Standard-Dose Combination Chemotherapy or High-Dose Combination Chemotherapy and Stem Cell Transplant in Treating Patients With Relapsed or Refractory Germ Cell Tumors
Germ Cell Tumor, Teratoma, Choriocarcinoma
About this trial
This is an interventional treatment trial for Germ Cell Tumor
Eligibility Criteria
Documentation of Disease
- Histologic Documentation: 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)
Evidence of Disease
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 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.
Prior Treatment
Must have received 3-6 cycles of cisplatin-based chemotherapy as part of first-line (initial) chemotherapy.
- Prior POMBACE, CBOP-BEP, or GAMEC are allowed.
- Note: For patients requiring immediate treatment, 1 cycle of conventional-dose salvage chemotherapy is allowed. 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 as defined in the protocol)
- 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.
- 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 17 days prior to enrollment. A minimum of three weeks after the last day of the start of the previous chemotherapy regimen before the first day of chemotherapy on study protocol.
- Must have adequate recovery from prior surgery (eg, healed scar, resumption of diet)
- Age ≥ 14 years (≥ 18 years in Germany)
- ECOG Performance Status 0 to 2
- Male gender
Required Initial Laboratory Values:
- Absolute Neutrophil Count (ANC) ≥ 1,500/mm^3
- Platelet Count ≥ 100,000/mm^3
- Calculated creatinine clearance ≥ 50 mL/min
- Bilirubin ≤ 2.0 x upper limits of normal (ULN)
- AST/ALT ≤ 2.5 x upper limits of normal (ULN)
- No concurrent malignancy other than non-melanoma skin cancer, superficial noninvasive (pTa or pTis) 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 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.
Sites / Locations
- Children's Hospital of Alabama
- UC San Diego Moores Cancer Center
- Loma Linda University Medical Center
- USC / Norris Comprehensive Cancer Center
- Kaiser Permanente-Oakland
- Stanford Cancer Institute Palo Alto
- UCSF Medical Center-Mission Bay
- Alfred I duPont Hospital for Children
- MedStar Georgetown University Hospital
- University of Florida Health Science Center - Gainesville
- Nemours Children's Clinic-Jacksonville
- Nicklaus Children's Hospital
- Miami Cancer Institute
- Arnold Palmer Hospital for Children
- Johns Hopkins All Children's Hospital
- Saint Joseph's Hospital/Children's Hospital-Tampa
- Emory University Hospital/Winship Cancer Institute
- Northwestern University
- Rush University Medical Center
- University of Illinois
- University of Chicago Comprehensive Cancer Center
- Ascension Via Christi Hospitals Wichita
- Cancer Center of Kansas - Wichita
- Ochsner Medical Center Jefferson
- Dana-Farber Cancer Institute
- University of Michigan Comprehensive Cancer Center
- Spectrum Health at Butterworth Campus
- University of Michigan Health - West
- Children's Hospitals and Clinics of Minnesota - Minneapolis
- Mayo Clinic in Rochester
- Washington University School of Medicine
- Nebraska Methodist Hospital
- Summerlin Hospital Medical Center
- Memorial Sloan Kettering Basking Ridge
- Hackensack University Medical Center
- Memorial Sloan Kettering Monmouth
- Saint Joseph's Regional Medical Center
- Roswell Park Cancer Institute
- Memorial Sloan Kettering Commack
- Memorial Sloan Kettering Westchester
- Memorial Sloan Kettering Cancer Center
- Memorial Sloan Kettering Nassau
- UNC Lineberger Comprehensive Cancer Center
- Carolinas Medical Center/Levine Cancer Institute
- Cincinnati Children's Hospital Medical Center
- Ohio State University Comprehensive Cancer Center
- University of Oklahoma Health Sciences Center
- Children's Hospital of Philadelphia
- University of Pennsylvania/Abramson Cancer Center
- University of Pittsburgh Cancer Institute (UPCI)
- Rhode Island Hospital
- Prisma Health Cancer Institute - Spartanburg
- Medical University of South Carolina
- Prisma Health Cancer Institute - Easley
