Georgia's Online Cancer Information Center

Find A Clinical Trial

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

Status
Active
Cancer Type
Germ Cell Tumor
Testicular Cancer
Trial Phase
Phase III
Eligibility
0 Years and older, Male and Female
Study Type
Treatment
NCT ID
NCT03067181
Protocol IDs
AGCT1531 (primary)
AGCT1531
NCI-2017-00178
AGCT1531
Study Sponsor
Children's Oncology Group

Summary

This phase III trial studies how well active surveillance, bleomycin, etoposide, carboplatin 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. The trial studies whether carboplatin or cisplatin is the preferred chemotherapy to use in treating germ cell tumors.

Objectives

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.

Eligibility

  1. 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])
  2. Standard risk 1: Patient must be < 11 years of age at enrollment
  3. Standard risk 2: Patients must be >= 11 and < 25 years of age at enrollment
  4. 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
  5. 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
  6. 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
  7. 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
  8. 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
  9. 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
  10. 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
  11. 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
  12. Organ function requirements apply ONLY to patients who will receive chemotherapy (SR1 and SR2 patients)
  13. Adequate renal function defined as:
  14. Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 OR
  15. 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
  16. Total bilirubin =< 1.5 x upper limit of normal (ULN) for age
  17. 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)
  18. Peripheral absolute neutrophil count (ANC) >= 1,000/mm^3 AND
  19. Platelet count >= 100,000/mm^3
  20. Patients enrolling on the standard risk arms must be medically fit to receive protocol treatment and with no contraindications to protocol treatment
  21. 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
  22. >= 11 and < 25 years old at enrollment
  23. Able to fluently speak and read English
  24. Has received prior cisplatin- or carboplatin-based chemotherapy regimen for malignancy including diagnoses other than germ cell tumor
  25. 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

Treatment Sites in Georgia

Atrium Health Navicent


Oncology Research, Atrium Health Navicent
777 Hemlock Street, MSC 123
(PACC 800 1st St, Ste 250)
Macon, GA 31201
4786332152
www.Atriumhealth.org

Study Coordinator:
Oncology Research Nurse
4786332152

Doctors:

Sushmita Nair
Vishwas Sakhalkar
Kristi George, MD
Abigail Cruz, MD

Augusta University Medical Center


1120 15th Street
Augusta, GA 30912
706-721-4430
www.augustahealth.org

**Clinical trials are research studies that involve people. These studies test new ways to prevent, detect, diagnose, or treat diseases. People who take part in cancer clinical trials have an opportunity to contribute to scientists’ knowledge about cancer and to help in the development of improved cancer treatments. They also receive state-of-the-art care from cancer experts... Click here to learn more about clinical trials.
Georgia CORE

 

Advancing Cancer Care through Partnerships and Innovation

Georgia CORE is a statewide nonprofit that leverages partnerships and innovation to attract more clinical trials, increase research, and promote education and early detection to improve cancer care for Georgians in rural, urban, and suburban communities across the state.