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NCT00025363 · CITED IN SOURCE DOCUMENTS

Comparison of Chemotherapy Regimens in Treating Children With Relapsed or Progressive Rhabdomyosarcoma

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase
PHASE2
Status at capture
COMPLETED
Registry last update
2013-01-17

Randomized phase II trial to compare the effectiveness of different combination chemotherapy regimens in treating children who have rhabdomyosarcoma. Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells

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.

No posted result sections were captured. Registered plans do not establish that a treatment works.

Who could take part
eligibility Criteria
Inclusion Criteria: * Histologically confirmed rhabdomyosarcoma, undifferentiated sarcoma, or ectomesenchymoma * First relapse or first occurrence of disease progression * Unfavorable-risk patients eligible for study window therapy with irinotecan and vincristine meeting the following criteria: * Unfavorable risk defined by any of the following: * Embryonal histology with stage I or group I at initial diagnosis with distant recurrence or with local or regional recurrence after prior cyclophosphamide * Embryonal histology with initial stage II, III, or IV or group II, III, or IV with any relapse pattern * Alveolar histology with any stage or group at initial diagnosis * At least unidimensionally measurable disease * No prior irinotecan * Bone marrow must not be only site of relapse * Unfavorable-risk patients ineligible for study window therapy with irinotecan meeting the following criteria: * Either no measurable disease OR patient received prior irinotecan * Bone marrow as only site of relapse allowed * Favorable-risk patients meeting the following criteria: * Initial botryoid histology (any stage, any group, or any pattern of relapse) * Embryonal histology if either stage I or group I (with either local or regional recurrence) * No prior cyclophosphamide * No CNS metastases * Performance status - ECOG 0-2 * Performance status - Zubrod 0-2 * At least 2 months * Absolute neutrophil count at least 750/mm\^3 * Platelet count at least 75,000/mm\^3 (transfusion independent) * Hemoglobin at least 10.0 g/dL (red blood cell transfusion allowed) * Bilirubin no greater than 1.5 times normal * SGPT less than 2.5 times normal * Creatinine no greater than 1.5 times normal * Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min * Shortening fraction at least 27% by echocardiogram * Ejection fraction at least 50% by MUGA * No prior ischemic heart disease * Seizure disorder allowed if well controlled by anticonvulsants * No CNS toxicity greater than grade 2 * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No prior myeloablative therapy with stem cell transplantation * At least 1 week since prior antineoplastic biologic agent * At least 1 week since prior growth factor(s) * Recovered from prior immunotherapy * No concurrent immunomodulating agents * See Disease Characteristics * See Biologic therapy * No more than 1 prior chemotherapy regimen * No prior doxorubicin or daunorubicin * At least 2 weeks since prior myelosuppressive chemotherapy (4 weeks for nitrosoureas) and recovered * No other concurrent anticancer chemotherapy * Concurrent corticosteroid therapy allowed * At least 2 weeks since prior small-port radiotherapy. * At least 6 months since prior radiotherapy to 50% or more of pelvis * At least 6 weeks since other prior substantial radiotherapy to bone marrow * Recovered from prior radiotherapy * Concurrent radiotherapy to localized painful lesions allowed provided at least 1 measurable lesion is not irradiated * No concurrent intensity-modulated radiotherapy
healthy Volunteers
false
maximum Age
20 Years
sex
ALL
std Ages
  1. CHILD
  2. ADULT
Treatment arms and interventions
arm Groups
  1. description
    Patients receive vincristine IV on days 1 and 8 and irinotecan IV over 1 hour on days 1-5 and 8-12. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.
    intervention Names
    1. Drug: vincristine sulfate
    2. Drug: irinotecan hydrochloride
    3. Drug: cyclophosphamide
    4. Drug: doxorubicin hydrochloride
    5. Drug: ifosfamide
    6. Drug: etoposide
    7. Drug: tirapazamine
    8. Biological: filgrastim
    9. Biological: sargramostim
