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

NCT ID: NCT00047320

Last Updated: 2018-02-14

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

104 participants

Study Classification

INTERVENTIONAL

Study Start Date

2004-01-31

Study Completion Date

2009-02-28

Brief Summary

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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

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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.

Conditions

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Brain Tumor Central Nervous System Tumors Childhood Germ Cell Tumor

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Radiation Therapy (CR from Induction)

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.

Group Type EXPERIMENTAL

carboplatin

Intervention Type DRUG

Given IV

etoposide

Intervention Type DRUG

Given IV

ifosfamide

Intervention Type DRUG

Given IV

thiotepa

Intervention Type DRUG

Given IV

adjuvant therapy

Intervention Type PROCEDURE

conventional surgery

Intervention Type PROCEDURE

neoadjuvant therapy

Intervention Type PROCEDURE

peripheral blood stem cell transplantation

Intervention Type PROCEDURE

radiation therapy

Intervention Type RADIATION

craniospinal irradiation

Interventions

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carboplatin

Given IV

Intervention Type DRUG

etoposide

Given IV

Intervention Type DRUG

ifosfamide

Given IV

Intervention Type DRUG

thiotepa

Given IV

Intervention Type DRUG

adjuvant therapy

Intervention Type PROCEDURE

conventional surgery

Intervention Type PROCEDURE

neoadjuvant therapy

Intervention Type PROCEDURE

peripheral blood stem cell transplantation

Intervention Type PROCEDURE

radiation therapy

craniospinal irradiation

Intervention Type RADIATION

Other Intervention Names

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Paraplatin NSC #241240 VP-16 VePesid Etopophos NSC #141540 Isophosphamide Iphosphamide Z4942 Ifex NSC #109724 Tespa Thiophosphamide Triethylenethiophosphoramide Tspa WR-45312 NSC #6396 Craniospinal irradiation (CSI) followed by boost radiation to the sites of gross disease at diagnosis.

Eligibility Criteria

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Inclusion Criteria

* 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
Minimum Eligible Age

3 Years

Maximum Eligible Age

24 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Children's Oncology Group

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Stewart Goldman, MD

Role: STUDY_CHAIR

Ann & Robert H Lurie Children's Hospital of Chicago

Locations

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Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham

Birmingham, Alabama, United States

Site Status

Phoenix Children's Hospital

Phoenix, Arizona, United States

Site Status

Arkansas Cancer Research Center at University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Site Status

