Etoposide, Cyclophosphamide, Thalidomide, Celecoxib, and Fenofibrate in Relapsed or Progressive Cancer

Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00357500
• Other study ID #: 04-343
• Secondary ID: P30CA006516CDR00
• Status: Completed
• Phase: Phase 2
• First received: July 26, 2006
• Last updated: September 19, 2014
• Start date: January 2005
• Est. completion date: December 2013

Study information

• Verified date: September 2014
• Source: Dana-Farber Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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.

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.

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.

Other known NCT identifiers

• NCT00165321

Recruitment information / eligibility

• Status: Completed
• Enrollment: 101
• Est. completion date: December 2013
• Est. primary completion date: February 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 21 Years

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Central Nervous System Neoplasms
• Central Nervous System Tumor, Pediatric
• Leukemia
• Lymphoma
• Nervous System Neoplasms
• Neuroblastoma
• Sarcoma
• Unspecified Childhood Solid Tumor, Protocol Specific

Intervention

Drug:
• celecoxib

• cyclophosphamide

• etoposide

• fenofibrate

• thalidomide

Locations

Country	Name	City	State
United States	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute	Boston	Massachusetts
United States	Children's Memorial Hospital - Chicago	Chicago	Illinois
United States	Connecticut Children's Medical Center	Hartford	Connecticut
United States	Miami Children's Hospital	Miami	Florida
United States	Children's Hospitals and Clinics of Minnesota - Minneapolis	Minneapolis	Minnesota
United States	Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School	New Brunswick	New Jersey
United States	NYU Cancer Institute at New York University Medical Center	New York	New York
United States	Hasbro Children's Hospital	Providence	Rhode Island
United States	St. Louis Children's Hospital	Saint Louis	Missouri
United States	Maine Medical Center Research Institute	Scarborough	Maine

Sponsors (3)

Lead Sponsor	Collaborator
Dana-Farber Cancer Institute	Children's Hospital Boston, National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

Robison NJ, Campigotto F, Chi SN, Manley PE, Turner CD, Zimmerman MA, Chordas CA, Werger AM, Allen JC, Goldman S, Rubin JB, Isakoff MS, Pan WJ, Khatib ZA, Comito MA, Bendel AE, Pietrantonio JB, Kondrat L, Hubbs SM, Neuberg DS, Kieran MW. A phase II trial of a multi-agent oral antiangiogenic (metronomic) regimen in children with recurrent or progressive cancer. Pediatr Blood Cancer. 2014 Apr;61(4):636-42. doi: 10.1002/pbc.24794. Epub 2013 Oct 4. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Therapy Completion Rate	Proportion of patients alive at 27 weeks without progressive disease (PD) and having tolerated therapy. As appropriate for tumor type and location, gadolinium-enhanced MRI and other imaging modalites were used to assess response. Progressive disease was defined as >/=25% increase in product of diameters, development of new areas of disease, or disease-attributable clinical deterioration or death, progressive disease. 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.	27 weeks	No
Secondary	27-Week Progression-Free Survival	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. As appropriate for tumor type and location, gadolinium-enhanced MRI and other imaging modalites were used to assess response. Progressive disease was defined as >/=25% increase in product of diameters, development of new areas of disease, or disease-attributable clinical deterioration or death, progressive disease. 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.	Assessed every 9 weeks on treatment and annually until death or initiation of new therapy, up to 27 weeks.	No
Secondary	27-Week Overall Survival	27-week overall survival is the probability of patients remaining alive at 27-weeks from study entry estimated using with Kaplan-Meier methods.	Assessed every 9 weeks on treatment and annually until death or initiation of new therapy, up to 27 weeks.	No
Secondary	Best Response	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.	Assessed at study entry, every 9 weeks on treatment and at treatment discontinuation, up to 27 weeks.	No