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NCT00084838 · REGISTRY CONDITION SEARCH

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

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase
PHASE2
Status at capture
COMPLETED
Registry last update
2015-12-24

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

2-yr Overall Survival

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outcome · POSTED

Pre-Radiation Therapy Chemotherapeutic Response

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outcome · POSTED

Grade 3/4 Events

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outcome · POSTED

Grade 3-4 Auditory/Hearing Events

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outcome · POSTED

Grade 3-4 Blood/Bone Marrow Events

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outcome · POSTED

Grade 3-4 Gastrointestinal Events

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outcome · POSTED

Grade 3-4 Metabolic/Laboratory Events

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outcome · POSTED

Grade 3-4 Infection/Febrile Neutropenia Events

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outcome · POSTED

Grade 3-4 Neurology Events

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outcome · POSTED

Grade 3-4 Pain Events

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outcome · POSTED

Grade 3-4 Constitutional Events

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outcome · POSTED

Grade 3-4 Muscloskeletal Events

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outcome · POSTED

Grade 3-4 Hepatic Events

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outcome · POSTED

Grade 3-4 Cardiovascular Events

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outcome · POSTED

Grade 3-4 Pulmonary Events

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outcome · POSTED

Grade 3-4 Renal/Genitourinary Events

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outcome · POSTED

Grade 3-4 Dermatology Events

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outcome · POSTED

Grade 3-4 Hemorrhage Events

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outcome · POSTED

Grade 3-4 Allergy/Immunology

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part
eligibility 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
healthy Volunteers
false
maximum Age
18 Years
sex
ALL
std Ages
  1. CHILD
  2. ADULT
Treatment arms and interventions
arm Groups
  1. description
    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.
    intervention Names
    1. Biological: filgrastim
    2. Drug: cisplatin
    3. Drug: cyclophosphamide
    4. Drug: cytarabine
    5. Drug: dexrazoxane hydrochloride
    6. Drug: doxorubicin hydrochloride
    7. Drug: etoposide
    8. Drug: leucovorin calcium
    9. Drug: methotrexate
    10. Drug: temozolomide
    11. Drug: therapeutic hydrocortisone
    12. Drug: vincristine sulfate
    label
    Multi-agent Intrathecal and Systemic CT with RT (mod IRS III)
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. Multi-agent Intrathecal and Systemic CT with RT (mod IRS III)
    name
    filgrastim
    other Names
    1. filgrastim XM02
    2. G-CSF
    type
    BIOLOGICAL
  2. arm Group Labels
    1. Multi-agent Intrathecal and Systemic CT with RT (mod IRS III)
    name
    cisplatin
    other Names
    1. CACP
    2. cis-DDP
    3. cis-diamminedichloro platinum (II)
    4. cis-diamminedichloroplatinum
    5. Cis-dichloroammine Platinum (II)
    6. Cismaplat
    7. Platinol
    type
    DRUG
  3. arm Group Labels
    1. Multi-agent Intrathecal and Systemic CT with RT (mod IRS III)
    name
    cyclophosphamide
    other Names
    1. Ciclofosfamida
    2. Ciclofosfamide
    3. Claphene
    4. CP monohydrate
    5. CPM
    6. Cyclophospham
    7. Cyclophosphamid monohydrate
    8. Cyclophosphamidum
    9. Cyclophosphan
    10. Cyclophosphanum
    11. Cytophosphane
    12. Mitoxan
    type
    DRUG
  4. arm Group Labels
    1. Multi-agent Intrathecal and Systemic CT with RT (mod IRS III)
    name
    cytarabine
    other Names
    1. arabinofuranosylcytosine
    2. arabinosylcytosine
    3. aracytidine
    4. beta-cytosine arabinoside
    5. cytarabine hydrochloride
    6. cytarabinum
    7. cytosine arabinoside
    8. cytosine arabinosine hydrochloride
    9. Cytosar-U
    10. Tarabine PFS
    type
    DRUG
  5. arm Group Labels
    1. Multi-agent Intrathecal and Systemic CT with RT (mod IRS III)
    name
    dexrazoxane hydrochloride
    other Names
    1. Totect
    2. Zinecard
