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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00025363
First received: October 11, 2001
Last updated: January 16, 2013
Last verified: January 2013
  Purpose

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


Condition Intervention Phase
Alveolar Childhood Rhabdomyosarcoma
Embryonal Childhood Rhabdomyosarcoma
Embryonal-botryoid Childhood Rhabdomyosarcoma
Previously Treated Childhood Rhabdomyosarcoma
Recurrent Childhood Rhabdomyosarcoma
Drug: vincristine sulfate
Drug: irinotecan hydrochloride
Drug: cyclophosphamide
Drug: doxorubicin hydrochloride
Drug: ifosfamide
Drug: etoposide
Drug: tirapazamine
Biological: filgrastim
Biological: sargramostim
Other: pharmacological study
Other: pharmacogenomic studies
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Groupwide Randomized Phase II Window Study of Two Different Schedules of Irinotecan in Combination With Vincristine And Pilot Assessment of Safety and Efficacy of Tirapazamine Combined With Multiagent Chemotherapy for First Relapse or Progressive Disease in Rhabdomyosarcoma and Related Tumors

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Response at week 6 of investigational window therapy (unfavorable risk patients) [ Time Frame: At week 6 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
  • Blood metabolite SN-38 levels (unfavorable risk patients) [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
  • Progression-free survival [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
  • Survival [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]

Enrollment: 150
Study Start Date: November 2001
Primary Completion Date: October 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Drug: irinotecan hydrochloride
Given IV
Other Names:
  • Campto
  • Camptosar
  • CPT-11
  • irinotecan
  • U-101440E
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • ADM
  • ADR
  • Adria
  • Adriamycin PFS
  • Adriamycin RDF
Drug: ifosfamide
Given IV
Other Names:
  • Cyfos
  • Holoxan
  • IFF
  • IFX
  • IPP
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Drug: tirapazamine
Given IV
Other Names:
  • SR 4233
  • Tirazone
  • WIN 59075
Biological: filgrastim
Given SC
Other Names:
  • G-CSF
  • Neupogen
Biological: sargramostim
Given SC
Other Names:
  • GM-CSF
  • Leukine
  • Prokine
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: pharmacogenomic studies
Correlative studies
Other Name: Pharmacogenomic Study
Other: laboratory biomarker analysis
Correlative studies
Experimental: 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.
Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Drug: irinotecan hydrochloride
Given IV
Other Names:
  • Campto
  • Camptosar
  • CPT-11
  • irinotecan
  • U-101440E
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • ADM
  • ADR
  • Adria
  • Adriamycin PFS
  • Adriamycin RDF
Drug: ifosfamide
Given IV
Other Names:
  • Cyfos
  • Holoxan
  • IFF
  • IFX
  • IPP
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Drug: tirapazamine
Given IV
Other Names:
  • SR 4233
  • Tirazone
  • WIN 59075
Biological: filgrastim
Given SC
Other Names:
  • G-CSF
  • Neupogen
Biological: sargramostim
Given SC
Other Names:
  • GM-CSF
  • Leukine
  • Prokine
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: pharmacogenomic studies
Correlative studies
Other Name: Pharmacogenomic Study
Other: laboratory biomarker analysis
Correlative studies

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   up to 20 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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: NCT00025363

Locations
United States, California
Children's Oncology Group
Arcadia, California, United States, 91006-3776
Sponsors and Collaborators
Investigators
Principal Investigator: Philip Breitfeld Children's Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00025363     History of Changes
Other Study ID Numbers: NCI-2012-01864, ARST0121, U10CA098543, CDR0000068954
Study First Received: October 11, 2001
Last Updated: January 16, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Rhabdomyosarcoma
Rhabdomyosarcoma, Embryonal
Myosarcoma
Neoplasms, Muscle Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Sarcoma
Cyclophosphamide
Ifosfamide
Isophosphamide mustard
Liposomal doxorubicin
Irinotecan
Tirapazamine
Doxorubicin
Etoposide
Vincristine
Camptothecin
Lenograstim
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists

ClinicalTrials.gov processed this record on August 21, 2014