ACNS0122: A Phase II Study to Assess the Ability of Neoadjuvant Chemotherapy +/- Second Look Surgery to Eliminate All Measurable Disease Prior to Radiotherapy for Non-Germinomatous Germ Cell Tumor (NGGCT)
| Type | Status | Age Range (yrs.) | Sponsor | Protocol ID |
|---|
| Treatment | Active | 3 - 24 | COG | ACNS0122 |
Outline
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.
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.
Projected Accrual
A total of 80-100 patients will be accrued for this study within 36-42 months.
Entry Criteria
Disease Characteristics:
- One of the following diagnoses:
- Histologically confirmed intracranial non-germinomatous germ cell tumor of 1 of the following types:
- Endodermal sinus tumor (yolk sac tumor)
- Embryonal carcinoma
- Choriocarcinoma
- Immature teratoma and teratoma with malignant transformation
- Mixed germ cell tumor
- Histologically confirmed germinoma with elevation of serum/CSF beta human chorionic gonadotropin (HCG) levels greater than 50 IU/dL or any serum/CSF alpha-fetoprotein (AFP) levels greater than 10 IU/dL
- Histologically unconfirmed pineal and/or suprasellar tumors with serum/CSF beta HCG levels greater than 50 IU/dL or AFP levels greater than 10 IU/dL
- Initial diagnosis within the past 31 days
Patient Characteristics:
Age
Performance status
- No minimum performance level
Life expectancy
Hematopoietic
- Absolute neutrophil count at least 1,000/mm3
- Platelet count at least 100,000/mm3 (transfusion independent)
- Hemoglobin at least 10.0 g/dL (transfusion allowed)
Hepatic - Bilirubin no greater than 1.5 times upper limit of normal (ULN)
- ALT no greater than 2.5 times ULN
Renal
- Creatinine no greater than 1.5 times ULN OR
- Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min
Pulmonary
Other
- Seizure disorders allowed
- No patients in status or coma
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patient must use effective contraception
Prior Concurrent Therapy:
Biologic therapy
Chemotherapy
Endocrine therapy
- Prior corticosteroids allowed
- Concurrent corticosteroids allowed
- Concurrent endocrine replacement therapy allowed (e.g., L-thyroxine, testosterone, estrogen, desmopressin acetate)
- No concurrent growth hormone therapy
Radiotherapy
Surgery
- More than 1 prior surgery allowed
Other
- No other prior therapy for malignancy
