Chemotherapy Plus Peripheral Stem Cell Transplantation in Treating Infants With Malignant Brain or Spinal Cord Tumors

Sarcoma Clinical Trial

Official title:

A Pilot Study of Intensive Chemotherapy With Peripheral Stem Cell Support for Infants With Malignant Brain Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00003141
• Other study ID #: 99703
• Secondary ID: COG-99703CCG-997
• Status: Completed
• Phase: Phase 1
• First received: November 1, 1999
• Last updated: March 27, 2014
• Start date: March 1998
• Est. completion date: October 2011

Study information

• Verified date: March 2014
• Source: Children's Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplantation may allow the doctors to give higher doses of chemotherapy drugs and kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of combination chemotherapy plus peripheral stem cell transplantation in treating infants with malignant brain or spinal cord tumors.

Description:

OBJECTIVES:

• Determine the maximum tolerated dose of thiotepa in infants with malignant brain or spinal cord tumors receiving intensive chemotherapy.

• Determine the feasibility and toxicity of intensive chemotherapy with peripheral blood stem cell (PBSC) rescue in these patients.

• Assess the feasibility of harvesting PBSCs in these patients.

• Determine the complete response rate and overall event-free survival rate in patients treated with this regimen.

OUTLINE: This is a pilot, multicenter study.

Patients undergo surgery for diagnosis and maximal tumor resection.

Within 6 weeks of surgery or when stable, patients begin induction chemotherapy comprising cisplatin IV over 6 hours on day 0; vincristine IV on days 0, 7, and 14; cyclophosphamide IV over 1 hour on days 1-2; and etoposide IV over 1 hour on days 0-2. Twenty four hours after the last cyclophosphamide dose, patients receive filgrastim (G-CSF) subcutaneously (SC) and undergo peripheral blood stem cell harvest 2 days later. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.

Within 6 weeks after induction chemotherapy, patients receive consolidation chemotherapy comprising carboplatin IV over 2 hours on days 0-1 followed immediately by escalating doses of thiotepa IV over 2 hours. Patients then undergo peripheral blood stem cell transplantation 48 hours after the last thiotepa dose. Patients receive G-CSF SC daily on days 3 to 21. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.

Patients experiencing dose-limiting toxicity due to thiotepa are removed from the study.

Patients are followed at 4 weeks, every 3 months for 1 year, every 6 months for 3 years, and then annually for 3 years or until relapse.

PROJECTED ACCRUAL: A total of 83 patients will be accrued for this study within 1 year.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 94
• Est. completion date: October 2011
• Est. primary completion date: December 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 2 Years

Eligibility

DISEASE CHARACTERISTICS:

• Histologically proven malignant brain or spinal cord tumor, including the following:

• Primitive neuroectodermal tumor

• Ganglioneuroblastoma

• Medulloblastoma neuroblastoma

• Desmoplastic medulloblastoma

• Medulloepithelioma

• Ependymoma neuroepithelioma

• Anaplastic ependymoma germ cell tumor

• Astrocytoma germinoma

• Anaplastic astrocytoma

• Embryonal carcinoma

• Glioblastoma endodermal sinus tumor

• Gliosarcoma malignant teratoma

• Choroid plexus carcinoma

• Mixed germ cell tumor

• Cerebellar sarcoma

• Pineoblastoma

• Atypical teratoid/rhabdoid tumor

• Choriocarcinoma

• Teratoma (malignant or with malignant transformations)

• Diffusely involved brain stem tumors allowed if there is evidence of brain stem glioma by CT scan or MRI

PATIENT CHARACTERISTICS:

Age:

• 6 months to less than 3 years

Performance Status:

• Not specified

Life Expectancy:

• More than 8 weeks

Hematopoietic:

• Absolute neutrophil count greater than 1,000/mm^3

• Platelet count greater than 100,000/mm^3

Hepatic:

• Bilirubin less than 2.0 mg/dL

Renal:

• Glomerular filtration rate or creatinine clearance greater than 70 mL/min

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior biologic therapy

Chemotherapy:

• No prior chemotherapy

Endocrine therapy:

• Prior corticosteroids allowed

Radiotherapy:

• No prior radiotherapy

Surgery:

• No more than 6 weeks since prior surgery

• Recovered from prior surgery (stable)

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain Neoplasms
• Brain Tumors
• Central Nervous System Neoplasms
• Central Nervous System Tumors
• Neoplasms
• Nervous System Neoplasms
• Neuroblastoma
• Sarcoma

Intervention

Biological:
• filgrastim
Given IV

Drug:
• carboplatin
Given IV
• cisplatin
Given IV
• cyclophosphamide
Given IV
• etoposide
Given IV
• thiotepa
Given IV
• vincristine sulfate
Given IV

