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

  • STATUS
    Recruiting
  • End date
    Jun 30, 2027
  • participants needed
    2059
  • sponsor
    Children's Oncology Group
Updated on 2 August 2021
platelet count
cancer
beta-human chorionic gonadotropin
tumor markers
carcinoma
etoposide
human chorionic gonadotropin
neutrophil count
carboplatin
tumor cells
primary tumor
cancer chemotherapy
bleomycin
beta human chorionic gonadotropin
testicular
seminoma
teratoma
mg++
immature teratoma

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.

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 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 non-seminomatous 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.

IV. To evaluate the prognostic significance of serum micro ribonucleic acid (miRNA)s in stage I testicular cancer (seminoma and non-seminoma) patients by collecting clinical data and serum specimens for future analysis.

OUTLINE

Patients with low-risk stage I grade 2, 3 ovarian immature teratoma or stage I non-seminoma malignant germ cell tumors (MGCT)s undergo observation and can transfer to standard risk arm when eligibility criteria are met. Patients with stage I seminoma testicular MGCT undergo observation, and those with residual/recurrent disease are treated at the discretion of their physician.

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 every 2 months for 12 months, every 3-6 months to 24 months, every 6 months for years 3-5, and then annually for up to 10 years.

Details
Condition Germ cell tumor, Childhood Germ Cell Tumor, Adult Germ Cell Tumor, Childhood Extracranial Germ Cell Tumor, Extragonadal Embryonal Carcinoma, Grade 2 Immature Ovarian Teratoma, Grade 3 Immature Ovarian Teratoma, Stage I Ovarian Choriocarcinoma, Stage I Ovarian Embryonal Carcinoma, Stage I Ovarian Teratoma, Stage I Ovarian Yolk Sac Tumor, Stage I Testicular Choriocarcinoma, Stage I Testicular Embryonal Carcinoma, Stage I Testicular Yolk Sac Tumor, Stage II Ovarian Choriocarcinoma, Stage II Ovarian Embryonal Carcinoma, Stage II Ovarian Yolk Sac Tumor, Stage II Testicular Choriocarcinoma, Stage II Testicular Embryonal Carcinoma, Stage II Testicular Yolk Sac Tumor, Stage III Ovarian Choriocarcinoma, Stage III Ovarian Embryonal Carcinoma, Stage III Ovarian Yolk Sac Tumor, Stage III Testicular Choriocarcinoma, Stage III Testicular Embryonal Carcinoma, Stage III Testicular Yolk Sac Tumor, 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, 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 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 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, Germ Cell Tumors, Grade 2 Ovarian Teratoma, Malignant Ovarian Teratoma, 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 II Ovarian Embryonal Carcinoma AJCC v6 and v7, Stage II Ovarian Yolk Sac Tumor AJCC v6 and v7, Stage III Ovarian Embryonal Carcinoma AJCC v6 and v7, Stage III Ovarian Yolk Sac Tumor AJCC v6 and v7, Stage IV Ovarian Embryonal Carcinoma AJCC v6 and v7, Stage IV Ovarian Yolk Sac Tumor AJCC v6 and v7, Stage I Testicular Seminoma AJCC v6 and v7
Treatment laboratory biomarker analysis, questionnaire administration, cisplatin, quality-of-life assessment, etoposide, carboplatin, Bleomycin, Etoposide Phosphate, bleomycin sulfate, Best Practice, Pharmacogenomic Study
Clinical Study IdentifierNCT03067181
SponsorChildren's Oncology Group
Last Modified on2 August 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

There is no age limit for the low risk stratum (stage I ovarian immature teratoma and stage I non-seminoma or seminoma malignant GCT [all sites])
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
Patients enrolling on one of the low risk arms must be newly diagnosed with a stage I germ cell tumor; for the standard risk arms, patients must be newly diagnosed with metastatic germ cell tumor (stage II or higher); histologic confirmation of a primary extracranial germ cell tumor in any of the categories outlined below is required of all patients at enrollment except for those who were initially diagnosed with stage I non-seminoma malignant GCT and later recur during observation post surgery off study; for these patients, if elevated tumor markers rise to > 5 x upper limit of normal (ULN) on at least 2 measurements taken at least 1 week apart, a diagnostic biopsy is not required for 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 microscopic foci of yolk sac tumor), mixed immature and mature teratoma, (no pathological evidence of MGCT); tumor markers: alpha-FP =< 1,000 ng/mL, beta-HCG institutional normal; all ages
Low risk stage I non-seminoma MGCT; 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); all ages
Low risk stage I seminoma-MGCT; site: testicular; stage: COG stage I; AJCC testicular stage IA IB, and IS; histology: must contain at least one of the following: may contain immature/mature teratoma; may NOT contain yolk sac tumor, embryonal carcinoma, or choriocarcinoma; all ages
Standard risk 1 (SR1); site: ovarian, testicular, or extragonadal; stage: COG stage II-IV, FIGO stage IC, FIGO stage II-IV (International Germ Cell Consensus Classification [IGCCC] criteria DO NOT apply); histology: must contain at least one of the following: yolk sac tumor, embryonal carcinoma, or choriocarcinoma; 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; age (years) >= 11 and < 25
Site: testicular; stage: COG stage II-IV, AJCC stage II, III, IGCCC good risk; histology: must contain at least one of the following: yolk sac tumor, embryonal carcinoma, or choriocarcinoma; 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; 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
Stage 1 seminoma patients are not eligible for the standard risk arms of the study
For the low risk stage I non-seminoma 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
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)
month to < 6 months male: 0.4 female: 0.4
months to < 1 year male: 0.5 female: 0.5
to < 2 years male: 0.6 female: 0.6
to < 6 years male: 0.8 female: 0.8
to < 10 years male: 1 female: 1
to < 13 years male: 1.2 female: 1.2
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)
Peripheral absolute neutrophil count (ANC) >= 1,000/mm^3
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
Platelet count >= 100,000/mm^3
>= 11 and < 25 years old at enrollment
Patients enrolling on the standard risk arms must be medically fit to receive protocol treatment and with no contraindications to protocol treatment
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 mature teratoma
Pure immature teratoma COG stage I, grade I
Pure dysgerminoma
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)
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])
Germ cell tumor with somatic malignant transformation
Lactating females who plan to breastfeed their infants; (this criteria applies ONLY to patients who will receive chemotherapy [SR1 and SR2 patients])
Spermatocytic seminoma
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])
Patients with significant, pre-existing co-morbid respiratory disease that contraindicate the use of bleomycin, are ineligible for the standard risk arms of the trial
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