Vincristine, Dactinomycin, and Cyclophosphamide With or Without Radiation Therapy in Treating Patients With Newly Diagnosed Low-Risk Rhabdomyosarcoma

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00075582
First received: January 9, 2004
Last updated: March 6, 2014
Last verified: March 2014
  Purpose

This phase III trial is studying how well combination chemotherapy and radiation therapy work in treating patients with newly diagnosed low-risk rhabdomyosarcoma. Drugs used in chemotherapy, such as vincristine, dactinomycin, and cyclophosphamide, 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. Combining chemotherapy with radiation therapy may kill more tumor cells. It is not yet known which treatment regimen is more effective in treating low-risk rhabdomyosarcoma.


Condition Intervention Phase
Adult Rhabdomyosarcoma
Embryonal Childhood Rhabdomyosarcoma
Embryonal-botryoid Childhood Rhabdomyosarcoma
Previously Untreated Childhood Rhabdomyosarcoma
Procedure: conventional surgery
Drug: dactinomycin
Drug: cyclophosphamide
Drug: vincristine sulfate
Radiation: radiation therapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Vincristine, Dactinomycin, and Lower Doses of Cyclophosphamide With or Without Radiation Therapy for Patients With Newly Diagnosed Low-Risk Embryonal/Botryoid/Spindle Cell Rhabdomyosarcoma

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • Estimated Percentage of Patients Failure Free at 5 Years (95% Confidence Interval) [ Time Frame: Five years from study enrollment ] [ Designated as safety issue: No ]
    Failure-free survival: Time to disease recurrence or death as a first event.

  • FFS for Patients With Stage 1, Clinical Group IIB or C (Node Positive) or Stage 2 Group I or Stage 2 Group II Disease Treated With Subset 1 Therapy Failure-free at 5 Years (95% Confidence Interval) [ Time Frame: Five years from study enrollment ] [ Designated as safety issue: No ]
    Estimated percentage of patients with Stage I, Clinical Group IIB or C (Node Positive) or Stage 2 Group I or Stage 2 Group II disease failure free at 5 years.

  • Estimated Percentage of Patients With Low-risk Rhabdomyosarcoma Treated With Subset 2 Therapy Failure Free at 5 Years (95% Confidence Interval). [ Time Frame: 5 years from study enrollment ] [ Designated as safety issue: No ]
    Failure free survival: Time to disease recurrence or death as a first event.


Secondary Outcome Measures:
  • Rate of Local Failure for Patients Who Receive Reduced Doses of Radiation Therapy [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    The local failure rate will be estimated using cumulative incidence curves.

  • Rate of Second-look Surgery and the Proportion of Patients Who Are Tumor-free or With Microscopic Tumor Only Following Second-look Surgeries [ Time Frame: At 13 weeks ] [ Designated as safety issue: No ]
    The decision to perform second-look surgery should be based on the physical examination and imaging studies at Week 12 and should only be considered if a reasonable functional and cosmetic result is anticipated.

  • Rate of Local Failure for Patients With Clinical Group III Disease When the Radiotherapy Dose is Reduced After Second-look Surgical Resection. [ Time Frame: Up to 20 weeks ] [ Designated as safety issue: No ]
    The local failure rate will be estimated using cumulative incidence curves.


Enrollment: 390
Study Start Date: September 2004
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Regimen I (chemotherapy, radiotherapy)
Patients receive VAC chemotherapy comprising vincristine sulfate IV over 1 minute on day 1 of weeks 1-9 and dactinomycin IV over 1 minute and cyclophosphamide IV over 1 hour on day 1 of weeks 1, 4, 7, and 10; VA chemotherapy comprising vincristine sulfate IV over 1 minute on day 1 of weeks 13-21 and dactinomycin IV over 1 minute on day 1 of weeks 13, 16, 19, and 22 (dactinomycin is omitted during radiation therapy); and radiation therapy, 5 days a week, beginning on week 13 and continuing for 4-7 weeks, depending on prescribed dose. Some patients do not receive radiation therapy; some start it at week 24. (closed to accrual as of 08/13/2010)
Drug: dactinomycin
Given IV
Other Names:
  • ACT-D
  • actinomycin C1
  • AD
  • Cosmegen
  • DACT
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Radiation: radiation therapy
Undergo radiotherapy
Other Names:
  • irradiation
  • radiotherapy
  • therapy, radiation
Experimental: Regimen II (chemotherapy, radiotherapy, surgery)
Patients receive VAC chemotherapy and radiation therapy as in regimen I and VA chemotherapy comprising vincristine sulfate IV over 1 minute on day 1 of weeks 13-21, 25-33, and 37-45 and dactinomycin IV over 1 minute on day 1 of weeks 13, 16, 19, 22, 25, 28, 31, 34, 37, 40, 43, and 46 (dactinomycin is omitted during radiation therapy). Some patients do not receive radiation therapy; some start it at week 13 and some at week 24. Some patients have conventional surgery (second-look) at Week 13 (closed to accrual as of 9/23/2011).
Procedure: conventional surgery
Some patients may undergo second-look surgery
Other Name: surgery, conventional
Drug: dactinomycin
Given IV
Other Names:
  • ACT-D
  • actinomycin C1
  • AD
  • Cosmegen
  • DACT
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Radiation: radiation therapy
Undergo radiotherapy
Other Names:
  • irradiation
  • radiotherapy
  • therapy, radiation

Detailed Description:

PRIMARY OBJECTIVES:

I. Determine the failure-free survival of patients with newly diagnosed low-risk rhabdomyosarcoma treated with vincristine (V), dactinomycin (A), cyclophosphamide (C), and radiotherapy.

