Etoposide, Cyclophosphamide, Thalidomide, Celecoxib, and Fenofibrate in Relapsed or Progressive Cancer
Condition: Central Nervous System Tumor, Pediatric; Leukemia; Lymphoma; Neuroblastoma; Sarcoma; Unspecified Childhood Solid Tumor, Protocol Specific
MeSH terms: Neuroblastoma; Nervous System Neoplasms; Central Nervous System Neoplasms
Intervention: celecoxib; cyclophosphamide; etoposide; fenofibrate; thalidomide
Intervention MeSH terms: Thalidomide; Celecoxib; Cyclophosphamide; Etoposide; Fenofibrate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 101.0
Sex: All
Maximum age: 21 Years
Healthy volunteers: No
Keywords: Metronomic; antiangiogenic

Summary:

      RATIONALE: Drugs used in chemotherapy, such as etoposide and cyclophosphamide, work in
      different ways to stop the growth of cancer cells, either by killing the cells or by stopping
      them from dividing. Thalidomide, celecoxib, and fenofibrate may stop the growth of cancer
      cells by blocking blood flow to the cancer. Celecoxib also may stop the growth of cancer
      cells by blocking some of the enzymes needed for cell growth. Giving combination chemotherapy
      together with thalidomide, celecoxib, and fenofibrate may kill more cancer cells.

      PURPOSE: This phase II trial is studying how well giving etoposide and cyclophosphamide
      together with thalidomide, celecoxib, and fenofibrate works in treating young patients with
      relapsed or progressive cancer.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Histologically confirmed cancer (at diagnosis or relapse), including any of the
             following:

               -  Leukemia and/or lymphoma (closed to accrual)

               -  Bone tumor (e.g., Ewing's sarcoma or osteosarcoma) (closed to accrual)

               -  Neuroblastoma (closed to accrual)

               -  High-grade glial tumor

               -  Low-grade glial tumor

               -  Ependymoma

               -  Medulloblastoma and/or primitive neuroectodermal tumor (PNET)

               -  Miscellaneous tumor (closed to accrual)

               -  Brain stem glioma, defined as intrinsic tumors of the pons causing diffuse
                  enlargement

                    -  Brain stem glioma that progressed after radiotherapy does not require
                       histological confirmation

                    -  Duration of symptoms at the time of diagnosis must be < 3 months

                         -  Symptoms should consist of cranial nerve deficits, ataxia, and/or long
                            tract signs

          -  Relapsed or progressive poor prognosis disease for which no available curative therapy
             exists

        PATIENT CHARACTERISTICS:

          -  Karnofsky performance status 50-100% OR Lansky play scale 50-100% (for infants)

          -  Life expectancy > 2 months

          -  Platelet count > 75,000/mm^3 (transfusion independent)

          -  Absolute neutrophil count > 1,000/mm^3 (in patients without bone marrow disease)

          -  Hemoglobin ≥ 9.0 g/dL

          -  Creatinine < 1.5 mg/dL OR creatinine clearance or glomerular filtration rate ≥ 70
             mL/min

          -  Bilirubin ≤ 1.5 mg/dL

          -  SGPT ≤ 3 times normal

          -  SGOT ≤ 3 times normal (4 times normal for patients on ranitidine hydrochloride)

          -  Alkaline phosphatase ≤ 3 times normal

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective double-method contraception during and for 2
             months after completion of study treatment

          -  Must be willing to participate in the Celgene STEPS® program

          -  Recent thromboembolic disease (e.g., deep vein thrombosis or pulmonary embolism)
             allowed if patient is clinically stable and the thromboembolic event occurred > 3
             weeks prior to study entry

          -  No active infection

          -  No active uncontrolled cardiac, hepatic, renal, or psychiatric disease ≥ grade 3

          -  No known allergies to sulfonamides

          -  No concurrent illness that would obscure toxicity or dangerously alter drug metabolism

          -  No other serious medical illness

        PRIOR CONCURRENT THERAPY:

          -  See Disease Characteristics

          -  Recovered from prior therapy

          -  Prior chemotherapy and/or radiotherapy allowed

          -  Prior celecoxib allowed

          -  Prior standard-dose IV etoposide and cyclophosphamide administered in 3-week courses
             allowed

          -  No prior oral therapy with etoposide, thalidomide, cyclophosphamide, or fenofibrate
             for > 2 months in duration

          -  No other concurrent investigational agents

          -  No other concurrent nonsteroidal anti-inflammatory drugs

          -  Concurrent steroids and/or antiseizure medications allowed