Vinblastine, Celecoxib, and Combination Chemotherapy in Treating Patients With Newly-Diagnosed Metastatic Ewing's Sarcoma Family of Tumors
Condition: Sarcoma
MeSH terms: Sarcoma; Sarcoma, Ewing
Intervention: celecoxib; cyclophosphamide; doxorubicin hydrochloride; etoposide; ifosfamide; vinblastine sulfate; vincristine sulfate; conventional surgery; radiation therapy; MESNA; Filgrastim
Intervention description: Given orally, Celecoxib 250 mg/m2 PO BID (500mg/m2/day) from Day 1 of Cycle 1 through Day 21 of Cycle 14. The dose should be rounded off to the nearest 100 mg. If PK studies are being done, Celecoxib should be given 24 hours prior to the other drugs for Cycle 1 only. [Celecoxib may be interrupted for up to 7 days around the time of surgical procedures.] .; Given IV, 1200 mg/m2 IV infusion over 1 hour with MESNA uroprotection, on Day 1. For children < 1 year treat with 50% doses calculated on a m2 basis. If tolerated (no delay in administration of the next cycle due to delayed count recovery or delayed resolution of other toxicities and no serious toxicities), consider increasing to 75% and then to 100% of the calculated full dose.; Given IV, Doxorubicin 75 mg/ m2 /course continuous IV infusion over 48 hours, beginning Day 1. Note: The total doxorubicin dose per cycle is 75 mg/ m2, which will be given as 37.5 mg/m2/day x 2 days. Doxorubicin may be given as a continuous infusion or brief infusion.; Given IV, Vincristine 2 mg/m2 IV push, on Day 1. Maximum dose 2 mg. For children < 1 year treat with 50% doses calculated on a m2 basis. If tolerated (no delay in administration of the next cycle due to delayed count recovery or delayed resolution of other toxicities and no serious toxicities), consider increasing to 75% and then to 100% of the calculated full dose.; Given IV,Ifosfamide 1800 mg/m2 /day IV infusion over 1 hour, Days 1-5 of each cycle. (9,000 mg/m2 max total dose per cycle). Prehydrate for 6 hours, 1,000 ml/m2 total volume (165 ml/m2/hour for 6 hours). For children < 1 year treat with 50% doses calculated on a m2 basis. If tolerated (no delay in administration of the next cycle due to delayed count recovery or delayed resolution of other toxicities and no serious toxicities), consider increasing to 75% and then to 100% of the calculated full dose.; Given IV, Vinblastine 1 mg/m2/d IV push three times per week beginning Day 1 of Cycle 1 and continuing through Day 21 of Cycle 14. In weeks during which vincristine is given, hold one dose of vinblastine and administer only 2 doses of vinblastine during that week. If vinblastine is due the same day as vincristine, hold that dose of vinblastine. [Vinblastine may be interrupted for up to 7 days around the time of surgical procedures.]; Given IV, Vincristine 2 mg/m2 IV push, on Day 1. Maximum dose 2 mg. For children < 1 year treat with 50% doses calculated on a m2 basis. If tolerated (no delay in administration of the next cycle due to delayed count recovery or delayed resolution of other toxicities and no serious toxicities), consider increasing to 75% and then to 100% of the calculated full dose.; Patients who respond to induction chemotherapy undergo surgery on week 13. Patients who have inadequate margins after surgery undergo radiotherapy beginning on week 15. (see Detailed Description for frequency of administration and groups evaluated); Patients with unresectable lesions undergo radiotherapy 5 days a week for approximately 6 weeks beginning on week 13. (see Detailed Description for frequency of administration and groups evaluated); The total daily MESNA dose is equal to at least 60% of the daily cyclophosphamide or ifosfamide dose, or by continuous infusion of the 60% dose. MESNA continuous infusion should be started at the same time as the cyclophosphamide/ifosfamide and be completed no sooner than 8 hours after the end of the cyclophosphamide or ifosfamide infusion. The oral dose of MESNA is 2x the IV dose. Patients able to tolerate oral MESNA may receive the final dose by mouth at 40% of the oxazaphosphorine (cyclophosphamide or ifosfamide) dose. The dose should be given two hours earlier than the IV dose would be given. Additionally, if the patient vomits within two hours after the oral dose, the dose should be repeated or IV MESNA given.; G-CSF (Filgrastim) 5 micrograms/kg/day subcutaneously beginning 24 to 48 hours after the last dose of chemotherapy, and continuing until the absolute neutrophil count is 2,000/µL or greater after nadir.
Intervention MeSH terms: Celecoxib; Cyclophosphamide; Ifosfamide; Doxorubicin; Liposomal doxorubicin; Etoposide; Vincristine; Vinblastine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 38.0
Sex: All
Maximum age: 50 Years
Healthy volunteers: No
Keywords: metastatic Ewing sarcoma/peripheral primitive neuroectodermal tumor

