Etoposide, Cyclophosphamide, Thalidomide, Celecoxib, and Fenofibrate in Treating Young Patients With Relapsed or Progressive Cancer - Full Text View

Sponsor:	Dana-Farber Cancer Institute
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00357500

Purpose

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.

Condition	Intervention	Phase
Brain and Central Nervous System Tumors Leukemia Lymphoma Neuroblastoma Sarcoma Unspecified Childhood Solid Tumor, Protocol Specific	Drug: celecoxib Drug: cyclophosphamide Drug: etoposide Drug: fenofibrate Drug: thalidomide	Phase II

Study Type:	Interventional
Study Design:	Primary Purpose: Treatment
Official Title:	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

Resource links provided by NLM:

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Time to disease progression [ Designated as safety issue: No ]

Secondary Outcome Measures:

Tumor response [ Designated as safety issue: No ]
Overall survival [ Designated as safety issue: No ]
Progression-free survival [ Designated as safety issue: No ]
Toxicity [ Designated as safety issue: Yes ]
Different radiographic techniques as markers of response [ Designated as safety issue: No ]
Biological markers as markers of response/angiogenesis [ Designated as safety issue: No ]

Estimated Enrollment:	180
Study Start Date:	January 2005
Estimated Primary Completion Date:	July 2009 (Final data collection date for primary outcome measure)

Detailed Description:

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.

Eligibility

Ages Eligible for Study:	up to 21 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00357500

Locations

United States, Connecticut
Connecticut Children's Medical Center
Hartford, Connecticut, United States, 06106
United States, Florida
Miami Children's Hospital
Miami, Florida, United States, 33155-4069
United States, Illinois
Children's Memorial Hospital - Chicago
Chicago, Illinois, United States, 60614
United States, Maine
Maine Medical Center Research Institute
Scarborough, Maine, United States, 04074-7205
United States, Massachusetts
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Minnesota
Children's Hospitals and Clinics of Minnesota - Minneapolis
Minneapolis, Minnesota, United States, 55404
United States, Missouri
St. Louis Children's Hospital
Saint Louis, Missouri, United States, 63110
United States, New Jersey
Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
New Brunswick, New Jersey, United States, 08903
United States, New York
NYU Cancer Institute at New York University Medical Center
New York, New York, United States, 10016
United States, Rhode Island
Hasbro Children's Hospital
Providence, Rhode Island, United States, 02903

Sponsors and Collaborators

Dana-Farber Cancer Institute

Investigators

Study Chair:

Mark W. Kieran, MD, PhD

Dana-Farber Cancer Institute

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Mark William Kieran, Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
ClinicalTrials.gov Identifier:	NCT00357500 History of Changes
Obsolete Identifiers:	NCT00165321
Other Study ID Numbers:	CDR0000487628, DFCI-04343
Study First Received:	July 26, 2006
Last Updated:	March 13, 2010
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

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

Additional relevant MeSH terms:

Leukemia
Lymphoma
Nervous System Neoplasms
Neuroblastoma
Central Nervous System Neoplasms
Neuroectodermal Tumors, Primitive
Neuroectodermal Tumors, Primitive, Peripheral
Sarcoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neoplasms by Site

Nervous System Diseases
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Connective and Soft Tissue
Cyclophosphamide
Thalidomide
Etoposide phosphate
Etoposide
Fenofibrate
Celecoxib
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on February 09, 2012