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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
Health authority
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

Study Design


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)
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