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

Brain Tumor Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00047320
• Other study ID #: ACNS0122
• Secondary ID: CDR0000257664COG
• Status: Completed
• Phase: Phase 2
• First received: October 3, 2002
• Last updated: January 17, 2018
• Start date: January 2004
• Est. completion date: February 2009

Study information

• Verified date: January 2018
• Source: Children's Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 104
• Est. completion date: February 2009
• Est. primary completion date: February 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years to 24 Years

Eligibility

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

Related Conditions & MeSH terms

• Brain Tumor
• Central Nervous System Neoplasms
• Central Nervous System Tumors
• Childhood Germ Cell Tumor
• Neoplasms
• Neoplasms, Germ Cell and Embryonal
• Nervous System Neoplasms

Intervention

Drug:
• carboplatin
Given IV
• etoposide
Given IV
• ifosfamide
Given IV
• thiotepa
Given IV

Procedure:
• adjuvant therapy

• conventional surgery

• neoadjuvant therapy

• peripheral blood stem cell transplantation

Radiation:
• radiation therapy
craniospinal irradiation

Locations

Country	Name	City	State
Australia	Royal Children's Hospital	Brisbane	Queensland
Australia	Royal Children's Hospital	Parkville	Victoria
Australia	Princess Margaret Hospital for Children	Perth	Western Australia
Canada	IWK Health Centre	Halifax	Nova Scotia
Canada	McMaster Children's Hospital at Hamilton Health Sciences	Hamilton	Ontario
Canada	Hopital Sainte Justine	Montreal	Quebec
Canada	Montreal Children's Hospital at McGill University Health Center	Montreal	Quebec
Canada	Centre Hospitalier Universitaire de Quebec	Quebec
Canada	Saskatoon Cancer Centre at the University of Saskatchewan	Saskatoon	Saskatchewan
Canada	Janeway Children's Health and Rehabilitation Centre	St. John's	Newfoundland and Labrador
Canada	Hospital for Sick Children	Toronto	Ontario
Canada	Children's & Women's Hospital of British Columbia	Vancouver	British Columbia
New Zealand	Starship Children's Health	Auckland
New Zealand	Christchurch Hospital	Christchurch
Switzerland	Swiss Pediatric Oncology Group Bern	Bern
Switzerland	Swiss Pediatric Oncology Group Geneva	Geneva
United States	Akron Children's Hospital	Akron	Ohio
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Winship Cancer Institute of Emory University	Atlanta	Georgia
United States	MBCCOP - Medical College of Georgia Cancer Center	Augusta	Georgia
United States	Dell Children's Medical Center of Central Texas	Austin	Texas
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham	Birmingham	Alabama
United States	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute	Boston	Massachusetts
United States	Floating Hospital for Children at Tufts - New England Medical Center	Boston	Massachusetts
United States	Albert Einstein Cancer Center at Albert Einstein College of Medicine	Bronx	New York
United States	Hollings Cancer Center at Medical University of South Carolina	Charleston	South Carolina
United States	West Virginia University Health Sciences Center - Charleston	Charleston	West Virginia
United States	Blumenthal Cancer Center at Carolinas Medical Center	Charlotte	North Carolina
United States	Ann & Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	University of Chicago Cancer Research Center	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Driscoll Children's Hospital	Corpus Christi	Texas
United States	Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas	Dallas	Texas
United States	Children's Medical Center - Dayton	Dayton	Ohio
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	Southern California Permanente Medical Group	Downey	California
United States	Duke Comprehensive Cancer Center	Durham	North Carolina
United States	Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center	Farmington	Connecticut
United States	Lee Cancer Care of Lee Memorial Health System	Fort Myers	Florida
United States	Cook Children's Medical Center - Fort Worth	Fort Worth	Texas
United States	University of Florida Shands Cancer Center	Gainesville	Florida
United States	Butterworth Hospital at Spectrum Health	Grand Rapids	Michigan
United States	St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin
United States	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan
United States	Hackensack University Medical Center Cancer Center	Hackensack	New Jersey
United States	Penn State Cancer Institute at Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Indiana University Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	St. Vincent Indianapolis Hospital	Indianapolis	Indiana
United States	University of Mississippi Cancer Clinic	Jackson	Mississippi
United States	Nemours Children's Clinic	Jacksonville	Florida
United States	Children's Mercy Hospital	Kansas City	Missouri
United States	Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center	Kansas City	Kansas
United States	Breslin Cancer Center at Ingham Regional Medical Center	Lansing	Michigan
United States	Arkansas Cancer Research Center at University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Loma Linda University Cancer Institute at Loma Linda University Medical Center	Loma Linda	California
United States	Jonathan Jaques Children's Cancer Center at Miller Children's Hospital	Long Beach	California
United States	Childrens Hospital Los Angeles	Los Angeles	California
United States	Covenant Children's Hospital	Lubbock	Texas
United States	Children's Hospital Central California	Madera	California
United States	Marshfield Clinic - Marshfield Center	Marshfield	Wisconsin
United States	St. Jude Children's Research Hospital	Memphis	Tennessee
United States	Miami Children's Hospital	Miami	Florida
United States	University of Miami Sylvester Comprehensive Cancer Center - Miami	Miami	Florida
United States	Midwest Children's Cancer Center	Milwaukee	Wisconsin
United States	Children's Hospitals and Clinics of Minnesota - Minneapolis	Minneapolis	Minnesota
United States	Masonic Cancer Center at University of Minnesota	Minneapolis	Minnesota
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee
United States	Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School	New Brunswick	New Jersey
United States	Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center	New York	New York
United States	NYU Cancer Institute at New York University Medical Center	New York	New York
United States	Newark Beth Israel Medical Center	Newark	New Jersey
United States	Children's Hospital of The King's Daughters	Norfolk	Virginia
United States	Children's Hospital and Research Center Oakland	Oakland	California
United States	Oklahoma University Cancer Institute	Oklahoma City	Oklahoma
United States	Children's Hospital of Orange County	Orange	California
United States	Florida Hospital Cancer Institute at Florida Hospital Orlando	Orlando	Florida
United States	Advocate Lutheran General Cancer Care Center	Park Ridge	Illinois
United States	St. Joseph's Hospital and Medical Center	Paterson	New Jersey
United States	Sacred Heart Cancer Center at Sacred Heart Hospital	Pensacola	Florida
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	St. Christopher's Hospital for Children	Philadelphia	Pennsylvania
United States	Phoenix Children's Hospital	Phoenix	Arizona
United States	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	Oregon Health and Science University Cancer Institute	Portland	Oregon
United States	Rhode Island Hospital Comprehensive Cancer Center	Providence	Rhode Island
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	Sutter Cancer Center	Sacramento	California
United States	Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis	Saint Louis	Missouri
United States	All Children's Hospital	Saint Petersburg	Florida
United States	Primary Children's Medical Center	Salt Lake City	Utah
United States	Methodist Children's Hospital of South Texas	San Antonio	Texas
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	Rady Children's Hospital - San Diego	San Diego	California
United States	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California
United States	Sanford Cancer Center at Sanford USD Medical Center	Sioux Falls	South Dakota
United States	Simmons Cooper Cancer Institute	Springfield	Illinois
United States	Stanford Cancer Center	Stanford	California
United States	SUNY Upstate Medical University Hospital	Syracuse	New York
United States	St. Joseph's Cancer Institute at St. Joseph's Hospital	Tampa	Florida
United States	New York Medical College	Valhalla	New York
United States	Children's National Medical Center	Washington	District of Columbia
United States	Kaplan Cancer Center at St. Mary's Medical Center	West Palm Beach	Florida
United States	Alfred I. duPont Hospital for Children	Wilmington	Delaware

