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Combination Chemotherapy and Radiation Therapy in Treating Patients With Newly Diagnosed Rhabdomyosarcoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00354835
Recruitment Status : Unknown
Verified December 2016 by Children's Oncology Group.
Recruitment status was:  Active, not recruiting
First Posted : July 20, 2006
Results First Posted : July 25, 2017
Last Update Posted : October 27, 2020
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group

Study Description
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Brief Summary:
This randomized phase III trial is studying two different combination chemotherapy regimens to compare how well they work when given together with radiation therapy in treating patients with newly diagnosed rhabdomyosarcoma. Drugs used in chemotherapy, such as vincristine sulfate, dactinomycin, cyclophosphamide, and irinotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving combination chemotherapy together with radiation therapy may kill more tumor cells. It is not yet known which combination chemotherapy regimen is more effective when given together with radiation therapy in treating patients with rhabdomyosarcoma.

Condition or disease Intervention/treatment Phase
Adult Malignant Mesenchymoma Adult Rhabdomyosarcoma Childhood Alveolar Rhabdomyosarcoma Childhood Botryoid-Type Embryonal Rhabdomyosarcoma Childhood Embryonal Rhabdomyosarcoma Childhood Malignant Mesenchymoma Non-Metastatic Childhood Soft Tissue Sarcoma Stage I Adult Soft Tissue Sarcoma Stage II Adult Soft Tissue Sarcoma Stage III Adult Soft Tissue Sarcoma Untreated Childhood Rhabdomyosarcoma Drug: Irinotecan Hydrochloride Biological: Dactinomycin Drug: Cyclophosphamide Drug: Vincristine Sulfate Radiation: Radiation Therapy Other: Laboratory Biomarker Analysis Other: Questionnaire Administration Phase 3

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Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 481 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Randomized Study of Vincristine, Dactinomycin and Cyclophosphamide (VAC) Versus VAC Alternating With Vincristine and Irinotecan (VI) for Patients With Intermediate-Risk Rhabdomyosarcoma (RMS)
Study Start Date : December 2006
Actual Primary Completion Date : December 2014

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Active Comparator: VAC
Patients receive VAC chemotherapy comprising vincristine IV over 1 minute on day 1 of weeks 1-13, 16, 19-25, 28, 31-37, and 40; dactinomycin IV over 1-5 minutes on day 1 of weeks 1, 4, 13, 16, 19, 22, 25, 28, 31, 34, 37,and 40; and cyclophosphamide IV over 1 hour on day 1 of weeks 1, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, and 40. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4.
 Biological: Dactinomycin
Given IV
Other Name: Lyovac Cosmegen

Drug: Cyclophosphamide
Given IV

Drug: Vincristine Sulfate
Given IV
Other Names:
  • Kyocristine
  • Oncovin
  • VCR
  • Vincasar

Radiation: Radiation Therapy
Undergo radiotherapy
Other Names:
  • Cancer Radiotherapy
  • Irradiate
  • Irradiated
  • Irradiation
  • RT

Other: Laboratory Biomarker Analysis
Correlative studies

Other: Questionnaire Administration
Ancillary studies
Experimental: VAC Alternating with VI
Patients receive VAC chemotherapy alternating with VI chemotherapy comprising vincristine IV over 1 minute on day 1 of weeks 1-13, 16, 17, 19, 20, 22-26, 28, 31-34, 37, 38, and 40; dactinomycin IV over 1-5 minutes on day 1 of weeks 1, 13, 22, 28, 34, and 40; cyclophosphamide IV over 1 hour on day 1 of weeks 1,10, 13, 22, 28, 34, and 40; and irinotecan hydrochloride IV over 1 hour on days 1-5 of weeks 4, 7, 16, 19, 25, 31, and 37. Patients may also undergo radiotherapy 5 days a week for 4-6 weeks beginning in week 4.
 Drug: Irinotecan Hydrochloride
Given IV

Biological: Dactinomycin
Given IV
Other Name: Lyovac Cosmegen

Drug: Cyclophosphamide
Given IV

Drug: Vincristine Sulfate
Given IV
Other Names:
  • Kyocristine
  • Oncovin
  • VCR
  • Vincasar

Radiation: Radiation Therapy
Undergo radiotherapy
Other Names:
  • Cancer Radiotherapy
  • Irradiate
  • Irradiated
  • Irradiation
  • RT

Other: Laboratory Biomarker Analysis
Correlative studies

Other: Questionnaire Administration
Ancillary studies


Outcome Measures
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Primary Outcome Measures :
  1. Event Free Survival (EFS) [ Time Frame: 4 years ]
    Probability of no relapse, secondary malignancy, or death after 4 year in the study

  2. Response Rate (RR) [ Time Frame: Reporting Period 1 (Weeks 1 - 15) ]
    Proportion of patients with complete or partial response. Complete Response (CR): Complete disappearance of the tumor confirmed at > 4 weeks; Partial Response (PR): At least 64% decrease in volume compared to the baseline; Overall Response (OR) = CR + PR.