    10. Other: pharmacological study
    11. Other: pharmacogenomic studies
    12. Other: laboratory biomarker analysis
    label
    Arm I
    type
    EXPERIMENTAL
  2. description
    Patients receive vincristine IV on days 1 and 8 and irinotecan IV over 1 hour on days 1-5. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.
    intervention Names
    1. Drug: vincristine sulfate
    2. Drug: irinotecan hydrochloride
    3. Drug: cyclophosphamide
    4. Drug: doxorubicin hydrochloride
    5. Drug: ifosfamide
    6. Drug: etoposide
    7. Drug: tirapazamine
    8. Biological: filgrastim
    9. Biological: sargramostim
    10. Other: pharmacological study
    11. Other: pharmacogenomic studies
    12. Other: laboratory biomarker analysis
    label
    Arm II
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. Arm I
    2. Arm II
    description
    Given IV
    name
    vincristine sulfate
    other Names
    1. leurocristine sulfate
    2. VCR
    3. Vincasar PFS
    type
    DRUG
  2. arm Group Labels
    1. Arm I
    2. Arm II
    description
    Given IV
    name
    irinotecan hydrochloride
    other Names
    1. Campto
    2. Camptosar
    3. CPT-11
    4. irinotecan
    5. U-101440E
    type
    DRUG
  3. arm Group Labels
    1. Arm I
    2. Arm II
    description
    Given IV
    name
    cyclophosphamide
    other Names
    1. CPM
    2. CTX
    3. Cytoxan
    4. Endoxan
    5. Endoxana
    type
    DRUG
  4. arm Group Labels
    1. Arm I
    2. Arm II
    description
    Given IV
    name
    doxorubicin hydrochloride
    other Names
    1. ADM
    2. ADR
    3. Adria
    4. Adriamycin PFS
    5. Adriamycin RDF
    type
    DRUG
  5. arm Group Labels
    1. Arm I
    2. Arm II
    description
    Given IV
    name
    ifosfamide
    other Names
    1. Cyfos
    2. Holoxan
    3. IFF
    4. IFX
    5. IPP
    type
    DRUG
  6. arm Group Labels
    1. Arm I
    2. Arm II
    description
    Given IV
    name
    etoposide
    other Names
    1. EPEG
    2. VP-16
    3. VP-16-213
    type
    DRUG
  7. arm Group Labels
    1. Arm I
    2. Arm II
    description
    Given IV
    name
    tirapazamine
    other Names
    1. SR 4233
    2. Tirazone
    3. WIN 59075
    type
    DRUG
  8. arm Group Labels
    1. Arm I
    2. Arm II
    description
    Given SC
    name
    filgrastim
    other Names
    1. G-CSF
    2. Neupogen
    type
    BIOLOGICAL
  9. arm Group Labels
    1. Arm I
    2. Arm II
    description
    Given SC
    name
    sargramostim
    other Names
    1. GM-CSF
    2. Leukine
    3. Prokine
    type
    BIOLOGICAL
  10. arm Group Labels
    1. Arm I
    2. Arm II
    description
    Correlative studies
    name
    pharmacological study
    other Names
    1. pharmacological studies
    type
    OTHER
  11. arm Group Labels
    1. Arm I
    2. Arm II
    description
    Correlative studies
    name
    pharmacogenomic studies
    other Names
    1. Pharmacogenomic Study
    type
    OTHER
  12. arm Group Labels
    1. Arm I
    2. Arm II
    description
    Correlative studies
    name
    laboratory biomarker analysis
    type
    OTHER
Study design
allocation
RANDOMIZED
intervention Model
PARALLEL
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
150
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. measure
    Response at week 6 of investigational window therapy (unfavorable risk patients)
    time Frame
    At week 6
  2. measure
    Incidence of DLT when tirapazamine is given in combination with cyclophosphamide and doxorubicin, graded according to the NCI CTC v 2.0
    time Frame
    Up to 6 years
secondary Outcomes
  1. measure
    Incidence of toxicities associated with the two administration schedules of irinotecan in combination with vincristine, graded according to the NCI CTC v 2.0 (unfavorable risk patients)
    time Frame
    Up to 6 years
  2. measure
    Blood metabolite SN-38 levels (unfavorable risk patients)
    time Frame
    Up to 6 years
  3. measure
    Progression-free survival
    time Frame
    Up to 6 years
  4. measure
    Survival
    time Frame
    Up to 6 years
Full study description
brief Summary
Randomized phase II trial to compare the effectiveness of different combination chemotherapy regimens in treating children who have rhabdomyosarcoma. Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells
detailed Description
