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 - Full Text View

Sponsor:	Children's Oncology Group
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00047320

Purpose

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 can be removed. 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 followed by radiation therapy with or without peripheral stem cell transplantation work in treating patients with intracranial germ cell tumors.

Condition	Intervention	Phase
Brain and Central Nervous System Tumors Childhood Germ Cell Tumor	Biological: filgrastim Biological: graft-versus-tumor induction therapy Drug: carboplatin Drug: etoposide Drug: ifosfamide Drug: thiotepa Procedure: adjuvant therapy Procedure: conventional surgery Procedure: neoadjuvant therapy Procedure: peripheral blood stem cell transplantation Radiation: radiation therapy	Phase II

Study Type:	Interventional
Study Design:	Treatment, Open Label
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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Surgery

Drug Information available for: Thiotepa Etoposide Carboplatin Etoposide phosphate Filgrastim Ifosfamide

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Response (complete and partial response) [ Designated as safety issue: No ]
Toxic death [ Designated as safety issue: Yes ]
Occurrence of nonhematological grade 4 toxicity during chemotherapy [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Event-free survival [ Designated as safety issue: No ]
Progression-free survival [ Designated as safety issue: No ]
Overall survival [ Designated as safety issue: No ]

Estimated Enrollment:	100
Study Start Date:	January 2004
Estimated Primary Completion Date:	July 2009 (Final data collection date for primary outcome measure)

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.

Eligibility

Ages Eligible for Study:	3 Years to 24 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00047320

Show 106 Study Locations

Sponsors and Collaborators

Children's Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:

Stewart Goldman, MD

Children's Memorial Hospital

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Children's Oncology Group - Group Chair Office ( Gregory H. Reaman )
Study ID Numbers:	CDR0000257664, COG-ACNS0122
Study First Received:	October 3, 2002
Last Updated:	April 14, 2009
ClinicalTrials.gov Identifier:	NCT00047320 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

childhood central nervous system germ cell tumor
childhood teratoma
recurrent childhood malignant germ cell tumor
childhood central nervous system choriocarcinoma
childhood central nervous system embryonal tumor

childhood central nervous system germinoma
childhood central nervous system mixed germ cell tumor
childhood central nervous system teratoma
childhood central nervous system yolk sac tumor
recurrent childhood central nervous system embryonal tumor

Additional relevant MeSH terms:

Neoplasms by Histologic Type
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Nervous System Diseases
Central Nervous System Neoplasms
Carboplatin
Immunosuppressive Agents
Pharmacologic Actions
Thiotepa

Neoplasms
Ifosfamide
Neoplasms by Site
Therapeutic Uses
Neoplasms, Germ Cell and Embryonal
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Alkylating Agents
Etoposide
Antineoplastic Agents, Phytogenic
Nervous System Neoplasms

ClinicalTrials.gov processed this record on February 08, 2010