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NCT00003958 · CITED IN SOURCE DOCUMENTS

Combination Chemotherapy in Treating Patients With Previously Untreated Rhabdomyosarcoma

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

Phase
PHASE3
Status at capture
COMPLETED
Registry last update
2013-06-17

This randomized phase III trial is comparing two different combination chemotherapy regimens to see how well each works in treating patients with previously untreated rhabdomyosarcoma or sarcoma. Drugs used in chemotherapy, such as dactinomycin, cyclophosphamide, vincristine, and topotecan, use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known which combination chemotherapy regimen is more effective in treating rhabdomyosarcoma.

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 proven disease of any of the following types: * Non metastatic alveolar rhabdomyosarcoma * Stage I, II, or III; Clinical Group I, II, or III * Stage II or III, Clinical Group III embryonal rhabdomyosarcoma * Botryoid * Spindle cell * Under 10 years, stage IV, Clinical Group IV embryonal rhabdomyosarcoma * Botryoid * Spindle cell * Undifferentiated sarcoma * Stage I, II, or III; Clinical Group I, II, or III * Ectomesenchymoma * Stage I, II, or III; Clinical Group I, II, or III, with alveolar features * Under 10 years, Stage IV, Clinical Group IV, with embryonal features * No more than 6 weeks since initial surgical procedure (e.g., biopsy) giving the definitive diagnosis * No parameningeal rhabdomyosarcoma with positive CSF cytology or multiple intracranial metastases * Bilirubin no greater than 1.5 mg/dL * Creatinine normal\* for age * Not pregnant or nursing * Fertile patients must use effective contraception * No prior chemotherapy * Prior steroids allowed * No prior radiotherapy * See Disease Characteristics
healthy Volunteers
false
maximum Age
49 Years
sex
ALL
std Ages
  1. CHILD
  2. ADULT
Treatment arms and interventions
arm Groups
  1. description
    Vincristine sulfate IV once a wk on wks 0-12, 15, 18-24, 27, 30-36, and 39. Dactinomycin IV once a wk on wks 0, 3, 6, 9, 12, 21, 24, 27, 30, 33, 36, and 39. Cyclophosphamide IV once a wk on wks 0, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, and 39. After 12 weeks of chemotherapy, depending on tumor shrinkage, pts may undergo surgery. After recovery from therapeutic conventional surgery, patients receive radiation therapy once a day, 5 days a wk, during wks 12-18. For pt receiving radiotherapy during wks 0-6, dactinomycin is omitted during wks 3 and 6 and during wks 15 and 18. For patients receiving radiotherapy during wks 12-18, dactinomycin is omitted during wks 15 and 18. Patients with adequate response at wk 24 continue chemotherapy during wks 24-39. All pts receive filgrastim (G-CSF) or sargramostim (GM-CSF) subcutaneously beginning 24 hours after completion of each course of chemotherapy and continuing 1 year, until hematopoietic recovery.
    intervention Names
    1. Biological: dactinomycin
    2. Drug: vincristine sulfate
    3. Drug: cyclophosphamide
    4. Procedure: therapeutic conventional surgery
    5. Radiation: radiation therapy
    6. Biological: filgrastim
    7. Biological: sargramostim
    8. Other: laboratory biomarker analysis
    label
    Arm I
    type
    EXPERIMENTAL
  2. description
    Patients receive treatment as in arm I, except dactinomycin is replaced with topotecan hydrochloride IV over 15-30 minutes daily for 5 days during weeks 3, 9, 21, 27, 33, and 39. All patients receive filgrastim (G-CSF) or sargramostim (GM-CSF) subcutaneously beginning 24 hours after completion of each course of chemotherapy and continuing 1 year, until hematopoietic recovery.
    intervention Names
    1. Drug: vincristine sulfate
    2. Drug: cyclophosphamide
    3. Procedure: therapeutic conventional surgery
    4. Radiation: radiation therapy
    5. Drug: topotecan hydrochloride
    6. Biological: filgrastim
    7. Biological: sargramostim
    8. Other: laboratory biomarker analysis
    label
    Arm II
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. Arm I
    description
    Given IV
    name
    dactinomycin
    other Names
    1. ACT-D
    2. actinomycin C1
    3. AD
    4. Cosmegen
    5. DACT
    type
    BIOLOGICAL
  2. 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
  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
    Undergo surgery
    name
    therapeutic conventional surgery
    type
    PROCEDURE
  5. arm Group Labels
    1. Arm I
    2. Arm II
    description
    Undergo radiotherapy
    name
    radiation therapy
    other Names
    1. irradiation
    2. radiotherapy
    3. therapy, radiation
    type
    RADIATION
  6. arm Group Labels
    1. Arm II
    description
    Given IV
    name
    topotecan hydrochloride
    other Names
    1. hycamptamine
    2. Hycamtin
    3. SKF S-104864-A
    4. TOPO
    type
    DRUG
  7. arm Group Labels
    1. Arm I
    2. Arm II
    description
    Given SC
    name
    filgrastim
    other Names
    1. G-CSF
    2. Neupogen
    type
    BIOLOGICAL
  8. 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
  9. 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
702
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. measure
    Long-term failure-free survival (FFS) between the two treatment groups
    time Frame
    Up to 5 years
secondary Outcomes
