Extragonadal Germ Cell Tumor, Teratoma, Testicular Germ Cell Tumor
Conditions
Keywords
stage II malignant testicular germ cell tumor, stage III malignant testicular germ cell tumor, testicular choriocarcinoma and embryonal carcinoma, testicular choriocarcinoma and teratoma, testicular choriocarcinoma and yolk sac tumor, testicular choriocarcinoma, testicular embryonal carcinoma and teratoma, testicular embryonal carcinoma and yolk sac tumor, testicular embryonal carcinoma, testicular yolk sac tumor and teratoma, testicular yolk sac tumor, stage II extragonadal non-seminomatous germ cell tumor, stage III extragonadal non-seminomatous germ cell tumor, testicular immature teratoma, testicular mature teratoma, adult teratoma
Brief summary
RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. PURPOSE: This randomized phase III trial is comparing two different combination chemotherapy regimens to see how well they work in treating patients with stage II or stage III non-seminomatous germ cell tumors.
Detailed description
OBJECTIVES: * Compare progression-free survival rates of patients with poor prognosis stage II or III non-seminomatous germ cell tumors with an unfavorable decrease of tumor markers after treatment with 1 course of bleomycin, etoposide, and cisplatin followed by subsequent treatment with 3 additional courses of bleomycin, etoposide, and cisplatin OR dose-dense sequential combination chemotherapy. * Compare overall survival of patients treated with these regimens. OUTLINE: This is a randomized, multicenter study. Patients receive 1 course of bleomycin, etoposide, and cisplatin (BEP). Patients with a favorable decrease of tumor markers after 1 course of BEP receive 3 additional courses of BEP. Patients with an unfavorable decrease of tumor markers after 1 course of BEP are randomized to 1 of 2 treatment arms. * Arm I: Patients receive 3 additional courses of BEP. * Arm II: Patients receive dose-dense sequential combination chemotherapy comprising cisplatin, etoposide, bleomycin, paclitaxel, oxaliplatin, and ifosfamide. PROJECTED ACCRUAL: A total of 260 patients will be accrued for this study.
Interventions
BIOLOGICALbleomycin sulfate
At least one course administered
DRUGcisplatin
At least one course administered
DRUGetoposide
At least one course administered
DRUGifosfamide
Given in a dose-dense sequential fashion
DRUGoxaliplatin
Given in a dose-dense sequential fashion
DRUGpaclitaxel
Given in a dose-dense sequential fashion
Sponsors
UNICANCER
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Phase 3 trial with direct individual benefit, randomized, open-label, multicenter, parallel groups
Eligibility
Sex/Gender
ALL
Age
16 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Diagnosis of non-seminomatous germ cell tumors (NSGCT) as evidenced by 1 of the following criteria: * Histologically confirmed NSGCT * Clinical evidence of disease AND high serum human chorionic gonadotropin (HCG) or alpha-fetoprotein (AFP) levels * Clinical stage II-III disease (disseminated disease) * Testicular, retroperitoneal, or mediastinal primary site * Poor prognosis disease, meeting 1 of the following criteria: * Mediastinal primary site * Non-pulmonary visceral metastases * One of the following lab values: * HCG \> 50,000 UI/L * AFP \> 10,000 ng/mL * Lactate dehydrogenase \> 10 times upper limit of normal (ULN) PATIENT CHARACTERISTICS: Age * Over 16 Performance status * Not specified Life expectancy * Not specified Hematopoietic * Absolute granulocyte count ≥ 1,500/mm\^3 * Platelet count ≥ 100,000/mm\^3 Hepatic * Bilirubin ≤ 1.5 times ULN Renal * Creatinine clearance \> 60 mL/min Other * No other prior malignancy except basal cell skin cancer * No HIV positivity PRIOR CONCURRENT THERAPY: Biologic therapy * Not specified Chemotherapy * No prior chemotherapy Endocrine therapy * Not specified Radiotherapy * Not specified Surgery * Not specified
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival Rate After 1 Course of Treatment | 3 years from randomization | Primary objective is to compare the progression-free survival of participants after 1 cycle of treatment, treated randomly by 3 additional cycles of BEP (Arm I) or by T-BEP-Oxaliplatin/cisplatin-ifosfamide-Bleomycin (Arm II). The median progression-free survival rate was defined as the median percentage of participants alive without disease progression after 1 course of treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | 3 years from randomization | To evaluated the overall survival in both groups in participants presenting fast and slow decrease in serum levels of tumor markers. The median overall survival was defined as the median percentage of participants alive after 1 course of treatment. |
Countries
France, Slovakia, United States
Participant flow
Pre-assignment details
Of the 263 patients registered 255 were evaluated for biomarker decrease after one cycle of BEP. Eight patients were not evaluated for biomarker decrease: 6 patients died early, 1 patient 1 withdrew consent and 1 patient was included by error. 1 patient was not covered by EC approval and excluded froma analysis. The 203 patients with unfavorable decrease in tumor biomarkers were randomized in Arm I (98 patients) or Arm II (105 patients).