SECONDARY OBJECTIVES:

I. Determine local control rates in patients treated with this regimen. II. Determine the rate of second-look surgery in patients with bulk residual tumor at diagnosis (clinical group III) and the proportion of second-look surgeries that render patients treated with this regimen tumor-free or with microscopic tumor only and evaluate the pathologic significance of that residual tumor.

III. Determine the local control rates in patients with clinical group III disease treated with response-adjusted radiotherapy doses after second-look surgical resection.

OUTLINE: This is a nonrandomized, multicenter study. Patients are assigned to 1 of 2 treatment regimens according to disease stage and clinical group.

REGIMEN I (subset 1 patients) [closed to accrual as of 08/13/2010: Patients receive VAC chemotherapy comprising vincristine IV over 1 minute on day 1 of weeks 1-9 and dactinomycin IV over 1 minute and cyclophosphamide IV over 1 hour on day 1 of weeks 1, 4, 7, and 10; VA chemotherapy comprising vincristine IV over 1 minute on day 1 of weeks 13-21 and dactinomycin* IV over 1 minute on day 1 of weeks 13, 16, 19, and 22; and radiotherapy**, 5 days a week, beginning on week 13 and continuing for 4-7 weeks, depending on prescribed dose.

REGIMEN II (subset 2 patients)[closed to accrual as of 9/23/2011]: Patients receive VAC chemotherapy and radiotherapy** as in regimen I and VA chemotherapy comprising vincristine IV over 1 minute on day 1 of weeks 13-21, 25-33, and 37-45 and dactinomycin* IV over 1 minute on day 1 of weeks 13, 16, 19, 22, 25, 28, 31, 34, 37, 40, 43, and 46. Patients with clinical group III disease may undergo second-look surgery at week 13 followed by response-adjusted radiotherapy, and continued VA* chemotherapy. In both regimens, treatment continues in the absence of disease progression or unacceptable toxicity.

NOTE: *For both regimens, dactinomycin is omitted during radiotherapy.

NOTE: **Clinical Group I tumors and those with Clinical Group III uterine/cervix primary disease with negative nodes who have undergone a complete resection (i.e. hysterectomy) at Week 13 do not receive radiotherapy at Week 13

Patients are followed up every 3 months for 1 year, every 4 months for 2 years, every 6 months for 1 year, and then annually thereafter.

  Eligibility

Ages Eligible for Study:   up to 49 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed newly diagnosed embryonal rhabdomyosarcoma (RMS), botryoid or spindle cell variants of embryonal RMS, or embryonal ectomesenchymoma, meeting criteria for 1 of the following subsets:

    • Subset 1, defined by meeting 1 of the following criteria (closed to accrual as of 08/13/2010):

      • Stage 1 and clinical group I (completely resected) or II (microscopic residual disease and/or regional lymph node involvement) disease
      • Stage 1 and clinical group III (gross residual disease) disease arising in the orbit
      • Stage 2 and clinical group I or II disease
    • Subset 2, defined by meeting 1 of the following criteria (closed to accrual as of 09/23/2011):

      • Stage 1 and clinical group III disease arising in a non-orbit site
      • Stage 3 and clinical group I or II disease
  • Prior staging ipsilateral retroperitoneal lymph node dissection required for all patients age 10 and over with paratesticular tumors and patients under 10 years of age with clinically or radiographically involved lymph nodes (except when extensive lymph node involvement is identified by imaging studies)

    • If there is extensive gross node involvement only confirmatory node biopsy is recommended and the patient is classified as Clinical Group III
  • Prior regional lymph node sampling required for patients with extremity tumors
  • None of the following diagnoses:

    • Intermediate-risk embryonal RMS
    • Metastatic embryonal RMS
    • Alveolar RMS
    • Undifferentiated sarcoma
    • RMS not otherwise specified (NOS)
    • Other soft tissue sarcoma, including sarcoma NOS
  • Prior enrollment on clinical trial COG-D9902
  • Performance status - ECOG 0-2
  • Performance status - Karnofsky 50-100% (≥ 16 years old)
  • Performance status - Lansky 50-100% (< 16 years old)
  • Absolute neutrophil count at least 750/mm^3
  • Platelet count at least 75,000/mm^3 (transfusion independent)
  • Bilirubin no greater than 1.5 times upper limit of normal (ULN)*
  • Creatinine* based on age/gender as follows:

    • No greater than 0.8 mg/dL for patients age 5 and under
    • No greater than 1.0 mg/dL for patients age 6 to 9
    • No greater than 1.2 mg/dL for patients age 10 to 12
    • No greater than 1.4 mg/dL for female patients age 13 and over
    • No greater than 1.5 mg/dL for male patients age 13 to 15
    • No greater than 1.7 mg/dL for male patients age 16 and over
  • Creatinine clearance* or radioisotope glomerular filtration rate at least 70 mL/min/1.73 m^2
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No uncontrolled infection
  • No prior chemotherapy (except for patients treated on the related intermediate-risk study)
  • Prior steroids allowed
  • No prior 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: NCT00075582

  Show 163 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Principal Investigator: David Walterhouse, MD Children's Oncology Group
  More Information

No publications provided

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00075582     History of Changes
Other Study ID Numbers: ARST0331, NCI-2009-00425, COG-ARST0331, CDR0000347078, U10CA098543
Study First Received: January 9, 2004
Results First Received: December 16, 2013
Last Updated: March 6, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Rhabdomyosarcoma
Rhabdomyosarcoma, Embryonal
Myosarcoma
Neoplasms, Muscle Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Sarcoma
Dactinomycin
Cyclophosphamide
Vincristine
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Anti-Bacterial Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Myeloablative Agonists
Tubulin Modulators
Antimitotic Agents

ClinicalTrials.gov processed this record on July 24, 2014