Clinical trial · Interventional

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

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

NCT00047320CI-TRIAL-00031672completedPhase 2Results postedClinicalTrials.gov clinicaltrialsPublishedExplore in graph →

Summary

Brief summary (as posted)

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.

Conditions

Conditions (3)

Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.

Condition (as posted)	Mapped entity	Match	Confidence
Brain Tumor	Brain Neoplasm	ALIAS	0.90
Central Nervous System Tumors	Central Nervous System Neoplasm	ALIAS	0.90
Childhood Germ Cell Tumor	Childhood Germ Cell Tumor	ONTOLOGY_EXACT	0.98

Interventions

Interventions (9)

Intervention	Type	Mapped drug	Match
adjuvant therapy	Procedure	—	UNRESOLVED
carboplatin	Drug	Carboplatin	ALIAS
conventional surgery	Procedure	—	UNRESOLVED
etoposide	Drug	Etoposide	ALIAS
ifosfamide	Drug	Ifosfamide	ALIAS
neoadjuvant therapy	Procedure	—	UNRESOLVED
peripheral blood stem cell transplantation	Procedure	—	UNRESOLVED
radiation therapy	Radiation	—	UNRESOLVED
thiotepa

Design

Arms and outcomes

Arms (1)

type
EXPERIMENTAL
label
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.
interventionNames
1. Drug: carboplatin
2. Drug: etoposide
3. Drug: ifosfamide
4. Drug: thiotepa
5. Procedure: adjuvant therapy
6. Procedure: conventional surgery
7. Procedure: neoadjuvant therapy
8. Procedure: peripheral blood stem cell transplantation
9. Radiation: radiation therapy

Primary outcomes (1)

measure
Response to Induction Chemotherapy
timeFrame
18 weeks

Eligibility

Eligibility (as posted)

Sex: All
Minimum age: 3 Years
Maximum age: 24 Years

Show eligibility criteria text

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

References

Publications (1)

DERIVEDFangusaro J, Wu S, MacDonald S, Murphy E, Shaw D, Bartels U, Khatua S, Souweidane M, Lu HM, Morris D, Panigrahy A, Onar-Thomas A, Fouladi M, Gajjar A, Dhall G. Phase II Trial of Response-Based Radiation Therapy for Patients With Localized CNS Nongerminomatous Germ Cell Tumors: A Children's Oncology Group Study. J Clin Oncol. 2019 Dec 1;37(34):3283-3290. doi: 10.1200/JCO.19.00701. Epub 2019 Sep 23. PMID 31545689

Registry

Dates and enrollment

Start: Jan 1, 2004
Primary completion: Feb 1, 2009
Completion: Feb 1, 2009
First posted: Jan 27, 2003
Last update posted: Feb 14, 2018
Results first posted: Feb 27, 2014
Enrollment: 104 (actual)
Lead sponsor: Children's Oncology Group NETWORK
Collaborators: National Cancer Institute (NCI)
Keywords: 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

Data updated 22 days agoSource updated Feb 14, 2018source: clinicaltrials

Locations

Locations by country (106)

Country	Sites

United States	90	0
Canada	9	0
Australia	3	0
Switzerland	2	0
New Zealand	2	0