Chemotherapy Combined With Radiation Therapy for Newly Diagnosed CNS AT/RT
NCT ID: NCT00084838
Last Updated: 2015-12-24
Study Results
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
PHASE2
25 participants
INTERVENTIONAL
2003-02-28
2013-03-31
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
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.
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Primary
* Determine the efficacy of intensive systemic and intrathecal chemotherapy and radiotherapy, in terms of medial survival, in children with newly diagnosed central nervous system atypical teratoid/rhabdoid tumors in comparison with historical outcomes from prior trials.
Secondary
* Determine the toxicity profile and tolerability of this regimen in these patients.
* Determine the chemosensitivity of these patients' tumors by Magnetic Resonance Imaging (MRI) after an attempt at maximum surgical resection after 2 courses of this regimen.
* Determine the predictive value of the INI-1 gene mutation in determining prognosis by comparing tumor samples from patients with vs without this mutation treated with this regimen.
STATISTICAL DESIGN: This was a single arm design evaluating median overall survival. The chosen historical control estimate of 7 months was based on 2 large multi-institutional studies in a similar setting and the alternative of 20.5 months based on a DFCI pilot study. There was 90% power to detect this improvement assuming 1-sided 0.10 alpha and 17 eligible patients. Sample size (n=20 patients) was inflated for expected 10-15% ineligible rate.
TREATMENT: Induction chemotherapy was required to be initiated within 50 days of the most definitive surgery.
* Central Nervous System (CNS)/intrathecal therapy: All patients with M0 disease receive triple intrathecal (IT) chemotherapy comprising methotrexate (MTX), cytarabine, and hydrocortisone on day 1 of weeks 1, 2, 4, 7, 13, 19, 27, 33, 39, 45, and 51 followed by oral or intravenous (IV) leucovorin calcium given 24 hours after each MTX dose. Patients with initially positive cerebrospinal fluid (CSF) cytology (M+) receive triple IT chemotherapy weekly until 2 consecutive CSF samples are negative for malignant cells.
* Pre-irradiation induction therapy (weeks 1-6): Patients receive vincristine IV on day 1 of weeks 1-6; cisplatin IV over 8 hours on day 1 and doxorubicin IV continuously over 48 hours beginning on day 2 of weeks 1 and 4; cyclophosphamide IV continuously over 72 hours beginning on day 2 of week 1; etoposide IV over 1 hour on days 1-3 of week 4; and filgrastim (G-CSF) subcutaneously (SC) beginning on day 6 of week 1 and day 4 of week 4 and continuing until blood counts recover.
* Induction chemoradiotherapy (weeks 7-12): Patients receive vincristine IV on day 1 of weeks 7-12; cisplatin IV over 8 hours on day 1, cyclophosphamide IV over 1 hour on day 2, etoposide IV over 1 hour on days 1-3 of weeks 7 and 10; and granulocyte-colony stimulating factor (G-CSF) subcutaneous (SC) daily beginning on day 4 of weeks 7 and 10 and continuing until blood counts recover. Patients with M0 disease and patients under 3 years of age with M+ disease undergo radiotherapy to the primary tumor daily on weeks 7-12. Patients 3 years of age and over with M+ disease undergo craniospinal irradiation (CSI) daily on weeks 7-12 until negative cerebral spinal fluid (CSF) cytology is achieved.
* Post-radiation induction therapy (weeks 13-18): Patients receive vincristine IV on day 1 of weeks 13 and 16; doxorubicin and cyclophosphamide as in pre-irradiation induction therapy beginning on day 1 of week 13; cyclophosphamide IV over 1 hour on days 1-3 of week 16; dactinomycin IV on days 1-5 of week 16; and G-CSF SC daily beginning on day 6 of weeks 13 and 16 and continuing until blood counts recover.
