Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Closed	21 and under	Other	DFCI-04343 04-343, NCT00357500

Objectives

Primary

1. 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

1. Determine, preliminarily, the biologic activity of this regimen, in terms of tumor response and overall survival, in these patients.
2. Determine the toxicity of this regimen in these patients.
3. Evaluate different radiographic techniques as markers of tumor response in these patients.
4. Evaluate the predictive ability of in vitro correlative studies as markers of tumor response.

Entry 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

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

Patient Characteristics:

• Karnofsky performance status 50-100% OR Lansky play scale 50-100% (for infants)
• Life expectancy > 2 months
• Platelet count > 75,000/mm³ (transfusion independent)
• Absolute neutrophil count > 1,000/mm³ (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

Expected Enrollment

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

Outcomes

Time to disease progression

Tumor response
Overall survival
Progression-free survival
Toxicity
Different radiographic techniques as markers of response
Biological markers as markers of response/angiogenesis

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.

Trial Contact Information

Trial Lead Organizations

Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute

Mark Kieran, MD, PhD, Protocol chair		Ph: 617-632-4907; 866-790-4500

Registry Information
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
Trial Start Date		2005-01-07
Trial Completion Date		2009-07-31 (estimated)
Registered in ClinicalTrials.gov		NCT00357500
Date Submitted to PDQ		2006-05-23
Information Last Verified		2009-07-07
NCI Grant/Contract Number		CA06516

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