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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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 Multiage

Brief Summary: 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

Detailed Summary:

OBJECTIVES:

I. Compare response rate in children with relapsed or progressive rhabdomyosarcoma, undifferentiated sarcoma, or ectomesenchymoma treated with 2 different schedules of irinotecan and vincristine in an upfront phase II window.

II. Determine the progression-free and overall survival of patients treated with multiagent chemotherapy.

III. Determine the toxic effects of tirapazamine, doxorubicin, and cyclophosphamide in these patients.

IV. Determine the toxic effects of irinotecan and vincristine in these patients.

V. Determine whether conversion of irinotecan to its active metabolite SN-38 predicts tumor response in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to risk status and window therapy eligibility (unfavorable risk and eligible vs unfavorable risk and ineligible vs favorable risk).

UNFAVORABLE-RISK PATIENTS ELIGIBLE FOR WINDOW THERAPY: Patients are stratified according to prior topotecan (yes vs no). These patients are randomized to 1 of 2 treatment arms.

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.

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.

  • Response at week 6 of investigational window therapy (unfavorable risk patients) [ Time Frame: At week 6 ]
  • 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 ]


    • Original Primary Outcome:

    Current Secondary Outcome:

    • 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 ]
    • Blood metabolite SN-38 levels (unfavorable risk patients) [ Time Frame: Up to 6 years ]
    • Progression-free survival [ Time Frame: Up to 6 years ]
    • Survival [ Time Frame: Up to 6 years ]


    Original Secondary Outcome:

    Information By: National Cancer Institute (NCI)

    Dates:
    Date Received: October 11, 2001
    Date Started: November 2001
    Date Completion:
    Last Updated: January 16, 2013
    Last Verified: January 2013