    type
    DRUG
  6. arm Group Labels
    1. Multi-agent Intrathecal and Systemic CT with RT (mod IRS III)
    name
    doxorubicin hydrochloride
    other Names
    1. Adriamycin PFS
    2. Adriamycin RDF
    type
    DRUG
  7. arm Group Labels
    1. Multi-agent Intrathecal and Systemic CT with RT (mod IRS III)
    name
    etoposide
    other Names
    1. VP-16
    type
    DRUG
  8. arm Group Labels
    1. Multi-agent Intrathecal and Systemic CT with RT (mod IRS III)
    name
    leucovorin calcium
    other Names
    1. folinate calcium
    2. folinic acid
    type
    DRUG
  9. arm Group Labels
    1. Multi-agent Intrathecal and Systemic CT with RT (mod IRS III)
    name
    methotrexate
    type
    DRUG
  10. arm Group Labels
    1. Multi-agent Intrathecal and Systemic CT with RT (mod IRS III)
    name
    temozolomide
    other Names
    1. Temodar, Methazolastone, Temodal, TMZ, CCRG-81045
    type
    DRUG
  11. arm Group Labels
    1. Multi-agent Intrathecal and Systemic CT with RT (mod IRS III)
    name
    therapeutic hydrocortisone
    type
    DRUG
  12. arm Group Labels
    1. Multi-agent Intrathecal and Systemic CT with RT (mod IRS III)
    name
    vincristine sulfate
    other Names
    1. leurocristine sulfate
    2. Vincasar PFS
    type
    DRUG
Study design
allocation
NA
intervention Model
SINGLE_GROUP
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
25
type
ACTUAL
Registered outcome plans (not posted results)
other Outcomes
  1. description
    All Grade 3-4 events based on CTCAEv2 as reported on case report forms.
    measure
    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.
  2. description
    All Grade 3-4 Auditory/Hearing events based on CTCAEv2 as reported on case report forms.
    measure
    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.
  3. description
    All Grade 3-4 Blood/Bone Marrow events based on CTCAEv2 as reported on case report forms. Arm Name
    measure
    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.
  4. description
    All Grade 3-4 Gastrointestinal events based on CTCAEv2 as reported on case report forms.
    measure
    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.
  5. description
    All Grade 3-4 Metabolic/Laboratory events based on CTCAEv2 as reported on case report forms.
    measure
    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.
  6. description
    All Grade 3-4 Infection/Febrile Neutropenia events based on CTCAEv2 as reported on case report forms.
    measure
    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.
  7. description
    All Grade 3-4 Neurology events based on CTCAEv2 as reported on case report forms.
    measure
    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.
  8. description
    All Grade 3-4 Pain events based on CTCAEv2 as reported on case report forms.
    measure
    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.
  9. description
    All Grade 3-4 Constitutional events based on CTCAEv2 as reported on case report forms.
    measure
    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.
  10. description
    All Grade 3-4 Muscloskeletal events based on CTCAEv2 as reported on case report forms.
    measure
    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.
  11. description
    All Grade 3-4 Hepatic events based on CTCAEv2 as reported on case report forms.
    measure
    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.
  12. description
    All Grade 3-4 Cardiovascular events based on CTCAEv2 as reported on case report forms.
    measure
    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.
primary Outcomes
  1. description
    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.
    measure
    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.
secondary Outcomes
  1. description
    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.
    measure
    Pre-Radiation Therapy Chemotherapeutic Response
    time Frame
    Assessed at study entry and pre-RT/post-CT at week 7.
Full study description
brief Summary
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.
detailed Description
OBJECTIVES: 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.
Source references
references
  1. citation
    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.
    pmid
    19064966
    type
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Source notices and limitations
    Discovery and provenance
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    Preserved source evidence · Not medical advice