Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Neoadjuvant Chemotherapy With or Without Second-Look Surgery Followed by Radiation Therapy With or Without Peripheral Stem Cell Transplantation in Treating Patients With Intracranial Germ Cell Tumors

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Closed	3 to 24 at diagnosis	NCI	COG-ACNS0122 NCT00047320, ACNS0122

Objectives

1. Determine the response rate of patients with non-germinomatous germ cell tumors treated with neoadjuvant chemotherapy.
2. 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).
3. 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.
4. Determine patterns of recurrence in patients treated with this regimen.
5. 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.

Entry Criteria

Disease Characteristics:

• One of the following diagnoses:
  • Histologically confirmed intracranial non-germinomatous germ cell tumor (NGGCT) 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 or institutional norm
  • 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 or institutional norm



• Patients with normal AFP and beta HCG < 50 IU/dL without histologic diagnosis of a NGGCT or patients with pure germinoma without elevation of tumor marker are ineligible



• Initial diagnosis within the past 31 days

Prior/Concurrent Therapy:

Biologic therapy

• Not specified

Chemotherapy

• Not specified

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

• Not specified

Surgery

• More than 1 prior surgery allowed

Other

• No other prior therapy for malignancy

Patient Characteristics:

Age

• 3 to 24 at diagnosis

Performance status

• No minimum performance level

Life expectancy

• At least 8 weeks

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

• No assisted ventilation

Other

• Seizure disorders allowed
• No patients in status or coma
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patient must use effective contraception

Expected Enrollment

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

Outcomes

Response (complete and partial response)
Toxic death
Occurrence of nonhematological grade 4 toxicity during chemotherapy

Event-free survival
Progression-free survival
Overall survival

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.

Trial Contact Information

Trial Lead Organizations

Children's Oncology Group

Stewart Goldman, MD, Protocol chair		Ph: 773-880-4562

Registry Information
Official Title		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
Trial Start Date		2004-01-26
Trial Completion Date		2009-07-18 (estimated)
Registered in ClinicalTrials.gov		NCT00047320
Date Submitted to PDQ		2002-08-30
Information Last Verified		2008-10-15
NCI Grant/Contract Number		CA30969, CA13539

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