Active Surveillance for Low Risk and Trial of Carboplatin vs. Cisplatin for Standard Risk Patients with Germ Cell Tumors

What is the Purpose of this Study?

This study focuses on patients who have been diagnosed with a germ cell tumor (GCT). The “germ cell” is a cell that will become either the egg or the sperm. A germ cell tumor is a type of cancer that occurs in the ovaries (for females), the testes (for males), or rarely in other parts of the body (usually in the midline). Approved treatment for standard-risk germ cell tumors includes the chemotherapy drugs cisplatin, bleomycin and etoposide. Cisplatin has been known to cause long term side effects. Researchers aim to determine whether it is possible to decrease the side effects of chemotherapy treatment by replacing cisplatin with another chemotherapy drug called carboplatin. Patients will still receive the other two drugs (bleomycin and etoposide). The goal of the study is to compare the effects of carboplatin with cisplatin on individuals with standard-risk germ cell tumors in order to determine which is more effective.

Participants will be randomly assigned to one of two treatment groups. The first group will receive bleomycin, etoposide, and carboplatin (experimental). The second group will receive bleomycin, etoposide, and cisplatin (standard). Participants in both groups will receive supportive therapy to help with the side effects of treatment (and surgery if it is required).

Eligibility

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

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)
Adequate renal function defined as:
Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 (within 7 days prior to enrollment) OR
A serum creatinine based on age/gender as follows (within 7 days prior to enrollment): (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 (within 7 days prior to enrollment)
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) (within 7 days prior to enrollment)
Peripheral absolute neutrophil count (ANC) >= 1,000/mm^3 (within 7 days prior to enrollment) AND
Platelet count >= 100,000/mm^3 (within 7 days prior to enrollment)
Patients enrolling on the standard risk arms must be medically fit to receive protocol treatment and with no contraindications to protocol treatment
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
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
Germ cell tumor with somatic malignant transformation
Spermatocytic seminoma
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, pre-existing co-morbid respiratory disease that contraindicate the use of bleomycin are ineligible for the standard risk arms of 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])

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Where can I participate?

Cedars-Sinai Cancer at SOCC

More about this Clinical Trial

What is the full name of this clinical trial?

AGCT1531: 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 ^

Study Details

Disease Type/Condition

Other Female Genital, Other Male Genital, Ovary, Soft Tissue

Principal Investigator

Mascarenhas, Leo

Co-Investigators

Fataneh Majlessipour, Nicole Baca

Age Group

Both

Phase

III

IRB Number

STUDY00000436

ClinicalTrials.gov ID

NCT03067181

Key Eligibility

ClinicalTrials.gov

How do I learn more about this study?

clinicaltrials@cshs.org