- Saint Francis Hospital
- BI-LO Charities Children's Cancer Center
- Prisma Health Cancer Institute - Butternut
- Prisma Health Cancer Institute - Faris
- Prisma Health Greenville Memorial Hospital
- Saint Francis Cancer Center
- Prisma Health Cancer Institute - Eastside
- Prisma Health Cancer Institute - Greer
- Prisma Health Cancer Institute - Seneca
- Spartanburg Medical Center
- Saint Jude Children's Research Hospital
- The Children's Hospital at TriStar Centennial
- Vanderbilt University/Ingram Cancer Center
- El Paso Children's Hospital
- M D Anderson Cancer Center
- Seattle Children's Hospital
- Marshfield Medical Center-EC Cancer Center
- Marshfield Medical Center-Marshfield
- Medical College of Wisconsin
- Marshfield Clinic-Minocqua Center
- Marshfield Medical Center-Rice Lake
- Marshfield Medical Center-River Region at Stevens Point
- Marshfield Medical Center - Weston
- Royal Prince Alfred Hospital
- Princess Alexandra Hospital
- Box Hill Hospital
- Peter MacCallum Cancer Centre
- Institut Jules Bordet
- University Hospital Saint Luc
- Rigshospitalet University Hospital
- Centre Leon Berard
- Institut Paoli Calmettes
- Hopital Tenon/Assistance Publique - Hopitaux de Paris
- CHRU Strasbourg - Hospital Civil
- Center Claudius Regaud
- Centre Alexis Vautrin
- Gustave Roussy
- Technical University Dresden
- University of Berlin Charite Campus Benjamin Franklin
- University of Dusseldorf
- University of Essen
- University Medical Center Hamburg-Eppendorf
- UniversitaetsKlinikum Heidelberg
- GK-Mittelrhein Saint Martin's
- Philipps University Marburg
- Rotkreuzklinikum Munchen
- Klinikum Nurnberg Nord
- University Hospital Ulm
- Saint James Hospital
- Ospedale di Circolo di Busto Arsizio
- Istituto Scientifico Romagnolo
- Istituto Nazionale Tumori
- San Matteo Hospital
- The Netherlands Cancer Institute
- University Medical Center Groningen
- Radboud University Nijmegen Medical Centre
- Hospital De La Santa Creu I Sant Pau
- Duran i Reynals Hospital-Catalan Institute of Oncology
- Hospital Universitario 12 de Octubre
- Hospital General Universitario Morales Meseguer
- Inselspital
- Hopitaux Universitaires de Geneve
- University Hospital Zurich
- Saint Bartholomew's Hospital
- Christie Hospital
- Weston Park Hospital
- Southampton General Hospital
- Saint James's University Hospital
- Beatson Oncology Center
- Nottingham City Hospital
- The Royal Marsden NHS Foundation Trust - Sutton
Arms of the Study
Arm 1
Arm 2
Other
Other
Arm A: TIP
Arm B: TI-CE
Patients will receive treatment for 4 cycles administered every 21 days. Cycles 1-4 (1 cycle = 21 days) paclitaxel 250 mg/m^2 IV over 24 hours on Day 1 including premedication as defined in the protocol (eg, dexamethasone, diphenhydramine and H2 blocker) ifosfamide 1500 mg/m^2 IV daily on Days 2-5 with mesna protection as defined in the protocol cisplatin 25 mg/m^2 IV daily on Days 2-5 pegylated G-CSF 6 mg subcutaneous on Day 6 or 7 or G-CSF as defined in the protocol on Days 6-18 Patients may commence with each Arm A cycle provided they meet the criteria as defined in the protocol.
Patients will receive treatment for a total of 5 cycles. Cycles 1-2 (1 cycle = 14 days) paclitaxel 200 mg/m^2 IV over 3 hours on Day 1 including premedication as defined in the protocol (eg, dexamethasone, diphenhydramine and H2 blocker) ifosfamide 2000 mg/m^2 IV daily on Days 1-3 with mesna protection as defined in the protocol G-CSF 10 µg/kg subcutaneously on Days 3-15 (cycle 1) and Days 3-14 (cycle 2) or pegylated G-CSF 6 mg subcutaneous on Day 4 or 6 (cycle 1) and Day 4 or 5 (cycle 2) leukapheresis every 14 days, if there is an inadequate number of CD34+ cells/kg collected in cycle 1 Cycles 3-5 (1 cycle = 21 days) carboplatin daily on Days 1-3 etoposide 400 mg/m^2 daily on Days 1-3 stem cell reinfusion on day 5 pegylated G-CSF 6 mg subcutaneously or G-CSF at approximately 5 µg/kg daily on Days 5-15 Patients may commence with each Arm B cycle provided they meet the criteria as defined in the protocol.