Procedure:
• conventional surgery

• peripheral blood stem cell transplantation

Locations

Country	Name	City	State
Australia	Princess Margaret Hospital for Children	Perth	Western Australia
Canada	Allan Blair Cancer Centre at Pasqua Hospital	Regina	Saskatchewan
Canada	Hospital for Sick Children	Toronto	Ontario
Canada	Children's & Women's Hospital of British Columbia	Vancouver	British Columbia
Canada	CancerCare Manitoba	Winnipeg	Manitoba
United States	Akron Children's Hospital	Akron	Ohio
United States	Texas Tech University Health Sciences Center School of Medicine - Amarillo	Amarillo	Texas
United States	C.S. Mott Children's Hospital at University of Michigan Medical Center	Ann Arbor	Michigan
United States	AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus	Atlanta	Georgia
United States	MBCCOP - Medical College of Georgia Cancer Center	Augusta	Georgia
United States	Children's Hospital Center for Cancer and Blood Disorders	Aurora	Colorado
United States	Albert Einstein Cancer Center at Albert Einstein College of Medicine	Bronx	New York
United States	Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill	Chapel Hill	North Carolina
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	Rainbow Babies and Children's Hospital	Cleveland	Ohio
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Dayton Children's - Dayton	Dayton	Ohio
United States	Presbyterian - St. Luke's Medical Center	Denver	Colorado
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	CCOP - MeritCare Hospital	Fargo	North Dakota
United States	Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center	Farmington	Connecticut
United States	Cook Children's Medical Center - Fort Worth	Fort Worth	Texas
United States	Butterworth Hospital at Spectrum Health	Grand Rapids	Michigan
United States	Penn State Children's Hospital	Hershey	Pennsylvania
United States	Indiana University Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	Holden Comprehensive Cancer Center at University of Iowa	Iowa City	Iowa
United States	CCOP - Kalamazoo	Kalamazoo	Michigan
United States	Children's Mercy Hospital	Kansas City	Missouri
United States	CCOP - Nevada Cancer Research Foundation	Las Vegas	Nevada
United States	Lucille P. Markey Cancer Center at University of Kentucky	Lexington	Kentucky
United States	Childrens Hospital Los Angeles	Los Angeles	California
United States	Jonsson Comprehensive Cancer Center at UCLA	Los Angeles	California
United States	Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center	Los Angeles	California
United States	Kosair Children's Hospital	Louisville	Kentucky
United States	Covenant Children's Hospital	Lubbock	Texas
United States	Children's Hospital Central California	Madera	California
United States	Winthrop University Hospital	Mineola	New York
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	Carol G. Simon Cancer Center at Morristown Memorial Hospital	Morristown	New Jersey
United States	Overlook Hospital	Morristown	New Jersey
United States	Beth Israel Medical Center - Petrie Division	New York	New York
United States	Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center	New York	New York
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	NYU Cancer Institute at New York University Medical Center	New York	New York
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	Children's Hospital of Orange County	Orange	California
United States	St. Joseph's Hospital and Medical Center	Paterson	New Jersey
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania
United States	Knight Cancer Institute at Oregon Health and Science University	Portland	Oregon
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	Kaiser Permanente Medical Center - Oakland	Sacramento	California
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	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California
United States	Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center	Savannah	Georgia
United States	Children's Hospital and Regional Medical Center - Seattle	Seattle	Washington
United States	Group Health Central Hospital	Seattle	Washington
United States	Avera Cancer Institute	Sioux Falls	South Dakota
United States	Sanford Cancer Center at Sanford USD Medical Center	Sioux Falls	South Dakota
United States	Deaconess Medical Center	Spokane	Washington
United States	Children's Hospitals and Clinics of Minnesota - St. Paul	St. Paul	Minnesota
United States	Mary Bridge Children's Hospital and Health Center - Tacoma	Tacoma	Washington
United States	Medical University of Ohio Cancer Center	Toledo	Ohio
United States	Children's National Medical Center	Washington	District of Columbia
United States	Lombardi Comprehensive Cancer Center at Georgetown University Medical Center	Washington	District of Columbia
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, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Feasibility	Demonstrate the feasibility of administering this regimen, to select an acceptable Thiotepa dose for Consolidation therapy, and to document significant toxicities and estimate their overall rates	Up to 4 weeks after completion of study treatment	Yes
Primary	Maximal tolerated dose of thiotepa for consolidation therapy	The dose level will be assigned within 3 working days prior to beginning Consolidation.	9 weeks	Yes
Primary	Overall rates of significant toxicities including grade IV ototoxicity, electrolytic wasting (grade IV), and hemorrhagic cystitis (grade IV)	Estimates will be obtained using life-table methods with an event defined as the first occurrence of toxicity. Graded using the CCG Toxicity and Complications Criteria.	Up to 6 years	Yes
Secondary	Event Free Survival		From the time of study entry to the first occurrence of death by any cause, progression or recurrence of disease or occurrence of a second malignant neoplasm, assessed up	No