Protocol Summary

Protocol No.: OCR14932

Sponsor Protocol No.: A031102

Study Title
A Randomized Phase III Trial Comparing Conventional-Dose Chemotherapy Using Paclitaxel, Ifosfamide, and Cisplatin (TIP) With High-Dose Chemotherapy Using Mobilizing Paclitaxel Plus Ifosfamide Followed by High-Dose Carboplatin and Etoposide (TI-CE) as First Salvage Treatment in Relapsed or Refractory Germ Cell Tumors

Principal Investigator(s)
Slayton, William

Objective
This randomized phase III trial studies how well standard-dose combination chemotherapy works compared to high-dose combination chemotherapy and stem cell transplant in treating patients with germ cell tumors that have returned after a period of improvement or did not respond to treatment. Drugs used in chemotherapy, such as paclitaxel, ifosfamide, cisplatin, carboplatin, and etoposide, 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 chemotherapy before a stem cell transplant stops the growth of cancer cells by stopping them from dividing or killing them. Giving colony-stimulating factors, such as filgrastim or pegfilgrastim, and certain chemotherapy drugs, helps stem cells move from the bone marrow to the blood so they can be collected and stored. Chemotherapy is then given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy. It is not yet known whether high-dose combination chemotherapy and stem cell transplant are more effective than standard-dose combination chemotherapy in treating patients with refractory or relapsed germ cell tumors.

Phase: Phase III (Cancer Control)

Age Group: Both

Scope: National

Treatment
Arm A: TIP
Patients will receive treatment for 4 cycles administered every 21 days.
Paclitaxel 250 mg/m^2 IV over 24 hours on Day 1
Ifosfamide 1500 mg/m^2 IV daily on Days 2-5
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 on Days 6-18

Arm B: TI-CE
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
Ifosfamide 2000 mg/m^2 IV daily on Days 1-3
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

Detailed Eligibility
INCLUSION CRITERIA:
1. Ages 14 years old and older
2. Histologic Documentation: Confirmation of GCT histology (both seminoma and nonseminoma) on pathologic review at the center of enrollment.
3. 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.
4. 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)
5. 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.
6. 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.
7. 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.
8. No prior treatment with high-dose chemotherapy (defined as treatment utilizing stem cell rescue)
9. 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.
10. No concurrent treatment with other cytotoxic drugs or targeted therapies.
11. 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.
12. 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.
13. Must have adequate recovery from prior surgery (eg, healed scar, resumption of diet)
14. ECOG Performance Status 0 to 2
15. Male gender
16. Required Initial Laboratory Values:
17. Absolute Neutrophil Count (ANC) ≥ 1,500/mm^3
18. Platelet Count ≥ 100,000/mm^3

** Contact study team for full eligibility details.

Applicable Disease Sites
Pediatric (Childhood) Cancer

Participating Institutions
UF Gainesville : Ashley Bayne

Contact
Ashley Bayne, RN
Phone: +1 352-294-8745

Email: abayne@ufl.edu