  3. Overall Survival (OS) [ Time Frame: 4 years ]
    Probability of being alive after 4 years in the study.


Secondary Outcome Measures :
  1. Event Free Survival (EFS) Probability VAC and Early (Week 4) Radiotherapy Compared to Delayed (Week 10) Radiotherapy, Using IRSIV for Historic Comparison [ Time Frame: 4 years ]
    Compare 4-year EFS using eligible participants only to the historical rate of 0.65 with IRSI-V. The 4-year EFS is probability of no relapse, secondary malignancy, or death after 4 years in the study. The Delayed (Week 10) Radiotherapy is from IRSI-V, and the number of participants of IRSI-V is unknown, but we have the rate of 0.65.

  2. Local Failure [ Time Frame: 2 years ]
    Compare 2-year local failure rate to the historical rate of 0.13 with IRSI-V. The Delayed (Week 10) Radiotherapy is from IRSI-V, and the number of participants of IRSI-V is unknown, but we have the rate of 0.13.

  3. Overall Survival (OS) Probability VAC and Early (Week 4) Radiotherapy Compared to Delayed (Week 10) Radiotherapy, Using IRSIV for Historic Comparison [ Time Frame: 4 years ]
    Compare 4-year OS using eligible participants only to the historical rate of 0.70 with IRSI-V. The 4-year OS is probability of being alive after 4 years in the study. The Delayed (Week 10) Radiotherapy is from IRSI-V, and the number of participants of IRSI-V is unknown, but we have the rate of 0.70.

  4. Incidence of Toxicity [ Time Frame: Up to 15 weeks ]
    Grade 3 or 4 nausea, diarrhea, dehydration, radiation dermatitis, mucositis due to radiation. Severe and undesirable adverse event is considered as grade 3; Life-threatening or disabling adverse event is grade 4. Grade 4 is worse than grade 3.

  5. Acute and Late Effects of VAC as Delivered on This Study to D9803 VAC [ Time Frame: Up to 43 weeks ]
    The toxicity rates will be estimated for each phase and course of treatment, and will be compared to the fixed rates under D9803 using one-sided lower confidence intervals for a single proportion without adjustment for multiple comparisons.

  6. Compare Event Free Survival (EFS) With Respect to the Level of % Change in FDG PET Maximum Standard Uptake Value (SUVmax) at Week 4 [ Time Frame: 4 years ]
    4-year EFS (probability of no relapse, secondary malignancy, or death after 4 years in the study).

  7. Compare Event Free Survival (EFS) With Respect to the Level of % Change in FDG PET Maximum Standard Uptake Value (SUVmax) at Week 15 [ Time Frame: 4 years ]
    4-year EFS (probability of no relapse, secondary malignancy, or death after 4 years in the study)

  8. Incidence of Toxicity Related to VI Treatment in Patients With UGT1A1 Genotype [ Time Frame: Weeks 4-9 (the first exposure to VI) ]
    Severe and undesirable adverse event is considered as grade 3; Life-threatening or disabling adverse event is grade 4. Grade 4 is worse than grade 3.

  9. Toxicity With CYP2B6 Genotypes [ Time Frame: During the study ]
    Incidence of toxicity related to VAC treatment in patients with CYP2B6 genotypes.

  10. Toxicity With GSTA1 and CYP2C9 Genotypes [ Time Frame: During the study ]
    Incidence of toxicity related to VAC treatment in patients with GSTA1 and CYP2C9 genotypes.

