nct02375204

Eligibility

Inclusion Criterea

• Confirmation of GCT histology (both seminoma and nonseminoma) on pathologic review at the center of enrollment; tumor may have originated in any primary site * NOTE: in rare circumstances, patients will be allowed to enroll even if a pathologic diagnosis may not have been established; this would require a clinical situation consistent with the diagnosis of GCT (testicular, peritoneal, retroperitoneal or mediastinal mass, elevated tumor marker levels [HCG >= 500; AFP >= 500] and typical pattern of metastases)
• Must have evidence of progressive or recurrent GCT (measurable or non-measurable) following one line of cisplatin-based chemotherapy, defined as meeting at least one of the following criteria: * Tumor biopsy of new or growing or unresectable lesions demonstrating viable non-teratomatous GCT (enrollment on this study for adjuvant treatment after macroscopically complete resection of viable GCT is not allowed); in the event of an incomplete gross resection where viable GCT is found, patients will be considered eligible for the study * Consecutive elevated serum tumor markers (HCG or AFP) that are increasing; increase of an elevated lactate dehydrogenase (LDH) alone does not constitute progressive disease * Development of new or enlarging lesions in the setting of persistently elevated HCG or AFP, even if the HCG and AFP are not continuing to increase
• Must have received 3-6 cycles of cisplatin-based chemotherapy as part of first-line (initial) chemotherapy; prior cisplatin, vincristine, methotrexate, bleomycin, actinomycin D, cyclophosphamide, etoposide (POMBACE), carboplatin, bleomycin, vincristine, and cisplatin-bleomycin, etoposide, and cisplatin (CBOP-BEP), or methotrexate, actinomycin-D, etoposide, cisplatin, peg filgrastim (GAMEC) are allowed; Note: for patients requiring immediate treatment, 1 cycle of conventional-dose salvage chemotherapy is allowed (including TI or TIP); therefore, these patients may have received 7 prior cycles of chemotherapy; 6 cycles as part of first-line chemotherapy and 1 cycle of salvage conventional chemotherapy
• No more than one prior line of chemotherapy for GCT (other than the 1 cycle of salvage chemotherapy) * Definition of one line of chemotherapy: One line of therapy can in some cases consist of 2 different cisplatin-based treatment combinations, provided there is no disease progression between these two regimens; for example, a patient could have received 2 cycles of bleomycin, etoposide, and cisplatin (BEP) followed by 2 cycles of cisplatin, ifosfamide, and etoposide (VIP) if the switch from BEP to VIP was made due to pulmonary toxicity rather than disease progression; this would be considered 1 line of prior therapy; in addition, if a patient received 4 cycles of BEP and then underwent post-chemotherapy resection of residual tumor with findings of residual viable non-teratomatous GCT, and subsequently received 2 additional cycles of adjuvant chemotherapy (etoposide, cisplatin [EP] or an alternate regimen such as VIP) in the absence of disease progression, this would also be considered 1 regimen; however, if any change in therapy is prompted by tumor progression including rising tumor markers, this is considered to represent 2 lines of prior treatment * Prior treatment with carboplatin as adjuvant therapy is allowed, provided patients meet other eligibility criteria (e.g., the patient has also received 3-4 cycles of cisplatin-based chemotherapy) * Prior treatment with 1-2 cycles of BEP or EP as adjuvant chemotherapy for early stage GCT is allowed, provided the patient also received 3-4 cycles of BEP or EP again at relapse; patients treated with 3-4 cycles of VIP at relapse following 1-2 cycles of BEP/EP are not eligible as this would be considered more than 1 line of prior therapy
• No prior treatment with high-dose chemotherapy (defined as treatment utilizing stem cell rescue)
• No prior treatment with TIP with the exception when given as a bridge to treatment on protocol for patients with rapidly progressive disease who cannot wait to complete the eligibility screening process; only one cycle is allowed
• No concurrent treatment with other cytotoxic drugs or targeted therapies
• No radiation therapy (other than to the brain) within 14 days of day 1 of protocol chemotherapy except radiation to brain metastases, which must be completed 7 days prior to start of chemotherapy
• No previous chemotherapy within 16 days prior to enrollment except for bleomycin which cannot have been given within 5 days prior to enrollment
• Must have adequate recovery from prior surgery (e.g., healed scar, resumption of diet, etc.)
• Age >= 14 years (>= 18 years in Germany)
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
• Absolute neutrophil count (ANC) >= 1,500/mm^3
• Platelet count >= 100,000/mm^3
• Calculated (calc.) creatinine clearance >= 50 mL/min * Estimated creatinine clearance for patients >= 18 years old will be estimated by the Jelliffe equation modified for body surface area (BSA); patients with creatinine clearance estimated > 70ml/min by this formula are eligible; if the creatinine clearance estimated by the Jelliffe method is >= 50 mL/min but =< 70 mL/min, then a second method to confirm a creatinine clearance of >= 50 mL/min is required; methods of estimating glomerular filtration rate (GFR) that can be used for this confirmation consist of a 12 or 24-hour urine creatinine clearance or a nuclear creatinine clearance test; if the confirmatory creatinine clearance is < 50 mL/min, then the patient is not eligible; if the confirmatory creatinine clearance is >= 50 mL/min, the patient is eligible; if the cause of the patient’s renal dysfunction is tumor obstructing the ureters, then eligibility can be determined by the study chair even if it does not meet these minimal requirements; for patients < 18 years old, it is strongly suggested that a radioisotope estimation of GFR be obtained; if a radioisotope test is not possible, an estimated creatinine clearance using either a 12 or 24 hour urine creatinine clearance or the Schwartz formula can be used; patients will be considered eligible if the creatinine clearance is > 70 mL/min; if the creatinine clearance estimated by the Schwartz formula or urine creatinine clearance is >= 50 mL/min but =< 70 mL/min, then a second method to confirm a creatinine clearance of >= 50 mL/min is required; methods of estimating GFR that can be used for this confirmation consist of a 12- or 24-hour urine creatinine clearance if the Schwartz formula or radioisotope method was used as the primary method or a radioisotope estimation of GFR if the Schwartz formula or urine creatinine clearance method was used as the primary method; if the confirmatory creatinine clearance is < 50 mL/min, then the patient is not eligible; if the confirmatory creatinine clearance is >= 50 mL/min, the patient is eligible
• Bilirubin =< 2.0 x upper limits of normal (ULN)
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 upper limits of normal (ULN) * Unless due to hepatic metastases in which case levels =< 5 x ULN are allowed
• No concurrent malignancy other than non-melanoma skin cancer, superficial noninvasive (pTa or pT in situ [is]) transitional cell carcinoma (TCC) of the bladder, contralateral GCT, or intratubular germ cell neoplasia; patients with a prior malignancy, but at least 2 years since any evidence of disease are allowed
• Negative serology (antibody test) for the following infectious diseases: * Human immunodeficiency virus (HIV) type 1 and 2 * Human T-cell leukemia virus (HTLV) type 1 and 2 (mandatory in United States [US] but optional in Canada and Europe) * Hepatitis B surface antigen * Hepatitis C antibody
• No late relapse with completely surgically resectable disease; patients with late relapses (defined as relapse >= 2 years from the date of completion of the last chemotherapy regimen) whose disease is completely surgically resectable are not eligible; patients with late relapses who have unresectable disease are eligible
• No large (>= 2 cm) hemorrhagic or symptomatic brain metastases until local treatment has been administered (radiation therapy or surgery); treatment may begin >= 7 days after completion of local treatment; patients with small (< 2 cm) and asymptomatic brain metastases are allowed and may be treated with radiation therapy and/or surgery concurrently with Arm A or cycles 1 and 2 of Arm B if deemed medically indicated; radiation therapy should not be given concurrently with high-dose carboplatin or etoposide
• No secondary somatic malignancy arising from teratoma (e.g., teratoma with malignant transformation) when it is actively part of the disease recurrence or progression

Exclusion Criterea