Southern California Permanente Medical Group

Downey, California, United States

Site Status

Loma Linda University Cancer Institute at Loma Linda University Medical Center

Loma Linda, California, United States

Site Status

Jonathan Jaques Children's Cancer Center at Miller Children's Hospital

Long Beach, California, United States

Site Status

Childrens Hospital Los Angeles

Los Angeles, California, United States

Site Status

Children's Hospital Central California

Madera, California, United States

Site Status

Children's Hospital and Research Center Oakland

Oakland, California, United States

Site Status

Children's Hospital of Orange County

Orange, California, United States

Site Status

Sutter Cancer Center

Sacramento, California, United States

Site Status

Rady Children's Hospital - San Diego

San Diego, California, United States

Site Status

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, United States

Site Status

Stanford Cancer Center

Stanford, California, United States

Site Status

Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center

Farmington, Connecticut, United States

Site Status

Alfred I. duPont Hospital for Children

Wilmington, Delaware, United States

Site Status

Children's National Medical Center

Washington D.C., District of Columbia, United States

Site Status

Lee Cancer Care of Lee Memorial Health System

Fort Myers, Florida, United States

Site Status

University of Florida Shands Cancer Center

Gainesville, Florida, United States

Site Status

Nemours Children's Clinic

Jacksonville, Florida, United States

Site Status

University of Miami Sylvester Comprehensive Cancer Center - Miami

Miami, Florida, United States

Site Status

Miami Children's Hospital

Miami, Florida, United States

Site Status

Florida Hospital Cancer Institute at Florida Hospital Orlando

Orlando, Florida, United States

Site Status

Sacred Heart Cancer Center at Sacred Heart Hospital

Pensacola, Florida, United States

Site Status

All Children's Hospital

St. Petersburg, Florida, United States

Site Status

St. Joseph's Cancer Institute at St. Joseph's Hospital

Tampa, Florida, United States

Site Status

Kaplan Cancer Center at St. Mary's Medical Center

West Palm Beach, Florida, United States

Site Status

Winship Cancer Institute of Emory University

Atlanta, Georgia, United States

Site Status

MBCCOP - Medical College of Georgia Cancer Center

Augusta, Georgia, United States

Site Status

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, United States

Site Status

University of Chicago Cancer Research Center

Chicago, Illinois, United States

Site Status

Advocate Lutheran General Cancer Care Center

Park Ridge, Illinois, United States

Site Status

Simmons Cooper Cancer Institute

Springfield, Illinois, United States

Site Status

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, United States

Site Status

St. Vincent Indianapolis Hospital

Indianapolis, Indiana, United States

Site Status

Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center

Kansas City, Kansas, United States

Site Status

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Site Status

Floating Hospital for Children at Tufts - New England Medical Center

Boston, Massachusetts, United States

Site Status

Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status

Butterworth Hospital at Spectrum Health

Grand Rapids, Michigan, United States

Site Status

Van Elslander Cancer Center at St. John Hospital and Medical Center

Grosse Pointe Woods, Michigan, United States

Site Status

Breslin Cancer Center at Ingham Regional Medical Center

Lansing, Michigan, United States

Site Status

Children's Hospitals and Clinics of Minnesota - Minneapolis

Minneapolis, Minnesota, United States

Site Status

Masonic Cancer Center at University of Minnesota

Minneapolis, Minnesota, United States

Site Status

Mayo Clinic Cancer Center

Rochester, Minnesota, United States

Site Status

University of Mississippi Cancer Clinic

Jackson, Mississippi, United States

Site Status

Children's Mercy Hospital

Kansas City, Missouri, United States

Site Status

Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis

St Louis, Missouri, United States

Site Status

Hackensack University Medical Center Cancer Center

Hackensack, New Jersey, United States

Site Status

Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School

New Brunswick, New Jersey, United States

Site Status

Newark Beth Israel Medical Center

Newark, New Jersey, United States

Site Status

St. Joseph's Hospital and Medical Center

Paterson, New Jersey, United States

Site Status

University of New Mexico Cancer Center

Albuquerque, New Mexico, United States

Site Status

NYU Cancer Institute at New York University Medical Center

New York, New York, United States

Site Status

Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center

New York, New York, United States

Site Status

SUNY Upstate Medical University Hospital

Syracuse, New York, United States

Site Status

Albert Einstein Cancer Center at Albert Einstein College of Medicine

The Bronx, New York, United States

Site Status

New York Medical College

Valhalla, New York, United States

Site Status

Blumenthal Cancer Center at Carolinas Medical Center

Charlotte, North Carolina, United States

Site Status

Duke Comprehensive Cancer Center

Durham, North Carolina, United States

Site Status

Akron Children's Hospital

Akron, Ohio, United States

Site Status

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Site Status

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, United States

Site Status

Nationwide Children's Hospital

Columbus, Ohio, United States

Site Status

Children's Medical Center - Dayton

Dayton, Ohio, United States

Site Status

Oklahoma University Cancer Institute

Oklahoma City, Oklahoma, United States

Site Status

Oregon Health and Science University Cancer Institute

Portland, Oregon, United States

Site Status

Penn State Cancer Institute at Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

Site Status

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

St. Christopher's Hospital for Children

Philadelphia, Pennsylvania, United States

Site Status

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status

Rhode Island Hospital Comprehensive Cancer Center

Providence, Rhode Island, United States

Site Status

Hollings Cancer Center at Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

Sanford Cancer Center at Sanford USD Medical Center

Sioux Falls, South Dakota, United States

Site Status

St. Jude Children's Research Hospital

Memphis, Tennessee, United States

Site Status

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

Site Status

Dell Children's Medical Center of Central Texas

Austin, Texas, United States

Site Status

Driscoll Children's Hospital

Corpus Christi, Texas, United States

Site Status

Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas

Dallas, Texas, United States

Site Status

Cook Children's Medical Center - Fort Worth

Fort Worth, Texas, United States

Site Status

Covenant Children's Hospital

Lubbock, Texas, United States

Site Status

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

Site Status

Methodist Children's Hospital of South Texas

San Antonio, Texas, United States

Site Status

Primary Children's Medical Center

Salt Lake City, Utah, United States

Site Status

Children's Hospital of The King's Daughters

Norfolk, Virginia, United States

Site Status

West Virginia University Health Sciences Center - Charleston

Charleston, West Virginia, United States

Site Status

St. Vincent Hospital Regional Cancer Center

Green Bay, Wisconsin, United States

Site Status

Marshfield Clinic - Marshfield Center

Marshfield, Wisconsin, United States

Site Status

Midwest Children's Cancer Center

Milwaukee, Wisconsin, United States

Site Status

Royal Children's Hospital

Brisbane, Queensland, Australia

Site Status

Royal Children's Hospital

Parkville, Victoria, Australia

Site Status

Princess Margaret Hospital for Children

Perth, Western Australia, Australia

Site Status

Children's & Women's Hospital of British Columbia

Vancouver, British Columbia, Canada

Site Status

Janeway Children's Health and Rehabilitation Centre

St. John's, Newfoundland and Labrador, Canada

Site Status

IWK Health Centre

Halifax, Nova Scotia, Canada

Site Status

McMaster Children's Hospital at Hamilton Health Sciences

Hamilton, Ontario, Canada

Site Status

Hospital for Sick Children

Toronto, Ontario, Canada

Site Status

Montreal Children's Hospital at McGill University Health Center

Montreal, Quebec, Canada

Site Status

Hopital Sainte Justine

Montreal, Quebec, Canada

Site Status

Saskatoon Cancer Centre at the University of Saskatchewan

Saskatoon, Saskatchewan, Canada

Site Status

Centre Hospitalier Universitaire de Quebec

Québec, , Canada

Site Status

Starship Children's Health

Auckland, , New Zealand

Site Status

Christchurch Hospital

Christchurch, , New Zealand

Site Status

Swiss Pediatric Oncology Group Bern

Bern, , Switzerland

Site Status

Swiss Pediatric Oncology Group Geneva

Geneva, , Switzerland

Site Status

Countries

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United States Australia Canada New Zealand Switzerland

References

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Fangusaro 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.

Reference Type DERIVED
PMID: 31545689 (View on PubMed)

Other Identifiers

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CDR0000257664

Identifier Type: OTHER

Identifier Source: secondary_id

COG-ACNS0122

Identifier Type: OTHER

Identifier Source: secondary_id

ACNS0122

Identifier Type: -

Identifier Source: org_study_id

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