Brief 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
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
Brief Summary
RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from
dividing so they stop growing or die. Giving a chemotherapy drug before surgery may shrink
the tumor so that it is no longer present by conventional imaging and tumor markers from
serum and cerebrospinal fluid. Radiation therapy uses high-energy x-rays to damage tumor
cells. Peripheral stem cell transplantation may allow the doctor to give higher doses of
chemotherapy drugs and kill more tumor cells. Combining different types of therapy may kill
more tumor cells.
PURPOSE: This Phase II trial is studying how well neoadjuvant chemotherapy with or without
surgery and with or without high dose chemotherapy and peripheral stem cell transplantation,
can increase response rates prior to radiation therapy and increase progression free and
overall surviving patients with newly diagnosed intracranial germ cell tumors.
Detailed Description
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.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Response to Induction Chemotherapy
Secondary Outcome
The Probability of Event-free Survival (EFS)
Condition
Brain Tumor
Intervention
carboplatin
Study Arms / Comparison Groups
Radiation Therapy (CR from Induction)
Description: Patients will receive 6 cycles of Induction chemotherapy consisting of carboplatin and etoposide (Cycles 1, 3, and 5) alternating with ifosfamide and etoposide (Cycles 2, 4, and 6). The entire length of Induction is 18 weeks unless delay occurs due to myelosuppression or unanticipated toxicity. Each cycle of Induction will begin when ANC > 750/L and platelets > 75,000/L and when off filgrastim (G-CSF) for at least 48 hours. Following the Induction phase (weeks 0-18) those patient in CR will undergo radiation therapy.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
104
Start Date
January 2004
Completion Date
February 2009
Primary Completion Date
February 2009
Eligibility 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 mIU/mL or any serum/CSF
alpha-fetoprotein (AFP) levels greater than 10 ng/ml or above institutional norm
- Histologically unconfirmed pineal and/or suprasellar tumors with serum/CSF beta
HCG levels greater than 50 mIU/mL or AFP levels greater than 10 ng/ml or above
institutional norm
- Patients with normal AFP and beta HCG < 50 mIU/mL 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
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/mm^3
- Platelet count at least 100,000/mm^3 (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
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
Gender
All
Ages
3 Years - 24 Years
Accepts Healthy Volunteers
No
Contacts
Stewart Goldman, MD, ,
Location Countries
Australia
Location Countries
Australia
Administrative Informations
NCT ID
NCT00047320
Organization ID
ACNS0122
Secondary IDs
CDR0000257664
Responsible Party
Sponsor
Study Sponsor
Children's Oncology Group
Collaborators
National Cancer Institute (NCI)
Study Sponsor
Stewart Goldman, MD, Study Chair, Ann & Robert H Lurie Children's Hospital of Chicago
Verification Date
January 2018