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

NCT00357500 | Completed Phase 2 Results DMC

• 3 other identifiers: 04-343P30CA006516CDR0000487628
• Study Type: interventional
• Target: 101
• Locations: 1 country
• Sites: 10

Brief 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.

Conditions

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

Keywords

Metronomic; antiangiogenic

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (3)

• 27-Week Progression-Free Survival

  Assessed every 9 weeks on treatment and annually until death or initiation of new therapy, up to 27 weeks.

• 27-Week Overall Survival

  Assessed every 9 weeks on treatment and annually until death or initiation of new therapy, up to 27 weeks.

• Best Response

  Assessed at study entry, every 9 weeks on treatment and at treatment discontinuation, up to 27 weeks.

Study Arms (1)

5-drug metronomic antiangiogenic regimen

EXPERIMENTAL

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

Interventions

celecoxib DRUG

5-drug metronomic antiangiogenic regimen

cyclophosphamide DRUG

5-drug metronomic antiangiogenic regimen

etoposide DRUG

5-drug metronomic antiangiogenic regimen

fenofibrate DRUG

5-drug metronomic antiangiogenic regimen

thalidomide DRUG

5-drug metronomic antiangiogenic regimen

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• National Cancer Institute (NCI): collaborator
• Boston Children's Hospital: collaborator

Study Sites (10)

Connecticut Children's Medical Center

Hartford, Connecticut, 06106, United States

Location

Miami Children's Hospital

Miami, Florida, 33155-4069, United States

Location

Children's Memorial Hospital - Chicago

Chicago, Illinois, 60614, United States

Location

Maine Medical Center Research Institute

Scarborough, Maine, 04074-7205, United States

Location

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

Boston, Massachusetts, 02115, United States

Location

Children's Hospitals and Clinics of Minnesota - Minneapolis

Minneapolis, Minnesota, 55404, United States

Location

St. Louis Children's Hospital

St Louis, Missouri, 63110, United States

Location

Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School

New Brunswick, New Jersey, 08903, United States

Location

NYU Cancer Institute at New York University Medical Center

New York, New York, 10016, United States

Location

Hasbro Children's Hospital

Providence, Rhode Island, 02903, United States

Location

Related 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.

  PMID: 24123865 BACKGROUND

MeSH Terms

Conditions

Central Nervous System Neoplasms; Leukemia; Lymphoma; Neuroblastoma; Sarcoma

Interventions

Celecoxib; Cyclophosphamide; Etoposide; Fenofibrate; Thalidomide

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Neoplasms, Connective and Soft Tissue

Intervention Hierarchy (Ancestors)

Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Fibric Acids; Isobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Phenyl Ethers; Ethers; Benzophenones; Phenols; Ketones; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Piperidones; Piperidines; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Mark Kieran
• Organization: Dana-Farber Cancer Institute

mark_kieran@dfci.harvard.edu

(617) 632-4907

Study Officials

• Mark W. Kieran, MD, PhD

  Dana-Farber Cancer Institute

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 26, 2006
• First Posted: July 27, 2006
• Study Start: January 1, 2005
• Primary Completion: February 1, 2013
• Study Completion: December 1, 2013
• Last Updated: October 1, 2014
• Results First Posted: September 9, 2014

Record last verified: 2014-09

Locations

US (10)