Accelerated or Standard BEP Chemotherapy in Treating Patients with Intermediate or Poor-Risk Metastatic Germ Cell Tumors
Germ Cell Tumor
11 - 45 Years, Male and Female
This phase III trial compares the effect of an accelerated schedule of bleomycin sulfate, etoposide phosphate, and cisplatin (BEP) chemotherapy to the standard schedule of BEP chemotherapy for the treatment of patients with intermediate or poor-risk germ cell tumors that have spread to other places in the body (metastatic). Drugs used in chemotherapy, such as bleomycin sulfate, etoposide phosphate, 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. Giving BEP chemotherapy on a faster, or “accelerated” schedule may work better with fewer side effects in treating patients with intermediate or poor-risk metastatic germ cell tumors compared to the standard schedule.
I. To compare the two treatment arms with respect to progression-free survival (disease progression or death).
I. To compare the two treatment arms with respect to:
Ia. Response following treatment completion (protocol-specific response criteria).
Ib. Adverse events (worst grade according to National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version [v]4.03).
Ic. Health-related quality of life (summary scales from Quality of Life Questionnaire [QLQ]-C30 & -Testicular Cancer [TC]-26).
Id. Treatment preference (proportion preferring each treatment arm).
Ie. Delivered dose-intensity of chemotherapy (relative to standard BEP).
If. Overall survival (death from any cause).
I. Determine associations between biomarkers to be specified and their correlations with clinical outcomes.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM A: Patients receive bleomycin sulfate intravenously (IV) over 10 minutes on days 1, 8, and 15 or 2, 9, and 16, etoposide phosphate IV over 1-2 hours once daily (QD) on days 1-5, cisplatin IV over 1-3 hours QD on days 1-5, and pegfilgrastim subcutaneously (SC) on day 6 or filgrastim for a minimum of 5 days until post-nadir absolute neutrophil count >= 1.0 x 10^9/L. Cycles repeat every 21 days for 12 weeks in the absence of disease progression or unacceptable toxicity. Patients receiving fewer than 8 doses of bleomycin sulfate due to pulmonary toxicity receive ifosfamide IV, mesna IV, etoposide phosphate IV, and cisplatin IV on days 1-5 and pegfilgrastim SC on day 6. Cycles repeat every 21 days for 12 weeks in the absence of disease progression or unacceptable toxicity.
ARM B: Patients receive bleomycin sulfate IV over 10 minutes on days 1 and 8 or 2 and 9, etoposide phosphate IV over 1-2 hours QD on days 1-5, cisplatin IV over 1-3 hours QD on days 1-5, and pegfilgrastim SC on day 6 or filgrastim for a minimum of 5 days until post-nadir absolute neutrophil count >= 1.0 x 10^9/L. Cycles repeat every 14 days for 12 weeks in the absence of disease progression or unacceptable toxicity. Patients receiving fewer than 8 doses of bleomycin sulfate due to pulmonary toxicity receive ifosfamide IV, mesna IV, etoposide phosphate IV, and cisplatin IV on days 1-5 and pegfilgrastim SC on day 6. Cycles repeat every 21 days for 12 weeks in the absence of disease progression or unacceptable toxicity. After 12 weeks, patients then receive bleomycin sulfate IV over 60 minutes weekly for 4 doses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 9, 12, 15, 18, 21, 24, 30, 36, 42, 48, 54, and 60 months, annually until disease progression, and then every 6 months after disease progression.
- Histologically or cytologically confirmed germ cell tumor (non-seminoma or seminoma); or exceptionally raised tumor markers (alpha-fetoprotein [AFP] >= 1000 ng/mL and/or human chorionic gonadotropin [HCG] >= 5000 IU/L) without histologic or cytologic confirmation in the rare case where pattern of metastases consistent with germ cell tumor (GCT), high tumor burden, and a need to start therapy urgently
- Primary arising in testis, ovary, retro-peritoneum, or mediastinum
- Metastatic disease or non-testicular primary
- Intermediate or poor prognosis as defined by International Germ Cell Cancer Consensus Classification (IGCCC) classification (modified with different lactate dehydrogenase [LDH] criteria for intermediate risk non-seminoma, and inclusion of ovarian primaries); see below
* Primary site: Testis or retro-peritoneum or mediastinum
** Histology: Non-seminoma
*** Prognostic category: Intermediate
**** Clinical Factors: Testes/retroperitoneal primary and no liver, bone, brain or other non-pulmonary visceral metastases and intermediate markers – any of:
***** AFP >= 1000 ng/mL and =< 10 000 ng/mL
***** HCG >= 5000 IU/L and =< 50 000 IU/L
***** LDH >= 3.0 x upper limit of normal (ULN) and =< 10 x ULN
*** Prognostic category: Poor
**** Clinical Factors: Mediastinal primary or liver, bone, brain or other non-pulmonary visceral metastases or poor markers – any of:
***** AFP > 10 000 ng/mL or
***** HCG > 50 000 IU/L or
***** LDH > 10 x ULN
** Histology: Seminoma
*** Prognostic category: Intermediate
**** Clinical factors: Any primary site and liver, bone, brain or other non-pulmonary visceral metastases and normal AFP, any HCG, any LDH
* Primary site: Ovary
** Histology: Malignant germ cell tumour histology (any of yolk sac, choriocarcinoma, embryonal carcinoma, mixed malignant GCT)
*** Prognostic category: Federation of Gynecology and Obstetrics (FIGO)/Children's Oncology Group (COG) stage IV
**** Distant metastases involving liver/spleen parenchyma and/or extra-abdominal organs (including but not limited to inguinal lymph nodes and lymph nodes outside abdominal cavity, lungs, bone, brain) and/or pleural effusion with positive cytology
- Absolute neutrophil count (ANC) >= 1.0 x 10^9/L
- Platelet count >= 100 x 10^9/L
- Bilirubin must be =< 1.5 x ULN, except participants with Gilbert’s syndrome where bilirubin must be =< 2.0 x ULN
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) must be =< 2.5 x ULN, except if the elevations are due to hepatic metastases, in which case ALT and AST must be =< 5 x ULN
- Estimated creatinine clearance of >= 60 ml/min according to the Cockcroft-Gault formula, unless calculated to be < 60 ml/min or borderline in which case glomerular filtration rate (GFR) should be formally measured, e.g. with edetic acid (EDTA) scan
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, 2, or 3
- Study treatment both planned and able to start within 14 days of randomization
- Willing and able to comply with all study requirements, including treatment, timing and nature of required assessments
- Able to provide signed, written informed consent
Treatment Sites in Georgia
1405 Clifton Road NE
Atlanta, GA 30322
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