: Questionnaire Administration
  • 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.
    Interventions:
    • Other: Best Practice
    • Other: Laboratory Biomarker Analysis
    • Other: Pharmacogenomic Study
    • Other: Quality-of-Life Assessment
    • Other: Questionnaire Administration
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 23, 2017)
1680
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 30, 2027
Estimated Primary Completion Date June 30, 2027   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 72 hours 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:

    • Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
    • 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

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 for the current cancer diagnosis
  • 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])
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 49 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE Australia,   Canada,   New Zealand,   Puerto Rico,   Saudi Arabia,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03067181
Other Study ID Numbers  ICMJE AGCT1531
NCI-2017-00178 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
AGCT1531
AGCT1531 ( Other Identifier: Childrens Oncology Group )
AGCT1531 ( Other Identifier: CTEP )
U10CA180886 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Children's Oncology Group
Study Sponsor  ICMJE Children's Oncology Group
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: A. L Frazier Children's Oncology Group
PRS Account Children's Oncology Group
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP