ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03067181
Recruitment Status : Recruiting
First Posted : March 1, 2017
Last Update Posted : August 7, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group

Brief Summary:
This partially randomized 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.

Condition or disease Intervention/treatment Phase
Adult Germ Cell Tumor Childhood Extracranial Germ Cell Tumor Childhood Germ Cell Tumor Extragonadal Embryonal Carcinoma Grade 2 Immature Ovarian Teratoma Grade 3 Immature Ovarian Teratoma Malignant Germ Cell Tumor Stage I Ovarian Choriocarcinoma Stage I Ovarian Embryonal Carcinoma Stage I Ovarian Teratoma Stage I Ovarian Yolk Sac Tumor 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 Stage II Ovarian Yolk Sac Tumor 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 Stage III Ovarian Yolk Sac Tumor 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 Stage IV Ovarian Yolk Sac Tumor Testicular Mixed Choriocarcinoma and Embryonal Carcinoma Testicular Mixed Choriocarcinoma and Teratoma Testicular Mixed Choriocarcinoma and Yolk Sac Tumor Other: Best Practice Drug: Bleomycin Drug: Carboplatin Drug: Cisplatin Drug: Etoposide Other: Laboratory Biomarker Analysis Other: Pharmacogenomic Study Other: Quality-of-Life Assessment Other: Questionnaire Administration Phase 3

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1680 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : May 8, 2017
Estimated Primary Completion Date : December 31, 2022
Estimated Study Completion Date : December 31, 2022


Arm Intervention/treatment
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.
Drug: Bleomycin
Given IV
Other Names:
  • BLEO
  • BLM

Drug: Carboplatin
Given IV
Other Names:
  • Blastocarb
  • Carboplat
  • Carboplatin Hexal
  • Carboplatino
  • 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 16-213
  • VP-16
  • VP-16-213

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

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.
Drug: Bleomycin
Given IV
Other Names:
  • BLEO
  • BLM

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 16-213
  • VP-16
  • VP-16-213

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

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.
Drug: Bleomycin
Given IV
Other Names:
  • BLEO
  • BLM

Drug: Carboplatin
Given IV
Other Names:
  • Blastocarb
  • Carboplat
  • Carboplatin Hexal
  • Carboplatino
  • 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 16-213
  • VP-16
  • VP-16-213

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

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.
Drug: Bleomycin
Given IV
Other Names:
  • BLEO
  • BLM

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 16-213
  • VP-16
  • VP-16-213

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

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: Best Practice
Undergo observation
Other Names:
  • standard of care
  • standard therapy

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




Primary Outcome Measures :
  1. Overall survival [ 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 overall survival.

  2. Event-free survival [ 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 ]
    Will compare between a carboplatin-based regimen versus a cisplatin-based regimen.


Secondary Outcome Measures :
  1. 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.

  2. Content validity and understandability of Adolescents and Young Adults-Hearing Screen [ Time Frame: Baseline ]
    Will be assessed by questionnaire.

  3. Utility of the 4-micro ribonucleic acid panel as markers diagnostic of mediastinal germ cell tumors [ Time Frame: Up to 10 years ]
    Will use categorical data methods and estimate the probability of demonstrating an elevated micro ribonucleic acid value as the proportion of patients who have the particular micro ribonucleic acid elevated.

  4. Utility of the 4-micro ribonucleic acid panel as markers diagnostic of mediastinal germ cell tumors [ Time Frame: Up to 10 years ]
    Will compare the diagnostic sensitivity of serum markers, particularly elevated alpha-fetoprotein, to that of elevated micro ribonucleic acid for each of the micro ribonucleic acids, as well as the characteristic any micro ribonucleic acid 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 micro ribonucleic acid 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.

  5. 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 significant hearing loss. 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.


Other Outcome Measures:
  1. 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 versus no, on the cause-specific hazard of event-free survival component disease progression will be estimated by relative risk regression considering other event-free survival events as censoring events. Will use the Benjamini and Hochberg procedure to control the false discovery rate.

  2. Prognostic significance of the 4-micro ribonucleic acid panel [ Time Frame: Up to 10 years ]
    Will be assessed using time-dependent covariate analysis.

  3. Prognostic effects of the marker defined by micro ribonucleic acid signature present or high values of alpha-fetoprotein or beta-HCG [ Time Frame: Up to 10 years ]
    Will be assessed using a proportional approach. Event-free survival from time of enrollment will be used for markers that are obtained at enrollment. Event-free survival post complete evaluation of marker decline will be used for markers where the characteristic is the change in a putative marker.

  4. 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.

  5. 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.

  6. 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.

  7. 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 reversible.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   up to 49 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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, 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 and IB; 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: for IGCCC good risk: alpha-FP < 1,000 ng/mL, beta-HCG < 5,000 IU/mL and lactate dehydrogenase (LDH) < 1.5 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
  • Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2; use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age
  • 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 group 1 of the pilot study of the AYA-Hears instrument Note: participants in group 1 will not receive protocol-directed therapy
  • >= 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

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 with alpha-fetoprotein (AFP) >= 1000 ng/mL
    • Pure immature teratoma COG stage II - IV or FIGO stage IC to IV
    • Poor risk disease (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)
  • SR1 and SR2 patients:
  • Female patients who are pregnant; a pregnancy test is required for female patients of childbearing potential
  • Lactating females who plan to breastfeed their infants
  • Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03067181


  Show 436 Study Locations
Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
Investigators
Principal Investigator: A. Frazier Children's Oncology Group

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT03067181     History of Changes
Other Study ID Numbers: 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 )
First Posted: March 1, 2017    Key Record Dates
Last Update Posted: August 7, 2018
Last Verified: November 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Carcinoma
Neoplasms
Neoplasms, Germ Cell and Embryonal
Teratoma
Carcinoma, Embryonal
Endodermal Sinus Tumor
Choriocarcinoma
Ovarian Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Mesonephroma
Trophoblastic Neoplasms
Adenocarcinoma
Pregnancy Complications, Neoplastic
Pregnancy Complications
Endocrine Gland Neoplasms
Neoplasms by Site
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Etoposide phosphate
Cisplatin
Carboplatin
Etoposide
Bleomycin
Podophyllotoxin