High-Dose Combination Chemotherapy and Radiation Therapy in Treating Patients With Newly Diagnosed Metastatic Rhabdomyosarcoma or Ectomesenchymoma
Condition: Sarcoma
MeSH terms: Sarcoma; Rhabdomyosarcoma
Intervention: dactinomycin; cyclophosphamide; doxorubicin hydrochloride; etoposide; ifosfamide; irinotecan hydrochloride; vincristine sulfate; conventional surgery; radiation therapy; filgrastim
Intervention description: Age based dosage: ≥ 1 year 0.045 mg/kg IV x 1(maximum dose 2.5 mg), < 1 year 0.025 mg/kg.
Day 1 of Weeks 35, 38, 41 and 44.
Given IV; Age based dosage: ≥ 3 years 1200 mg/m2, <3 years 40 mg/kg.
Day 1 of weeks 7, 11, 15, 28, 32, 35, 38, 41 and 44.
Given IV; Age based dosage: ≥ 1 year: 37.5mg/m²/day, < 1 year: treat with 50% doses calculated on a m2 basis. Total dose 75 mg/m².
Days 1 and 2 of weeks 7, 11, 15, 28 and 32.
Given IV; Age based dosage: ≥ 1 year: 100 mg/m²/day, < 1 year: treat with 50% doses calculated on a m2 basis.
Days 1-5 of weeks 9, 13, 17, 26 and 30.
Given IV; Age based dosage: ≥ 1 year: 1800 mg/m²/day, < 1 year: treat with 50% doses calculated on a m2 basis.
Days 1-5 of weeks 9, 13, 17, 26 and 30.
Given IV; Dosage 50 mg/m2-max dose 100 mg/day.
Days 1-5 of weeks 1, 4, 20, 23, 47 and 50.
Given IV; Age based dosage: ≥ 3 years 1.5 mg/m2 (max dose 2 mg), ≥ 1 year and < 3 years 0.05 mg/kg (max dose 2 mg), < 1 year 0.025 mg/kg.
Days 1-5 of weeks 1, 2, 3, 4, 5, 7, 8, 11, 12, 15, 16, 20, 21, 22, 23, 24, 28, 29, 32, 33, 35, 38, 41, 42, 43, 44, 47, 48, 50, and 51.
Given IV; Resection of the primary tumor with a surrounding "envelope" of normal tissue; Radiotherapy beginning at Week 20 to the primary tumor and to the metastatic sites excepting those with parameningeal tumors with intracranial extension (direct extension into the brain) and those requiring emergency radiotherapy; 5 micrograms/kg/day (max 300 micrograms) beginning 24-36 hours after the last dose of chemotherapy. Continue at least 7 days, or until the ANC ≥750/μL whichever comes last.
Given subcutaneously.
Intervention MeSH terms: Dactinomycin; Cyclophosphamide; Ifosfamide; Isophosphamide mustard; Doxorubicin; Liposomal doxorubicin; Irinotecan; Etoposide; Vincristine; Camptothecin; Lenograstim
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 109.0
Sex: All
Maximum age: 49 Years
Healthy volunteers: No
Keywords: adult rhabdomyosarcoma; previously untreated childhood rhabdomyosarcoma; adult malignant mesenchymoma; childhood malignant mesenchymoma; metastatic childhood soft tissue sarcoma; stage IV adult soft tissue sarcoma

Summary:

      RATIONALE: Drugs used in chemotherapy, such as vincristine, irinotecan, ifosfamide,
      etoposide, doxorubicin, cyclophosphamide, and dactinomycin, 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 high-dose combination
      chemotherapy together with radiation therapy may kill more tumor cells.

      PURPOSE: This phase III trial is studying how well giving high-dose combination chemotherapy
      together with radiation therapy works in treating patients with newly diagnosed metastatic
      rhabdomyosarcoma or ectomesenchymoma.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Histologically confirmed high-risk rhabdomyosarcoma or ectomesenchymoma

               -  Prior enrollment on COG-D9902 to confirm local histological diagnosis required

                    -  Tissue must be submitted for pathologic review within 2 days of patient
                       registration on COG-D9902

               -  Newly diagnosed disease

               -  Metastatic disease (stage IV, clinical group IV)

          -  Has undergone initial surgical procedure (including biopsy) that provided the
             definitive diagnosis within the past 42 days

          -  Parameningeal and paraspinal tumors allowed

               -  Patients with parameningeal (without intracranial extension [ICE]) and paraspinal
                  tumors should begin study chemotherapy at week 1 and radiotherapy at week 20

          -  Patients with evidence of ICE, as defined by contrast MRI showing that primary tumor
             touches, displaces, invades, distorts, or otherwise causes a signal abnormality of the
             dura in contiguity to the primary site in brain or spinal cord, are eligible

               -  ICE is presumed to exist if the cerebrospinal fluid cytopathology is positive for
                  tumor at diagnosis

          -  Patients requiring emergency radiotherapy are eligible

               -  Patients requiring emergency radiotherapy (for intracranial extension or spinal
                  cord impingement) should begin study chemotherapy at week 1 (irinotecan
                  hydrochloride and vincristine) concurrently with radiation therapy

        PATIENT CHARACTERISTICS:

          -  ECOG or Zubrod performance status (PS) 0-2 (Lansky PS 50-100% for patients < 10 years
             of age and Karnofsky PS 50-100% for patients ≥ 10 years of age)

          -  Absolute neutrophil count ≥ 750/mm³*

          -  Platelet count ≥ 75,000/mm³*

          -  Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min (≥ 40
             mL/min for infants < 1 year of age)

          -  Patients with urinary tract obstruction by tumor must meet the renal function criteria
             listed above AND must have unimpeded urinary flow established via decompression of the
             obstructed portion of the urinary tract

          -  SGPT < 2.5 times normal

          -  Bilirubin < 1.5 mg/dL

          -  Shortening fraction ≥ 27% by echocardiogram OR ejection fraction ≥ 50% by MUGA

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception during study and for ≥ 1 month after
             study completion

          -  No evidence of uncontrolled infection

          -  Able to undergo radiotherapy NOTE: *Abnormal blood counts allowed if there is bone
             marrow biopsy or aspirate proven bone marrow involvement by rhabdomyosarcoma

        PRIOR CONCURRENT THERAPY:

          -  No prior chemotherapy except steroids

          -  No prior radiotherapy

          -  No concurrent aprepitant during ifosfamide or doxorubicin hydrochloride chemotherapy

          -  No concurrent dexrazoxane

          -  No concurrent sargramostim (GM-CSF) or pegfilgrastim