Celecoxib in Patients With Newly Diagnosed GBM Who Are Receiving Anticonvulsant Drugs and Undergoing RT

Johns Hopkins Medicine

Status and phase: Terminated; Phase 2

Conditions: Brain and Central Nervous System Tumors

Treatments: Radiation: radiation therapy; Drug: Celecoxib

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00068770

NABTT-2100

U01CA062475 (U.S. NIH Grant/Contract)

JHOC-NABTT-2100

NABTT-2100 CDR0000328117

Details and patient eligibility

About

RATIONALE: Celecoxib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. It is not yet known whether the effectiveness of celecoxib in treating glioblastoma multiforme is decreased in patients who are receiving anticonvulsant drugs and undergoing radiation therapy.

PURPOSE: Phase II trial to study the effectiveness of celecoxib in treating patients who are receiving anticonvulsant drugs and undergoing radiation therapy for newly diagnosed glioblastoma multiforme.

Full description

OBJECTIVES:

Primary

• Determine the effects of hepatic enzyme-inducing drugs, such as anticonvulsants, on the pharmacokinetics of celecoxib in patients with newly diagnosed glioblastoma multiforme undergoing radiotherapy.
• Determine the effects of steroids on the pharmacokinetics of celecoxib in these patients.

Secondary

• Determine the safety of celecoxib in these patients.
• Determine the duration of survival of patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients are assigned to 1 of 2 groups based on anticonvulsant therapy.

• Group A: Patients treated with any of the following anticonvulsant drugs that induce hepatic metabolic enzymes:

  • Phenytoin
  • Carbamazepine
  • Phenobarbital
  • Primidone
  • Oxcarbazepine

• Group B: Patients treated with any of the following anticonvulsant drugs that cause modest or no induction of hepatic metabolic enzymes OR no anticonvulsant drug:

  • Gabapentin
  • Lamotrigine
  • Valproic acid
  • Levetiracetam
  • Tiagabine
  • Topiramate
  • Zonisamide
  • Felbamate

• Induction therapy: Patients in both groups receive oral celecoxib twice* daily on weeks 1-11 and undergo radiotherapy 5 days a week on weeks 2-7.

• Maintenance therapy: Patients receive oral celecoxib twice daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

NOTE: *Patients receive only 1 dose on the first day of celecoxib administration.

Patients are followed every 2 months.

PROJECTED ACCRUAL: A total of 44 patients (22 per group) will be accrued for this study within approximately 8 months.

Enrollment: 35 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed glioblastoma multiforme

  • Supratentorial
  • