Combination Chemotherapy in Treating Patients With Previously Untreated Rhabdomyosarcoma

Brief Title

Combination Chemotherapy in Treating Patients With Previously Untreated Rhabdomyosarcoma

Official Title

Randomized Study of Vincristine, Actinomycin-D, and Cyclophosphamide (VAC) Versus VAC Alternating With Vincristine, Topotecan and Cyclophosphamide for Patients With Intermediate Risk Rhabdomyosarcoma

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.
    

Study Phase

Phase 3

Study Type

Interventional


Primary Outcome

Long-term failure-free survival (FFS) between the two treatment groups

Secondary Outcome

 Overall survival between treatments

Condition

Adult Malignant Mesenchymoma

Intervention

dactinomycin

Study Arms / Comparison Groups

 Arm I
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.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Biological

Estimated Enrollment

702

Start Date

September 2002


Primary Completion Date

October 2007

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
      

Gender

All

Ages

N/A - 49 Years

Accepts Healthy Volunteers

No

Contacts

Carola Arndt, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT00003958

Organization ID

D9803

Secondary IDs

NCI-2012-02302

Responsible Party

Sponsor

Study Sponsor

Children's Oncology Group

Collaborators

 National Cancer Institute (NCI)

Study Sponsor

Carola Arndt, Principal Investigator, Children's Oncology Group


Verification Date

June 2013