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Anti-Angiogenic Chemotherapy: A Phase II Trial of the Oral 5-Drug Regimen (Thalidomide, Celecoxib, Fenofibrate, Etoposide and Cyclophosphamide) in Patients With Relapsed or Progressive Cancer


Phase 2
N/A
21 Years
Open (Enrolling)
Both
Brain and Central Nervous System Tumors, Leukemia, Lymphoma, Neuroblastoma, Sarcoma, Unspecified Childhood Solid Tumor, Protocol Specific

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Trial Information

Anti-Angiogenic Chemotherapy: A Phase II Trial of the Oral 5-Drug Regimen (Thalidomide, Celecoxib, Fenofibrate, Etoposide and Cyclophosphamide) in Patients With Relapsed or Progressive Cancer


OBJECTIVES:

Primary

- Evaluate the activity of etoposide, cyclophosphamide, thalidomide, celecoxib, and
fenofibrate, in terms of prolonging the time to disease progression, in young patients
with relapsed or progressive cancer.

Secondary

- Determine, preliminarily, the biologic activity of this regimen, in terms of tumor
response and overall survival, in these patients.

- Determine the toxicity of this regimen in these patients.

- Evaluate different radiographic techniques as markers of tumor response in these
patients.

- Evaluate the predictive ability of in vitro correlative studies as markers of tumor
response.

OUTLINE: This is a multicenter study. Patients are stratified according to disease type
(leukemia/lymphoma vs bone tumors [Ewing's sarcoma, osteosarcoma] vs neuroblastoma vs
high-grade glial tumors vs low-grade glial tumors vs ependymomas vs
medulloblastoma/primitive neuroectodermal tumor [PNET] vs miscellaneous tumors).

Patients receive oral etoposide once daily on days 1-21 and 43-63 (weeks 1-3 and 7-9) and
oral cyclophosphamide once daily on days 22-42 (weeks 4-6). Patients also receive oral
thalidomide once daily, oral celecoxib twice daily, and oral fenofibrate once daily in weeks
1-9. Treatment repeats approximately every 9 weeks for at least 3 courses in the absence of
disease progression or unacceptable toxicity. Patients receive alternating etoposide and
cyclophosphamide pulses (i.e., etoposide-cyclophosphamide-etoposide during courses 1 and 3
and cyclophosphamide-etoposide-cyclophosphamide during course 2).

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 180 patients will be accrued for this study.

Inclusion 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

Type of Study:

Interventional

Study Design:

Primary Purpose: Treatment

Outcome Measure:

Time to disease progression

Safety Issue:

No

Principal Investigator

Mark W. Kieran, MD, PhD

Investigator Role:

Study Chair

Investigator Affiliation:

Dana-Farber Cancer Institute

Authority:

United States: Federal Government

Study ID:

CDR0000487628

NCT ID:

NCT00357500

Start Date:

January 2005

Completion Date:

Related Keywords:

  • Brain and Central Nervous System Tumors
  • Leukemia
  • Lymphoma
  • Neuroblastoma
  • Sarcoma
  • Unspecified Childhood Solid Tumor, Protocol Specific
  • accelerated phase chronic myelogenous leukemia
  • blastic phase chronic myelogenous leukemia
  • chronic phase chronic myelogenous leukemia
  • meningeal chronic myelogenous leukemia
  • recurrent childhood acute lymphoblastic leukemia
  • recurrent childhood acute myeloid leukemia
  • recurrent childhood medulloblastoma
  • recurrent childhood supratentorial primitive neuroectodermal tumor
  • recurrent Ewing sarcoma/peripheral primitive neuroectodermal tumor
  • recurrent/refractory childhood Hodgkin lymphoma
  • relapsing chronic myelogenous leukemia
  • secondary acute myeloid leukemia
  • anaplastic large cell lymphoma
  • angioimmunoblastic T-cell lymphoma
  • recurrent osteosarcoma
  • untreated childhood medulloblastoma
  • recurrent neuroblastoma
  • childhood oligodendroglioma
  • childhood chronic myelogenous leukemia
  • recurrent childhood brain stem glioma
  • recurrent childhood visual pathway and hypothalamic glioma
  • untreated childhood brain stem glioma
  • untreated childhood visual pathway and hypothalamic glioma
  • childhood infratentorial ependymoma
  • childhood supratentorial ependymoma
  • newly diagnosed childhood ependymoma
  • recurrent childhood ependymoma
  • unspecified childhood solid tumor, protocol specific
  • childhood grade III lymphomatoid granulomatosis
  • childhood nasal type extranodal NK/T-cell lymphoma
  • recurrent childhood grade III lymphomatoid granulomatosis
  • recurrent childhood large cell lymphoma
  • childhood diffuse large cell lymphoma
  • childhood immunoblastic large cell lymphoma
  • recurrent childhood lymphoblastic lymphoma
  • Burkitt lymphoma
  • recurrent childhood small noncleaved cell lymphoma
  • intraocular lymphoma
  • primary central nervous system non-Hodgkin lymphoma
  • childhood high-grade cerebral astrocytoma
  • childhood low-grade cerebral astrocytoma
  • recurrent childhood cerebral astrocytoma
  • recurrent cutaneous T-cell non-Hodgkin lymphoma
  • recurrent mycosis fungoides/Sezary syndrome
  • recurrent childhood cerebellar astrocytoma
  • recurrent childhood brain tumor
  • untreated childhood acute lymphoblastic leukemia
  • untreated childhood acute myeloid leukemia and other myeloid malignancies
  • untreated childhood cerebellar astrocytoma
  • untreated childhood supratentorial primitive neuroectodermal tumor
  • disseminated neuroblastoma
  • metastatic Ewing sarcoma/peripheral primitive neuroectodermal tumor
  • metastatic osteosarcoma
  • stage IV chronic lymphocytic leukemia
  • stage IV childhood Hodgkin lymphoma
  • stage IV childhood large cell lymphoma
  • stage IV childhood lymphoblastic lymphoma
  • stage IV childhood small noncleaved cell lymphoma
  • stage IV cutaneous T-cell non-Hodgkin lymphoma
  • stage IV mycosis fungoides/Sezary syndrome
  • T-cell large granular lymphocyte leukemia
  • Leukemia
  • Lymphoma
  • Nervous System Neoplasms
  • Neuroblastoma
  • Central Nervous System Neoplasms
  • Neuroectodermal Tumors, Primitive
  • Neuroectodermal Tumors, Primitive, Peripheral
  • Sarcoma

Name

Location

Miami Children's HospitalMiami, Florida  33155-4069
Children's Memorial Hospital - ChicagoChicago, Illinois  60614
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer InstituteBoston, Massachusetts  02115
St. Louis Children's HospitalSaint Louis, Missouri  63110
NYU Cancer Institute at New York University Medical CenterNew York, New York  10016
Children's Hospitals and Clinics of Minnesota - MinneapolisMinneapolis, Minnesota  55404
Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical SchoolNew Brunswick, New Jersey  08903
Connecticut Children's Medical CenterHartford, Connecticut  06106
Hasbro Children's HospitalProvidence, Rhode Island  02903
Maine Medical Center Research InstituteScarborough, Maine  04074-7205