Summary:

      RATIONALE: Drugs used in chemotherapy, such as vinblastine, work in different ways to stop
      tumor cells from dividing so they stop growing or die. Celecoxib may stop the growth of
      Ewing's sarcoma by stopping blood flow to the tumor. Combining more than one chemotherapy
      drug with celecoxib may kill more tumor cells.

      PURPOSE: Phase II trial to study the effectiveness of combining low-dose vinblastine and
      celecoxib with standard regimens of combination chemotherapy in treating patients who have
      newly-diagnosed metastatic Ewing's sarcoma family of tumors.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Newly diagnosed Ewing's sarcoma family of tumors of the bone or soft tissues

               -  Paraspinal tumors of extra-dural origin and Askin's tumor of the chest wall are
                  eligible

          -  Metastatic disease, defined by the following criteria:

               -  Lesions are discontinuous from the primary tumor, are not regional lymph nodes,
                  and do not share a body cavity with the primary tumor

               -  A single pulmonary or pleural nodule greater than 1 cm OR multiple nodules
                  greater than 0.5 cm are considered evidence of pulmonary or pleural metastases
                  (unless there is another clear medical explanation for these lesions)

               -  Contralateral pleural effusions are considered metastatic disease

          -  No CNS involvement

        PATIENT CHARACTERISTICS:

        Age

          -  50 and under (at diagnosis)

        Performance status

          -  Lansky 50-100% (under 17 years of age)

          -  Karnofsky 50-100% (age 17 and over)

               -  Patients whose performance status is affected by a pathological fracture are
                  allowed provided they are able to undergo treatment

        Life expectancy

          -  Not specified

        Hematopoietic

          -  Not specified

        Hepatic

          -  Bilirubin no greater than 1.5 times upper limit of normal (ULN)

          -  AST or ALT less than 5 times ULN

        Renal

          -  Creatinine adjusted according to age as follows*:

               -  No greater than 0.4 mg/dL (≤ 5 months)

               -  No greater than 0.5 mg/dL (6 months -11 months)

               -  No greater than 0.6 mg/dL (1 year-23 months)

               -  No greater than 0.8 mg/dL (2 years-5 years)

               -  No greater than 1.0 mg/dL (6 years-9 years)

               -  No greater than 1.2 mg/dL (10 years-12 years)

               -  No greater than 1.4 mg/dL (13 years and over [female])

               -  No greater than 1.5 mg/dL (13 years to 15 years [male])

               -  No greater than 1.7 mg/dL (16 years and over [male]) OR

          -  Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min*
             NOTE: *Unless these values are related to renal insufficiency secondary to tumor
             involvement that is expected to improve once the tumor mass is smaller (e.g., pelvic
             mass causing obstructive hydronephrosis)

        Cardiovascular

          -  Shortening fraction at least 27% by echocardiogram OR

          -  Ejection fraction at least 50% by MUGA

        Other

          -  Not pregnant or nursing

          -  Fertile patients must use effective contraception

          -  Body surface area at least 0.4 m^2

          -  No allergy to sulfa

          -  No aspirin hypersensitivity

          -  No asthma triad (asthma with nasal polyps, and urticaria)

          -  No other prior cancer, including nonmelanoma skin cancer

        PRIOR CONCURRENT THERAPY:

        Biologic therapy

          -  No prior bone marrow or stem cell transplantation

        Chemotherapy

          -  No prior chemotherapy

        Endocrine therapy

          -  Not specified

        Radiotherapy

          -  No prior radiotherapy

        Surgery

          -  Not specified

        Other

          -  No other concurrent nonsteroidal anti-inflammatory medications, including salicylates

          -  No concurrent dexrazoxane unless approved by the study investigator