Etoposide, Cyclophosphamide, Thalidomide, Celecoxib, and Fenofibrate in Relapsed or Progressive Cancer
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.
Central Nervous System Tumor, Pediatric
Unspecified Childhood Solid Tumor, Protocol Specific
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
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|
- Therapy Completion Rate [ Time Frame: 27 weeks ] [ Designated as safety issue: No ]Proportion of patients alive at 27 weeks without progression and tolerated therapy.
- 27-Week Progression-Free Survival [ Time Frame: Assessed every 9 weeks on treatment and annually until death or initiation of new therapy. ] [ Designated as safety issue: No ]27-week progression-free survival is the probability of patients remaining alive and progression-free at 27-weeks from study entry estimated using Kaplan-Meier methods.
- 27-Week Overall Survival [ Time Frame: Assessed every 9 weeks on treatment and annually until death or initiation of new therapy. ] [ Designated as safety issue: No ]27-week progression-free survival is the probability of patients remaining alive at 27-weeks from study entry estimated using with Kaplan-Meier methods.
- Best Response [ Time Frame: Assessed at study entry, every 9 weeks on treatment and at treatment discontinuation. ] [ Designated as safety issue: No ]As appropriate for tumor type and location, gadolinium-enhanced MRI and other imaging modalites were used to assess response. Best response was regarded as best response at any single assessment. Response was defined as follows: complete resolution of all demonstrable tumor, complete response (CR); >50% decrease in the product of the 2 maximum perpendicular diameters relative to the baseline evaluation, partial response (PR); <50% decrease and <25% increase in product of diameters, stable disease (SD); and ≥25% increase in product of diameters, development of new areas of disease, or disease-attributable clinical deterioration or death, progressive disease (PD). For patients with leukemia PD was defined as >25% or >5,000 cells/mm3 increase in number of circulating cells, development of extramedullary disease, or other clinical evidence of progression.
|Study Start Date:||January 2005|
|Study Completion Date:||December 2013|
|Primary Completion Date:||February 2013 (Final data collection date for primary outcome measure)|
Experimental: 5-drug metronomic antiangiogenic regimen
Thalidomide: Start at 3 mg/kg (rounded to nearest 50 mg), increasing dose weekly by 50 mg as tolerated to 24 mg/kg (max 1,000 mg); Celecoxib: < 20 kg at 100 mg; 20-50 kg at 200 mg; > 50 kg at 400 mg; Fenofibrate: 90 mg/m2 (max 200 mg); Etoposide: 50 mg/m2; Cyclophosphamide: 2.5 mg/kg (max 100 mg); 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).
|Drug: celecoxib Drug: cyclophosphamide Drug: etoposide Drug: fenofibrate Drug: thalidomide|
- 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.
- 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.
STATISTICAL DESIGN: Patients were classified into one of 8 strata according to diagnosis: leukemia/lymphoma, bone tumors, neuroblastoma, high grade glial tumors, low grade glial tumors, ependymoma, medulloblastoma/PNET, and miscellaneous. A two-stage design for each disease stratum was planned. The accrual goal at the end of the two-stage design was 20 subjects for each stratum. A stopping rule was applied after the accrual of the first 10 eligible subjects enrolled in each disease stratum. If 1 or more patients in the first 10 evaluable patients were alive and progression-free at 27 weeks and have tolerated therapy then accrual to stage two would proceed. Among 20 patients within a stratum, if 3 or more patients met primary endpoint then regimen would be considered successful. The probability of concluding the treatment is feasible is 0.95 if true success rate is 30% and 0.07 if true succes rate is 5%. Overall accrual target was 80-160 patients. Please see published manuscript (Robison et al Pediatr Blood Cancer 2014) for results within disease strata.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00357500
|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|
|Study Chair:||Mark W. Kieran, MD, PhD||Dana-Farber Cancer Institute|