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

PHASE3RECRUITING

This phase III trial studies how well active surveillance help doctors to monitor subjects with low risk germ cell tumors for recurrence after their tumor is removed. When the germ cell tumor has spread outside of the organ in which it developed, it is considered metastatic. 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 metastatic standard risk germ cell tumors.

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Study details:

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 at time of recurrence if 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 undergo computed tomography (CT), magnetic resonance imaging (MRI), and/or chest x-ray as well as blood sample collection throughout the trial to monitor for response and recurrence. Patients may also undergo a tumor biopsy throughout the trial. 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.

Patients undergo CT, MRI, and/or chest x-ray as well as blood sample collection throughout the trial. Patients may also undergo a tumor biopsy throughout the trial. Patients undergo a pulmonary function test on study.

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, 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. Patients undergo CT, MRI, and/or chest x-ray as well as blood sample collection throughout the trial.

Patients may also undergo a tumor biopsy throughout the trial. Patients undergo a pulmonary function test on study. 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.

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Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

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: Patients 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: 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

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)

Patients enrolling on the standard risk arms must be medically fit to receive protocol treatment and with no contraindications to protocol treatment

>= 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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Eligibility

Age eligible for study : 0 and older

Healthy volunteers accepted : No

Gender eligible for study: All

Things to know

Study dates

Study start: 2017-05-25

Primary completion: 2027-06-30

Study completion finish: 2027-06-30

Study type

TREATMENT

Phase

PHASE3

Trial ID

NCT03067181

Intervention or treatment

OTHER: Best Practice

PROCEDURE: Biopsy

PROCEDURE: Biospecimen Collection

BIOLOGICAL: Bleomycin Sulfate

DRUG: Carboplatin

DRUG: Cisplatin

PROCEDURE: Computed Tomography

DRUG: Etoposide

PROCEDURE: Magnetic Resonance Imaging

OTHER: Pharmacogenomic Study

PROCEDURE: Pulmonary Function Test

OTHER: Quality-of-Life Assessment

OTHER: Questionnaire Administration

Conditions

• 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 Seminoma 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

Image related to Childhood Extracranial Germ Cell Tumor

Condition: Childhood Extracranial Germ Cell Tumor, Extragonadal Embryonal Carcinoma and more
OTHER: Best Practice and other drugs
Hunter Regional Mail Centre, New South Wales, Australia and more
Sponsor: Children's Oncology Group

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Find a site

Closest Location:

John Hunter Children's Hospital

Research sites nearby

Select from list below to view details:

John Hunter Children's Hospital
Hunter Regional Mail Centre, New South Wales, Australia
Sydney Children's Hospital
Randwick, New South Wales, Australia
The Children's Hospital at Westmead
Westmead, New South Wales, Australia
Queensland Children's Hospital
South Brisbane, Queensland, Australia

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Participant Group/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 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT, MRI, and/or chest x-ray as well as blood sample collection throughout the trial. Patients may also undergo a tumor biopsy throughout the trial. Patients undergo a pulmonary function test on study.	PROCEDURE: Biopsy Undergo a tumor biopsy
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. Patients undergo CT, MRI, and/or chest x-ray as well as blood sample collection throughout the trial. Patients may also undergo a tumor biopsy throughout the trial. Patients undergo a pulmonary function test on study.	PROCEDURE: Biopsy Undergo a tumor biopsy
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. Patients undergo CT, MRI, and/or chest x-ray as well as blood sample collection throughout the trial. Patients may also undergo a tumor biopsy throughout the trial. Patients undergo a pulmonary function test on study.	PROCEDURE: Biopsy Undergo a tumor biopsy
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. Patients undergo CT, MRI, and/or chest x-ray as well as blood sample collection throughout the trial. Patients may also undergo a tumor biopsy throughout the trial. Patients undergo a pulmonary function test on study.	PROCEDURE: Biopsy Undergo a tumor biopsy
EXPERIMENTAL: Low-Risk (observation) Patients with low-risk stage I grade 2, 3 ovarian immature teratoma or stage I non-seminoma or seminoma MGCTs 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 undergo CT, MRI, and/or chest x-ray as well as blood sample collection throughout the trial. Patients may also undergo a tumor biopsy throughout the trial.	OTHER: Best Practice Undergo observation

What is the study measuring?

Primary outcome

Primary Outcome Measure	Primary Outcome Description	Primary Outcome Time Frame
Overall survival	The time from study entry to the date of death, or date of last contact and ascertained as alive, whichever comes first.	Two years post enrollment
Event-free survival	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.	Two years post enrollment

Secondary outcome

Secondary Outcome Measure	Secondary Outcome Description	Secondary Outcome Time Frame
Proportion of participants with hearing loss	The hearing loss is evaluated according to the International Society of Pediatric Oncology criteria.	8 weeks after the last dose of platin therapy
Number of participants by understanding score category in the Adolescents and Young Adults-Hearing Screen	Understanding score will be rated on a 5-point Likert scale ranging from 0 = completely incorrect to 4 = completely correct.	Baseline

Frequently Asked Questions

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References

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