  11. Event Free Survival (EFS) by PAX Status [ Time Frame: 4 years ]
  12. Incidence of Bladder Dysfunction [ Time Frame: 3-6 years after enrollment ]
    Number of patients with a summary score greater than 8.5


Eligibility Criteria
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Ages Eligible for Study:   up to 49 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with newly diagnosed embryonal RMS, botryoid or spindle cell variants of embryonal RMS, ectomesenchymoma, or alveolar RMS are eligible for this study
  • Enrollment on COG-D9902 to confirm local histologic diagnosis with central pathology review is required for all patients
  • Patients may be enrolled on ARST0531 and start protocol treatment prior to receipt of central pathology review results

  • Patient must have Intermediate-risk RMS defined as:

    • Embryonal, botryoid, or spindle cell RMS, or ectomesenchymoma: stage 2 or 3 and group III OR
    • Alveolar RMS: stage 1-3 and group I-III
  • Staging ipsilateral retroperitoneal lymph node dissection (SIRLND) is required for all patients >= 10 years of age with paratesticular tumors and for patients < 10 years with clinically or radiographically involved lymph nodes (except when extensive lymph node involvement, defined as two or more lymph nodes > 2 cm in dimension, is identified by imaging studies)
  • Regional lymph node sampling or sentinel lymph node procedure is required for histologic evaluation in patients with extremity tumors
  • Clinically or radiographically enlarged nodes should be sampled for histologic evaluation
  • Detection of metastasis by optional FDG PET (not required for study enrollment); FDG PET may detect abnormalities suggestive of metastasis not identified by bone scan, computed tomography (CT), or bone marrow aspiration/biopsy; the prognostic significance of FDG PET-detected abnormalities is not clear; FDG PET-detected abnormalities MUST be confirmed to be metastases by an additional imaging modality (such as magnetic resonance imaging [MRI] or CT) OR pathologic confirmation; unless FDG PET abnormalities are confirmed by another imaging modality or biopsy, FDG PET abnormalities will NOT be considered evidence of metastasis
  • Patients must have a performance status of 0, 1, or 2; the Lansky performance score should be used for patients < 16 years and the Karnofsky performance score for patients >= 16 years
  • Patients who have received prior chemotherapy (excluding steroids) or radiation therapy, except for patients transferring from ARST0331 (low-risk study), are not eligible

  • Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 ml/min/1.73 m^2 or a serum creatinine based on age/gender as follows:

    • 1 month to < 6 months: 0.4 mg/dL
    • 6 months to < 1 year: 0.5 mg/dL
    • 1 to < 2 years: 0.6 mg/dL
    • 2 to < 6 years: 0.8 mgt/dL
    • 6 to < 10 years: 1 mg/dL
    • 10 to < 13 years: 1.2 mg/dL
    • 13 to < 16 years: 1.5 mg/dL (males) or 1.4 mg/dL (females)
    • >= 16 years: 1.7 mg/dL (males) or 1.4 mg/dL (females)
  • Patients with urinary tract obstruction by tumor must meet the renal function criteria AND must have unimpeded urinary flow established via decompression of the obstructed portion of the urinary tract
  • Total bilirubin =< 1.5 x upper limit of normal for age
  • Peripheral absolute neutrophil count (ANC) >= 750/uL
  • Platelet count >= 75,000/uL (transfusion independent)
  • No evidence of uncontrolled infection
  • Patients must be able to undergo radiation therapy, if necessary, as specified in the protocol
  • Female patients of childbearing potential must have a negative pregnancy test
  • Female patients who are breast feeding must agree to stop breast feeding
  • Sexually active patients of childbearing potential must be willing to use effective contraception during therapy and for at least 1 month after treatment is completed
  • All patients and/or their parents or legal guardians must sign a written informed consent
  • All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00354835


Locations
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Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Douglas Hawkins, MD Children's Oncology Group
More Information
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Additional Information:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00354835    
Other Study ID Numbers: ARST0531
NCI-2009-00427 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
COG-ARST0531 ( Other Identifier: Children's Oncology Group )
CDR0000487560 ( Other Identifier: ClinicalTrials.gov )
ARST0531 ( Other Identifier: Children's Oncology Group )
ARST0531 ( Other Identifier: CTEP )
U10CA098543 ( U.S. NIH Grant/Contract )
U10CA180886 ( U.S. NIH Grant/Contract )
First Posted: July 20, 2006    Key Record Dates
Results First Posted: July 25, 2017
Last Update Posted: October 27, 2020
Last Verified: December 2016
Additional relevant MeSH terms:
Layout table for MeSH terms
Sarcoma
Rhabdomyosarcoma
Mesenchymoma
Rhabdomyosarcoma, Alveolar
Rhabdomyosarcoma, Embryonal
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Myosarcoma
Neoplasms, Muscle Tissue
Neoplasms, Complex and Mixed
Dactinomycin
Cyclophosphamide
Irinotecan
Vincristine
 Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents