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
N/A
21 Years
Both
Brain and Central Nervous System Tumors, Leukemia, Lymphoma, Neuroblastoma, Sarcoma, Unspecified Childhood Solid Tumor, Protocol Specific
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 Hospital | Miami, Florida 33155-4069 |
| Children's Memorial Hospital - Chicago | Chicago, Illinois 60614 |
| Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute | Boston, Massachusetts 02115 |
| St. Louis Children's Hospital | Saint Louis, Missouri 63110 |
| NYU Cancer Institute at New York University Medical Center | New York, New York 10016 |
| Children's Hospitals and Clinics of Minnesota - Minneapolis | Minneapolis, Minnesota 55404 |
| Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School | New Brunswick, New Jersey 08903 |
| Connecticut Children's Medical Center | Hartford, Connecticut 06106 |
| Hasbro Children's Hospital | Providence, Rhode Island 02903 |
| Maine Medical Center Research Institute | Scarborough, Maine 04074-7205 |
