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

Condition(s) targeted: Brain and Central Nervous System Tumors; Leukemia; Lymphoma; Neuroblastoma; Sarcoma; Unspecified Childhood Solid Tumor, Protocol Specific

Intervention: celecoxib (Drug); cyclophosphamide (Drug); etoposide (Drug); fenofibrate (Drug); thalidomide (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: Dana-Farber Cancer Institute

Official(s) and/or principal investigator(s):
Mark W. Kieran, MD, PhD, Study Chair, Affiliation: Dana-Farber Cancer Institute

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.

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

Study design: Treatment

Primary outcome: Time to disease progression

Secondary outcome:

Tumor response

Overall survival

Progression-free survival

Toxicity

Different radiographic techniques as markers of response

Biological markers as markers of response/angiogenesis

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.

Minimum age: N/A. Maximum age: 21 Years. Gender(s): Both.

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

Connecticut Children's Medical Center, Hartford, Connecticut 06106, United States; Recruiting
Clinical Trials Office - Connecticut Children's Medical Center, Phone: 860-545-9967

Miami Children's Hospital, Miami, Florida 33155-4069, United States; Recruiting
Ziad Khatib, MD, Phone: 305-666-6511, Email: ziad.khatib@mch.com

Children's Memorial Hospital - Chicago, Chicago, Illinois 60614, United States; Recruiting
Stewart Goldman, MD, Phone: 773-880-4585

Maine Medical Center Research Institute, Scarborough, Maine 04074-7205, United States; Recruiting
S. Ashley Speckhart, MD, Phone: 207-885-7565

Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute, Boston, Massachusetts 02115, United States; Recruiting
Mark W. Kieran, MD, PhD, Phone: 617-632-4907

Children's Hospitals and Clinics of Minnesota - Minneapolis, Minneapolis, Minnesota 55404, United States; Recruiting
Clinical Trials Office - Children's Hospitals and Clinics of M, Phone: 612-813-5193

St. Louis Children's Hospital, Saint Louis, Missouri 63110, United States; Recruiting
Joshua Rubin, MD, PhD, Phone: 314-286-2790

Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School, New Brunswick, New Jersey 08903, United States; Recruiting
Clinical Trials Office - Cancer Institute of New Jersey, Phone: 732-235-8675

NYU Cancer Institute at New York University Medical Center, New York, New York 10016, United States; Recruiting
Jeffrey C. Allen, MD, Phone: 212-263-6485

Hasbro Children's Hospital, Providence, Rhode Island 02903, United States; Recruiting
Clinical Trials Office - Hasbro Children's Hospital, Phone: 401-444-8945

Clinical trial summary from the National Cancer Institute's PDQ® database

Starting date: January 2005
Last updated: December 16, 2008