OBJECTIVES: I. Compare response rate in children with relapsed or progressive rhabdomyosarcoma, undifferentiated sarcoma, or ectomesenchymoma treated with 2 different schedules of irinotecan and vincristine in an upfront phase II window. II. Determine the progression-free and overall survival of patients treated with multiagent chemotherapy. III. Determine the toxic effects of tirapazamine, doxorubicin, and cyclophosphamide in these patients. IV. Determine the toxic effects of irinotecan and vincristine in these patients. V. Determine whether conversion of irinotecan to its active metabolite SN-38 predicts tumor response in these patients. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to risk status and window therapy eligibility (unfavorable risk and eligible vs unfavorable risk and ineligible vs favorable risk). UNFAVORABLE-RISK PATIENTS ELIGIBLE FOR WINDOW THERAPY: Patients are stratified according to prior topotecan (yes vs no). These patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive vincristine IV on days 1 and 8 and irinotecan IV over 1 hour on days 1-5 and 8-12. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive vincristine IV on days 1 and 8 and irinotecan IV over 1 hour on days 1-5. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients in both arms with partial response (PR) or complete response (CR) receive 5 additional courses of irinotecan and vincristine on the previous schedule. In addition, patients with PR or CR also receive cyclophosphamide/doxorubicin (CD) and ifosfamide/etoposide (IE) chemotherapy. CD/IE CHEMOTHERAPY: Patients receive cyclophosphamide IV over 1 hour and doxorubicin IV over 15-30 minutes on day 1 of weeks 7, 16, 28, 37, and 40. Patients also receive ifosfamide IV over 1 hour and etoposide IV over 1 hour on days 1-5 of weeks 10, 19, 22, 31, and 43. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients with no response or progressive disease on arm I or II proceed to tirapazamine/cyclophosphamide/doxorubicin (TCD) and ifosfamide/etoposide (IE) chemotherapy. TCD/IE CHEMOTHERAPY: Patients receive tirapazamine IV over 2 hours, cyclophosphamide IV over 1 hour, and doxorubicin IV over 15-30 minutes on day 1 of weeks 7, 10, 16, 25, and 34. Patients also receive ifosfamide IV over 1 hour and etoposide IV over 1 hour on days 1-5 of weeks 13, 19, 22, 28, 31, and 37. PATIENTS WITH UNFAVORABLE RISK AND INELIGIBLE FOR WINDOW THERAPY: Patients receive tirapazamine IV over 2 hours, cyclophosphamide IV over 1 hour, and doxorubicin IV over 15-30 minutes on day 1 of weeks 1, 4, 10, 19, and 28. Patients also receive ifosfamide IV over 1 hour and etoposide IV over 1 hour on days 1-5 of weeks 7, 13, 16, 22, 25, and 31. Patients also receive filgrastim (G-CSF) or sargramostim (GM-CSF) subcutaneously (SC) beginning 1 day after each course of chemotherapy and continuing until blood counts recover. Treatment continues in the absence of disease progression or unacceptable toxicity. PATIENTS WITH FAVORABLE RISK: Patients receive cyclophosphamide IV over 1 hour and doxorubicin IV over 15-30 minutes on day 1 of weeks 1, 4, 10, 19, and 28. Patients also receive ifosfamide IV over 1 hour and etoposide IV over 1 hour on days 1-5 of weeks 7, 13, 16, 22, 25, and 31. Patients also receive G-CSF or GM-CSF SC beginning 1 day after each course of chemotherapy and continuing until blood counts recover. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients are followed every 2 months for 1 year, every 4 months for 2 years, and then annually thereafter.
Source references
Source notices and limitations
    Discovery and provenance
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        36">36</a>] <div class="pdq-content-list"><ol id="_1957" class="lower-alpha"><li>A COG prospective, randomized, up-front window trial, <a href="/clinicaltrials/NCT00025363">COG-ARST0121</a>, compared VI (20 mg/m<span class="sup">2</span>/d) daily &#215; 5 days for 4 weeks per 6-week treatment cycle (Regimen 1A) and irinotecan (50
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      Childhood Rhabdomyosarcoma Treatment (PDQ®)–Health Professional Version
      source update dates
      1. context
        Updated: April 11, 2025
        datetime
        2025-04-11T12:00:00Z
        display
        April 11, 2025

    Preserved source evidence · Not medical advice