Chemotherapy Combined With Radiation Therapy for Newly Diagnosed CNS AT/RT

This study has been completed.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Mark W. Kieran, MD, PhD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT00084838
First received: June 10, 2004
Last updated: December 18, 2015
Last verified: December 2015
  Purpose

RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Giving more than one chemotherapy drug with radiation therapy may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving intrathecal and systemic combination chemotherapy together with radiation therapy works in treating young patients with newly diagnosed central nervous system (CNS) atypical teratoid/rhabdoid tumors.


Condition Intervention Phase
Central Nervous System Tumor, Pediatric
Biological: filgrastim
Drug: cisplatin
Drug: cyclophosphamide
Drug: cytarabine
Drug: dexrazoxane hydrochloride
Drug: doxorubicin hydrochloride
Drug: etoposide
Drug: leucovorin calcium
Drug: methotrexate
Drug: temozolomide
Drug: therapeutic hydrocortisone
Drug: vincristine sulfate
Radiation: radiation therapy
Drug: Dactinomycin
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Intrathecal and Systemic Chemotherapy With Radiation Therapy for Children With Central Nervous System Atypical Teratoid/Rhabdoid Tumor (AT/RT) Tumor

Resource links provided by NLM:


Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • 2-yr Overall Survival [ Time Frame: Patients are followed for survival up to 5 yrs post-therapy completion or death; As of this analysis, median follow-up among survivors was 31 months with the longest follow-up being 40 months. ] [ Designated as safety issue: No ]
    Overall survival is defined as the time from date of diagnosis to death or date of last follow-up. 2-year overall survival is the probability of patients remaining alive at 2-years from study entry estimated using Kaplan-Meier (KM) methods which censors patients at date of last follow-up. Precision of this conditional probability estimate was measured in terms of standard error. Median OS, the original primary endpoint, was not estimable based on the Kaplan-Meier method because of insufficient follow-up.


Secondary Outcome Measures:
  • Pre-Radiation Therapy Chemotherapeutic Response [ Time Frame: Assessed at study entry and pre-RT/post-CT at week 7. ] [ Designated as safety issue: No ]

    Response pre-RT/post-CT was defined as follows with overall response defined as achieving PR or CR.

    Complete Response (CR): Complete resolution of all initially demonstrable tumor on MRI or CT evaluation w/o appearance of any new areas of disease; negative CSF cytology. Partial Response (PR): >/= 50% decrease in the sum of the products of the maximum perpendicular diameters of the tumor (sum LD) relative to baseline w/o appearance of any new areas of disease; CSF cytology unchanged from that at diagnosis or clearing after being initially positive Stable Disease (SD): <50% decrease in the sum LD w/o appearance of any new areas of disease; CSF cytology unchanged from that at diagnosis or clearing after being initially positive Progressive Disease (PD): >/= 25% increase in the sum LD relative to baseline, or the appearance of any new areas of disease or appearance of positive cytology after two consecutive negative samples.



Other Outcome Measures:
  • Grade 3/4 Events [ Time Frame: Assessed during therapy up to 30 days post-therapy completion which is approximately 55 weeks for patients who completed therapy. ] [ Designated as safety issue: Yes ]
    All Grade 3-4 events based on CTCAEv2 as reported on case report forms.

  • Grade 3-4 Auditory/Hearing Events [ Time Frame: Assessed during therapy up to 30 days post-therapy completion which is approximately 55 weeks for patients who completed therapy. ] [ Designated as safety issue: Yes ]
    All Grade 3-4 Auditory/Hearing events based on CTCAEv2 as reported on case report forms.

  • Grade 3-4 Blood/Bone Marrow Events [ Time Frame: Assessed during therapy up to 30 days post-therapy completion which is approximately 55 weeks for patients who completed therapy. ] [ Designated as safety issue: Yes ]

    All Grade 3-4 Blood/Bone Marrow events based on CTCAEv2 as reported on case report forms.

    Arm Name


  • Grade 3-4 Gastrointestinal Events [ Time Frame: Assessed during therapy up to 30 days post-therapy completion which is approximately 55 weeks for patients who completed therapy. ] [ Designated as safety issue: Yes ]
    All Grade 3-4 Gastrointestinal events based on CTCAEv2 as reported on case report forms.

  • Grade 3-4 Metabolic/Laboratory Events [ Time Frame: Assessed during therapy up to 30 days post-therapy completion which is approximately 55 weeks for patients who completed therapy. ] [ Designated as safety issue: Yes ]
    All Grade 3-4 Metabolic/Laboratory events based on CTCAEv2 as reported on case report forms.

  • Grade 3-4 Infection/Febrile Neutropenia Events [ Time Frame: Assessed during therapy up to 30 days post-therapy completion which is approximately 55 weeks for patients who completed therapy. ] [ Designated as safety issue: Yes ]
    All Grade 3-4 Infection/Febrile Neutropenia events based on CTCAEv2 as reported on case report forms.

  • Grade 3-4 Neurology Events [ Time Frame: Assessed during therapy up to 30 days post-therapy completion which is approximately 55 weeks for patients who completed therapy. ] [ Designated as safety issue: Yes ]
    All Grade 3-4 Neurology events based on CTCAEv2 as reported on case report forms.

