Trial Information

A Phase II Study To Assess The Ability Of Neoadjuvant Chemotherapy Plus/Minus Second Look Surgery To Eliminate All Measurable Disease Prior To Radiotherapy For NGGCT

OBJECTIVES:

- Determine the response rate of patients with non-germinomatous germ cell tumors treated
with neoadjuvant chemotherapy.

- Determine the progression-free survival and overall survival of patients treated with
neoadjuvant chemotherapy with or without second-look surgery followed by radiotherapy
with or without autologous peripheral blood stem cell transplantation (PBSCT).

- Determine whether additional complete responses can be achieved after high-dose
thiotepa and etoposide with PBSCT in patients with persistently positive markers,
histological evidence of residual malignant elements, or unresectable residual tumors
after initial neoadjuvant chemotherapy.

- Determine patterns of recurrence in patients treated with this regimen.

- Correlate tumor marker response with radiographic and clinical measures of response, as
well as findings at second-look surgery in patients with radiological evidence of
residual disease.

OUTLINE:

- Induction chemotherapy:

- Courses 1, 3, and 5: Patients receive carboplatin IV over 1 hour on day 1 and
etoposide IV over 1 hour on days 1-3. Beginning on day 4, patients receive
filgrastim (G-CSF) IV or subcutaneously (SC) for 10 days or until blood counts
recover. Courses are 3 weeks in duration.

- Courses 2, 4, and 6: Patients receive etoposide IV over 1 hour followed by
ifosfamide IV over 1 hour on days 1-5. Beginning on day 6, patients receive G-CSF
IV or SC for 10 days or until blood counts recover. Courses are 3 weeks in
duration.

Patients undergo re-evaluation. Patients with a complete response (CR) go directly to
radiotherapy. Approximately 3 weeks after completion of induction chemotherapy, all patients
with less than a CR are encouraged to undergo second-look surgery.

After second-look surgery, patients with a CR or a partial response (PR) go directly to
radiotherapy. Patients with less than a PR undergo consolidation chemotherapy with
peripheral blood stem cell rescue (PBSC) followed by radiotherapy.

- Consolidation chemotherapy: Patients undergo PBSC collection. Patients receive G-CSF SC
until PBSC collection is complete. Patients then receive thiotepa IV over 3 hours
followed by etoposide IV over 3 hours on days -5 to -3. PBSCs are reinfused on day 0.
Beginning on day 1 and continuing until blood counts recover, patients receive G-CSF SC
daily.

- Radiotherapy: All patients receive radiotherapy once daily 5 days a week for 5-6 weeks
beginning after recovery from induction chemotherapy or second-look surgery or within 9
weeks after PBSC reinfusion.

Patients are followed every 3 months for 1 year, every 4 months for 1 year, every 6 months
for 1 year, and then annually thereafter.

PROJECTED ACCRUAL: A total of 80-100 patients will be accrued for this study within 36-42
months.