Sponsors (2)

Lead Sponsor	Collaborator
Children's Oncology Group	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Australia,  Canada,  New Zealand,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response to Induction Chemotherapy	A patient who achieves a complete or partial response, defined a reduction of at least 65% in tumor size after induction chemotherapy will be considered to have experienced response.	18 weeks
Secondary	The Probability of Event-free Survival (EFS)	Event-free Survival was defined as time from study entry to death from any cause, disease progression or recurrence, or second malignant neoplasm. Event-free survival was estimated by KM estimate.	At 3 years from study entry
Secondary	Progression-free Survival (PFS)	Progression-free Survival was defined as time from study entry to disease progression or recurrence. Deaths that are clearly unrelated to disease progression, and second neoplasms are censored in this analysis. Progression -free survival was estimated by KM estimate.	At 3 years from study entry
Secondary	Overall Survival (OS)	Overall Survival was defined as time from study entry to death from any cause. Overall survival was estimated by KM estimate.	At 3 years from study entry
Secondary	Number of Patients Experiencing Toxic Death	Toxic death, defined as death predominantly attributable to treatment-related causes.	During chemotherapy (up to 18 weeks)
Secondary	Occurrence of Non-hematological Grade 4 Toxicity Occurrence of Nonhematological Grade 4 Toxicity	The number of patients who experienced non-hematological grade 4 toxicities anytime during chemotherapy.	During chemotherapy(up to 18 weeks)