  1. measure
    Overall survival between treatments
    time Frame
    Up to 5 years
  2. measure
    Rate of second look surgery
    time Frame
    Week 12
  3. measure
    Proportion of patients rendered tumor-free or with microscopic tumor only
    time Frame
    Week 12
  4. description
    Done using standard cumulative incidence curves.
    measure
    Estimation of the rate of local failure for the patients who undergo second look surgery
    time Frame
    Week 12
Full study description
brief Summary
This randomized phase III trial is comparing two different combination chemotherapy regimens to see how well each works in treating patients with previously untreated rhabdomyosarcoma or sarcoma. Drugs used in chemotherapy, such as dactinomycin, cyclophosphamide, vincristine, and topotecan, use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known which combination chemotherapy regimen is more effective in treating rhabdomyosarcoma.
detailed Description
OBJECTIVES: I. Compare the early response rates, failure-free survival, and survival of patients with intermediate-risk rhabdomyosarcoma treated with surgery, radiotherapy, and vincristine, dactinomycin, and cyclophosphamide (VAC) vs VAC alternating with vincristine, topotecan, and cyclophosphamide. II. Compare the acute and late effects of these two treatment regimens in these patients. III. Determine the rate of second-look surgery in selected patients with bulk residual tumor at diagnosis (i.e., Clinical Group III) and the proportion of these that render the patient tumor free or with microscopic tumor only. IV. Determine the rate of local failure in selected patients with bulk residual tumors at diagnosis (i.e., Clinical Group III) who, after second-look resection, have response-adjusted radiotherapy dose reduction. V. Determine if preoperative radiotherapy followed by second-look surgery is feasible for selected patients with bulk residual disease (i.e., Clinical Group III) who respond poorly to induction chemotherapy. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to disease (embryonal histology, stage II or III, Clinical Group III vs embryonal histology, Clinical Group IV, less than 10 years of age vs alveolar or undifferentiated sarcoma histology, stage I, Clinical Group I vs alveolar or undifferentiated sarcoma histology, stage II or III, Clinical Group II or III). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive vincristine IV over 5-10 minutes once a week on weeks 0-12, 15, 18-24, 27, 30-36, and 39. Dactinomycin IV is administered over 15-20 minutes once a week on weeks 0, 3, 6, 9, 12, 21, 24, 27, 30, 33, 36, and 39. Cyclophosphamide IV is administered over 30-60 minutes once a week on weeks 0, 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, and 39. After the initial 12 weeks of chemotherapy, depending on tumor shrinkage, patients may undergo surgery. After recovery from surgery, patients receive radiotherapy once a day, 5 days a week, during weeks 12-18. For patients receiving radiotherapy during weeks 0-6, dactinomycin is omitted during weeks 3 and 6 and administered during weeks 15 and 18. For patients receiving radiotherapy during weeks 12-18, dactinomycin is omitted during weeks 15 and 18. Patients showing an adequate response at week 24 continue chemotherapy during weeks 24-39. Patients with Clinical Group III tumors of a parameningeal site with documented evidence of intracranial extension receive radiotherapy within the first 2 weeks of the initiation of the first course of chemotherapy (day 0). Patients with Clinical Group II parameningeal tumors and Clinical Group III parameningeal tumors with base of skull erosion and/or cranial nerve palsy without evidence of intracranial extension receive radiotherapy on week 12 (day 84) or immediately thereafter. Patients with Clinical Group IV parameningeal tumors with distant metastases receive radiotherapy to the primary site on week 12 (day 84). Patients with distant metastases confined to one site may receive radiotherapy to the metastatic site concurrently with therapy to the primary site if it began within 2 weeks of the initiation of chemotherapy (day 0). Arm II: Patients receive treatment as in arm I, except dactinomycin is replaced with topotecan IV over 15-30 minutes daily for 5 days during weeks 3, 9, 21, 27, 33, and 39. All patients receive filgrastim (G-CSF) or sargramostim (GM-CSF) subcutaneously beginning 24 hours after completion of each course of chemotherapy and continuing 1 year, until hematopoietic recovery. Patients are followed every 1-2 months for 1 year, every 3 months for 1 year, every 6 months for 1 year, and then annually thereafter.
Source references
references
  1. citation
    de Traux de Wardin H, Dermawan JK, Vanoli F, Jiang SC, Singer S, Chi P, Tap W, Wexler LH, Antonescu CR. NF1-Driven Rhabdomyosarcoma Phenotypes: A Comparative Clinical and Molecular Study of NF1-Mutant Rhabdomyosarcoma and NF1-Associated Malignant Triton Tumor. JCO Precis Oncol. 2024 Apr;8:e2300597. doi: 10.1200/PO.23.00597.
    pmid
    38603649
    type
    DERIVED
Source notices and limitations
    Discovery and provenance
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      1. context exact