  • Grade 3-4 Pain Events [ Time Frame: Assessed during therapy up to 30 days post-therapy completion which is approximately 55 weeks for patients who completed therapy. ] [ Designated as safety issue: Yes ]
    All Grade 3-4 Pain events based on CTCAEv2 as reported on case report forms.

  • Grade 3-4 Constitutional Events [ Time Frame: Assessed during therapy up to 30 days post-therapy completion which is approximately 55 weeks for patients who completed therapy. ] [ Designated as safety issue: Yes ]
    All Grade 3-4 Constitutional events based on CTCAEv2 as reported on case report forms.

  • Grade 3-4 Muscloskeletal Events [ Time Frame: Assessed during therapy up to 30 days post-therapy completion which is approximately 55 weeks for patients who completed therapy. ] [ Designated as safety issue: Yes ]
    All Grade 3-4 Muscloskeletal events based on CTCAEv2 as reported on case report forms.

  • Grade 3-4 Hepatic Events [ Time Frame: Assessed during therapy up to 30 days post-therapy completion which is approximately 55 weeks for patients who completed therapy. ] [ Designated as safety issue: Yes ]
    All Grade 3-4 Hepatic events based on CTCAEv2 as reported on case report forms.

  • Grade 3-4 Cardiovascular Events [ Time Frame: Assessed during therapy up to 30 days post-therapy completion which is approximately 55 weeks for patients who completed therapy. ] [ Designated as safety issue: Yes ]
    All Grade 3-4 Cardiovascular events based on CTCAEv2 as reported on case report forms.

  • Grade 3-4 Pulmonary Events [ Time Frame: Assessed during therapy up to 30 days post-therapy completion which is approximately 55 weeks for patients who completed therapy. ] [ Designated as safety issue: Yes ]
    All Grade 3-4 Pulmonary events based on CTCAEv2 as reported on case report forms.

  • Grade 3-4 Renal/Genitourinary Events [ Time Frame: Assessed during therapy up to 30 days post-therapy completion which is approximately 55 weeks for patients who completed therapy. ] [ Designated as safety issue: Yes ]
    All Grade 3-4 Renal/Genitourinary events based on CTCAEv2 as reported on case report forms.

  • Grade 3-4 Dermatology Events [ Time Frame: Assessed during therapy up to 30 days post-therapy completion which is approximately 55 weeks for patients who completed therapy. ] [ Designated as safety issue: Yes ]
    All Grade 3-4 Dermatology events based on CTCAEv2 as reported on case report forms.

  • Grade 3-4 Hemorrhage Events [ Time Frame: Assessed during therapy up to 30 days post-therapy completion which is approximately 55 weeks for patients who completed therapy. ] [ Designated as safety issue: Yes ]
    All Grade 3-4 Hemorrhage events based on CTCAEv2 as reported on case report forms.

  • Grade 3-4 Allergy/Immunology [ Time Frame: Assessed during therapy up to 30 days post-therapy completion which is approximately 55 weeks for patients who completed therapy. ] [ Designated as safety issue: Yes ]
    All Grade 3-4 Allergy/Immunology events based on CTCAEv2 as reported on case report forms.


Enrollment: 25
Study Start Date: February 2003
Study Completion Date: March 2013
Primary Completion Date: February 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Multi-agent Intrathecal and Systemic CT with RT (mod IRS III)

Pre-irradiation induction therapy (wks 1-6); Chemoradiation induction therapy (wks 7-12); Post-radiation induction therapy (wks 13-18); Maintenance therapy (wks 19-44); Continuation therapy (wks 45-51)

Induction Chemotherapy: CT backbone of the IRS-III regimen [vincristine, dactinomycin, cyclophosphamide (specifically, in combination), cisplatin, doxorubicin, and imidazole carboximide (DTIC)] was modified to incl temozolomide in lieu of DTIC. Pts w/ M0 dz (and initially positive CSF cytology) rcvd intrathecal (IT) CT (alt btwn intralumbar and intraventricular routes) w/ methotrexate, cytarabine, and hydrocortisone, coinciding with a cycle of CT.

Radiation Therapy: Pts w/ M0 dz OR M+ dz aged <3y received focal RT (3D conformal or intensity-modulated delivery). Pts >3y w/ M+ dz rcvd craniospinal irradiation.

Continuation Therapy: Pts treated with either non-doxorubicin or doxorubicin dose therapy if receiving CSI or mediastinal radiotherapy or not, respectively.