Participants by arm
| Arm | Count |
|---|---|
| Arm I Patients receive 4 courses of bleomycin, etoposide, and cisplatin (BEP).
bleomycin sulfate: At least one course administered
cisplatin: At least one course administered
etoposide: At least one course administered | 98 |
| Arm II Patients receive 1 course of bleomycin, etoposide, and cisplatin (BEP). Patients then receive dose-dense sequential combination chemotherapy comprising cisplatin, etoposide, bleomycin, paclitaxel, oxaliplatin, and ifosfamide.
bleomycin sulfate: At least one course administered
cisplatin: At least one course administered
etoposide: At least one course administered
ifosfamide: Given in a dose-dense sequential fashion
oxaliplatin: Given in a dose-dense sequential fashion
paclitaxel: Given in a dose-dense sequential fashion | 105 |
| Total | 203 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 3 | 2 |
| Overall Study | treatment interruption | 4 | 10 |
| Overall Study | Withdrawal by Subject | 0 | 2 |
Baseline characteristics
| Characteristic | Arm I | Arm II | Total |
|---|---|---|---|
| Age, Continuous | 27 Years | 30 Years | 30 Years |
| Region of Enrollment France | 79 participants | 87 participants | 166 participants |
| Region of Enrollment Slovakia | 9 participants | 9 participants | 18 participants |
| Region of Enrollment United States | 10 participants | 9 participants | 19 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 98 Participants | 105 Participants | 203 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 61 / 98 | 66 / 105 |
| other Total, other adverse events | 98 / 98 | 105 / 105 |
| serious Total, serious adverse events | 37 / 98 | 58 / 105 |
Outcome results
Primary
Progression-free Survival Rate After 1 Course of Treatment
Primary objective is to compare the progression-free survival of participants after 1 cycle of treatment, treated randomly by 3 additional cycles of BEP (Arm I) or by T-BEP-Oxaliplatin/cisplatin-ifosfamide-Bleomycin (Arm II). The median progression-free survival rate was defined as the median percentage of participants alive without disease progression after 1 course of treatment.
Time frame: 3 years from randomization
Population: The primary endpoint for the study was the comparison of the PFS rates in the population of participants with a poor prognostic non-seminomatous germ cell tumors and with an unfavorable decrease in tumor biomarkers, randomized to either Unfav-BEP Control Arm (Arm I) or Unfav-Dose-Dense Arm (Arm II).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm I | Progression-free Survival Rate After 1 Course of Treatment | 48 percentage of participants |
| Arm II | Progression-free Survival Rate After 1 Course of Treatment | 59 percentage of participants |
Comparison: To detect an absolute difference of 20% in progression-free survival at 3-years between Arm I and Unfav-Dose-Dense Arm II (46% versus 66%) with the possibility that 80 events (progressive disease and death) may be observed during this period, a total of 196 participants, 98 per group needed to be included, with an additional 25% of patients for a total of 260 participants required.p-value: 0.0595% CI: [0.44, 1]Log Rank
Secondary
Overall Survival
To evaluated the overall survival in both groups in participants presenting fast and slow decrease in serum levels of tumor markers. The median overall survival was defined as the median percentage of participants alive after 1 course of treatment.
Time frame: 3 years from randomization
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm I | Overall Survival | 65 percentage of participants |
| Arm II | Overall Survival | 73 percentage of participants |
p-value: 0.3495% CI: [0.46, 1.31]Log Rank