        of about 75% and a local control rate of 87%.[<a href="#cit/section_1.58">58</a>] Two intermediate-risk COG rhabdomyosarcoma studies (<a href="/clinicaltrials/NCT00003958">D9803</a> and <a href="/clinicaltrials/NCT00354835">ARST0531 [NCT00354835]</a>) were pooled to assess the benefit of delayed primary excision. In the D9803 st
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      2. context exact
        Sarcoma Committee of the COG that examined 434 cases of intermediate-risk rhabdomyosarcoma treated on a single intermediate protocol (<a href="/clinicaltrials/NCT00003958">D9803</a>) confirmed these observations.[<a href="#cit/section_1.70">70</a>] Analysis of 38 patients enrolled in the COG <a href="/clinicaltrials/NCT00003955"
        end
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      3. context exact
        ow. These patients were enrolled in one of four COG rhabdomyosarcoma clinical trials (<a href="/clinicaltrials/NCT00003955">D9802</a>, <a href="/clinicaltrials/NCT00003958">D9803</a>, <a href="/clinicaltrials/NCT00354744">ARST0431</a>, and <a href="/clinicaltrials/NCT01055314">ARST08P1</a>) between 1997 and 2013.[<a href="#cit/se
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      4. context exact
        ion was evaluated by the Soft Tissue Sarcoma Committee of the COG (COG-STS) in the <a href="/clinicaltrials/NCT00002995">D9602</a> and <a href="/clinicaltrials/NCT00003958">D9803</a> studies.[<a href="#cit/section_6.8">8</a>] Delayed primary excision at week 12 after induction chemotherapy was completed in 45% to 54% of patient
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        exact text
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      5. context exact
        abindex="-1"> A retrospective analysis compared patients with clinical Group III rhabdomyosarcoma treated on consecutive COG protocols <a href="/clinicaltrials/NCT00003958">D9803</a> (encouraged delayed primary excision) and <a href="/clinicaltrials/NCT00354835">ARST0531 (NCT00354835)</a> (discouraged delayed primary excision).[<
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        251118
        exact text
        NCT00003958
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      6. context exact
        2" tabindex="-1">Patients with lung metastases who were enrolled in four COG studies (<a href="/clinicaltrials/NCT00003955">D9802</a>, <a href="/clinicaltrials/NCT00003958">D9803</a>, <a href="/clinicaltrials/NCT01055314">ARST08P1</a>, and <a href="/clinicaltrials/NCT00354744">ARST0431</a>) were retrospectively analyzed. All four
        end
        269710
        exact text
        NCT00003958
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      7. context exact
        se results highlight the potential importance of whole-lung irradiation.</p></li></ul></div> <p id="_765" tabindex="-1">In the <a href="/clinicaltrials/NCT00003958">D9803</a> study of patients with intermediate-risk rhabdomyosarcoma, local control was 90% in 41 patients with Groups I and II alveolar rhabdomyosarcoma but l
        end
        271159
        exact text
        NCT00003958
        start
        271148
      8. context exact
        alveolar histology that were treated with more intensive intermediate-risk protocols [<a href="/clinicaltrials/NCT00003955">D9802</a>, <a href="/clinicaltrials/NCT00003958">D9803</a> and <a href="/clinicaltrials/NCT00354835">ARST0531</a>]), had 5-year EFS and OS rates of 88.5% (95% CI, 75.6%&#8211;100.0%) and 95.8% (95% CI, 87.7%
        end
        289071
        exact text
        NCT00003958
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      9. context exact
        RS-IV study with cranial nerve palsy and/or cranial base erosion versus later initiation of RT (week 12) for Group III patients in the <a href="/clinicaltrials/NCT00003958">D9803</a> study who had similar evidence of meningeal involvement. This suggested that early RT for this group of patients is not necessary.[<a href="#cit/sec
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      10. context exact
        at baseline, 6 of whom experienced a local recurrence.</li><li>This recurrence rate is similar to the rate reported in the IRS-IV and <a href="/clinicaltrials/NCT00003958">D9803</a> trials for patients with high-risk parameningeal rhabdomyosarcoma.[<a href="#cit/section_6.75">75</a>]</li></ul></div> </li><li>A study included 1
        end
        296674
        exact text
        NCT00003958
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        296663
      11. context exact
        n has been studied in patients with extremity tumors enrolled in the COG intermediate-risk rhabdomyosarcoma trials. Two COG studies (<a href="/clinicaltrials/NCT00003958">D9803</a> and <a href="/clinicaltrials/NCT00354835">ARST0531 [NCT00354835]</a>) were pooled to assess the benefit of delayed primary excision. In the D9803 st
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        302717
        exact text
        NCT00003958
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      12. context exact
        olled in one of four COG studies (<a href="/clinicaltrials/NCT00002995">D9602</a>, <a href="/clinicaltrials/NCT00075582">ARST0331</a>, <a href="/clinicaltrials/NCT00003958">D9803</a>, or <a href="/clinicaltrials/NCT00354835">ARST0531 [NCT00354835]</a>). Surgical resection of the primary tumor before chemotherapy and RT was encour
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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