Biological: filgrastim
Other Names:
  • filgrastim XM02
  • G-CSF
Drug: cisplatin
Other Names:
  • CACP
  • cis-DDP
  • cis-diamminedichloro platinum (II)
  • cis-diamminedichloroplatinum
  • Cis-dichloroammine Platinum (II)
  • Cismaplat
  • Platinol
Drug: cyclophosphamide
Other Names:
  • Ciclofosfamida
  • Ciclofosfamide
  • Claphene
  • CP monohydrate
  • CPM
  • Cyclophospham
  • Cyclophosphamid monohydrate
  • Cyclophosphamidum
  • Cyclophosphan
  • Cyclophosphanum
  • Cytophosphane
  • Mitoxan
  • Syklofosfamid
  • Zytoxan
  • Clafen
  • Cytoxan
  • Neosar
Drug: cytarabine
Other Names:
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • aracytidine
  • beta-cytosine arabinoside
  • cytarabine hydrochloride
  • cytarabinum
  • cytosine arabinoside
  • cytosine arabinosine hydrochloride
  • Cytosar-U
  • Tarabine PFS
Drug: dexrazoxane hydrochloride
Other Names:
  • Totect
  • Zinecard
Drug: doxorubicin hydrochloride
Other Names:
  • Adriamycin PFS
  • Adriamycin RDF
Drug: etoposide
Other Name: VP-16
Drug: leucovorin calcium
Other Names:
  • folinate calcium
  • folinic acid
Drug: methotrexate Drug: temozolomide
Other Name: Temodar, Methazolastone, Temodal, TMZ, CCRG-81045
Drug: therapeutic hydrocortisone Drug: vincristine sulfate
Other Names:
  • leurocristine sulfate
  • Vincasar PFS
Radiation: radiation therapy Drug: Dactinomycin
Other Names:
  • ACT-D
  • actinomycin C1
  • actinomycin D
  • actinomycin I1
  • actinomycin IV
  • actinomycin X 1
  • actinomycin-[thr-val-pro-sar-meval]
  • AD
  • dactinomycine
  • meractinomycin

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   up to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed primary intracranial Central Nervous System (CNS) atypical teratoid/rhabdoid tumor OR
  • Tumor tissue that possesses the INI-1 gene mutation
  • No metastases that disseminate outside the CNS by abdominal and chest computer tomography (CT) scans, kidney imaging, and bone marrow biopsy

    • No obstruction of cerebrospinal fluid (CSF) flow by CSF flow study
  • Definitive surgical resection of tumor within the past 35 days

PATIENT CHARACTERISTICS:

Age

  • 18 and under

Performance status

  • Karnofsky 50-100% OR
  • Lansky 50-100%

Life expectancy

  • Not specified

Hematopoietic

  • Hemoglobin > 10 g/dL
  • Absolute neutrophil count > 1,000/mm^3
  • Platelet count > 100,000/mm^3

Hepatic

  • Bilirubin ≤ 1.5 mg/dL
  • SGPT < 10 times normal

Renal

  • Creatinine ≤ 1.5 times normal

Other

  • Willing to have placement of central venous access line

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Not specified

Chemotherapy

  • No prior chemotherapy

Endocrine therapy

  • Prior steroids allowed

Radiotherapy

  • No prior radiotherapy

Surgery

  • See Disease Characteristics

Other

  • No other prior or concurrent investigational agents
  • Concurrent anticonvulsant agents allowed
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00084838

Locations
United States, California
Stanford Cancer Center
Stanford, California, United States, 94305-5826
United States, Connecticut
Yale Cancer Center
New Haven, Connecticut, United States, 06520-8028
United States, Georgia
AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Scottish Rite Campus
Atlanta, Georgia, United States, 30342
United States, Illinois
Children's Memorial Hospital - Chicago
Chicago, Illinois, United States, 60614
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231-2410
United States, Massachusetts
Children's Hospital Boston
Boston, Massachusetts, United States, 02115
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Minnesota
Children's Hospitals and Clinics of Minnesota - Minneapolis
Minneapolis, Minnesota, United States, 55404
United States, Nevada
Sunrise Hospital and Medical Center
Las Vegas, Nevada, United States, 89109
United States, Ohio
Cleveland Clinic Taussig Cancer Center
Cleveland, Ohio, United States, 44195
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
Dallas, Texas, United States, 75390
Sponsors and Collaborators
Dana-Farber Cancer Institute
National Cancer Institute (NCI)
Investigators
Principal Investigator: Mark W. Kieran, MD, PhD Dana-Farber Cancer Institute
  More Information

Publications:
Responsible Party: Mark W. Kieran, MD, PhD, Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT00084838     History of Changes
Other Study ID Numbers: 02-294 DFCI  P30CA006516 
Study First Received: June 10, 2004
Results First Received: December 14, 2012
Last Updated: December 18, 2015
Health Authority: United States: Federal Government

Keywords provided by Dana-Farber Cancer Institute:
childhood atypical teratoid/rhabdoid tumor

Additional relevant MeSH terms:
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms
Neoplasms by Site
Nervous System Diseases
Cisplatin
Cortisol succinate
Cyclophosphamide
Cytarabine
Dactinomycin
Dexrazoxane
Doxorubicin
Hydrocortisone
Hydrocortisone 17-butyrate 21-propionate
Hydrocortisone acetate
Hydrocortisone-17-butyrate
Lenograstim
Levoleucovorin
Liposomal doxorubicin
Methotrexate
Razoxane
Temozolomide
Vincristine
Abortifacient Agents
Abortifacient Agents, Nonsteroidal
Adjuvants, Immunologic
Alkylating Agents
Anti-Bacterial Agents
Anti-Infective Agents
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on May 24, 2016