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 Tumours
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 tumours. Active surveillance may help doctors to monitor subjects with low risk germ cell tumours after their tumour is removed. Drugs used in chemotherapy, such as bleomycin, carboplatin, etoposide, and cisplatin, work in different ways to stop the growth of tumour 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 tumours.
Trial Description
Primary Outcome:
- Overall survival
- Event-free survival
Secondary Outcome:
- Proportion of participants with hearing loss
- Number of participants by understanding score category in the Adolescents and Young Adults-Hearing Screen
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 tumours, 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 tumours.
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 tumours (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 tumours 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 tumours.
EXPLORATORY OBJECTIVES:
I. To prospectively determine the correlation of tumour marker decline (alpha-fetoprotein [FP] and beta-human chorionic gonadotropin [HCG]) with clinical outcome in low and standard risk germ cell tumour patients.
II. To compare self-reported peripheral neuropathy and other patient-reported outcomes between children, adolescents and young adults with standard risk germ cell tumours 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 tumours (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 undergo computed tomography (CT), magnetic resonance imaging (MRI), and/or chest x-ray as well as blood sample collection throughout the trial. Patients may also undergo a tumour 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 tumour 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 undergo CT, MRI, and/or chest x-ray as well as blood sample collection throughout the trial. Patients may also undergo a tumour biopsy throughout the trial. Patients undergo a pulmonary function test on study.
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. Patients undergo CT, MRI, and/or chest x-ray as well as blood sample collection throughout the trial. Patients may also undergo a tumour biopsy throughout the trial. Patients undergo a pulmonary function test on study.
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. Patients undergo CT, MRI, and/or chest x-ray as well as blood sample collection throughout the trial. Patients may also undergo a tumour 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.
View this trial on ClinicalTrials.gov