* Maintenance chemotherapy (weeks 19-42): Patients receive vincristine IV on day 1 of weeks 27, 33, and 39 and days 1 and 5 of weeks 30, 36, and 42; doxorubicin and cyclophosphamide as in pre-irradiation induction beginning on day 1 of weeks 27 and 33; doxorubicin IV over 15 minutes and dexrazoxane (DX) IV over 15 minutes on days 1 and 2 of week 39; cyclophosphamide IV over 1 hour on days 1-3 of weeks 30, 36, 39, and 42; dactinomycin IV on days 1-5 of weeks 30, 36, and 42 and on day 1 of weeks 19 and 23; oral temozolomide on days 1-5 of weeks 19 and 23; and G-CSF SC daily beginning on day 6 of weeks 19, 23, 30, 36, and 42, day 5 of weeks 27 and 33, and day 4 of week 39 and continuing until blood counts recover.
* Doxorubicin continuation therapy (for patients not receiving CSI and mediastinal radiotherapy)(weeks 45-51): Patients receive vincristine IV on day 1 of weeks 45, 48, and 51 and day 5 of week 48; doxorubicin IV over 15 minutes and DX IV over 15 minutes on days 1 and 2 of weeks 45 and 51; cyclophosphamide IV over 1 hour on days 1-3 of weeks 45, 48, and 51; dactinomycin IV on days 1-5 of week 48; and G-CSF SC daily beginning on day 4 of weeks 45 and 51 and day 6 of week 48 and continuing until blood counts recover.
* Non-doxorubicin continuation therapy (for patients receiving CSI or mediastinal radiotherapy)(weeks 45-51): Patients receive cyclophosphamide and G-CSF as in doxorubicin continuation therapy; vincristine IV on days 1 and 5 of weeks 45, 48, and 51; and dactinomycin IV on days 1-5 of weeks 45, 48, and 51.
Treatment continues in the absence of disease progression or unacceptable toxicity.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Keywords
Explore important study keywords that can help with search, categorization, and topic discovery.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
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.
filgrastim
cisplatin
cyclophosphamide
cytarabine
dexrazoxane hydrochloride
doxorubicin hydrochloride
etoposide
leucovorin calcium
methotrexate
temozolomide
therapeutic hydrocortisone
vincristine sulfate
radiation therapy
Dactinomycin
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
filgrastim
cisplatin
cyclophosphamide
cytarabine
dexrazoxane hydrochloride
doxorubicin hydrochloride
etoposide
leucovorin calcium
methotrexate
temozolomide
therapeutic hydrocortisone
vincristine sulfate
radiation therapy
Dactinomycin
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* 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
18 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
National Cancer Institute (NCI)
NIH
Dana-Farber Cancer Institute
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Mark W. Kieran, MD, PhD
Principal Investigator
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Mark W. Kieran, MD, PhD
Role: PRINCIPAL_INVESTIGATOR
Dana-Farber Cancer Institute
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Stanford Cancer Center
Stanford, California, United States
Yale Cancer Center
New Haven, Connecticut, United States
AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Scottish Rite Campus
Atlanta, Georgia, United States
Children's Memorial Hospital - Chicago
Chicago, Illinois, United States
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States
Children's Hospital Boston
Boston, Massachusetts, United States
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, United States
Children's Hospitals and Clinics of Minnesota - Minneapolis
Minneapolis, Minnesota, United States
Sunrise Hospital and Medical Center
Las Vegas, Nevada, United States
Cleveland Clinic Taussig Cancer Center
Cleveland, Ohio, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
Dallas, Texas, United States
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
Chi SN, Zimmerman MA, Yao X, Cohen KJ, Burger P, Biegel JA, Rorke-Adams LB, Fisher MJ, Janss A, Mazewski C, Goldman S, Manley PE, Bowers DC, Bendel A, Rubin J, Turner CD, Marcus KJ, Goumnerova L, Ullrich NJ, Kieran MW. Intensive multimodality treatment for children with newly diagnosed CNS atypical teratoid rhabdoid tumor. J Clin Oncol. 2009 Jan 20;27(3):385-9. doi: 10.1200/JCO.2008.18.7724. Epub 2008 Dec 8.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
02-294 DFCI
Identifier Type: -
Identifier Source: org_study_id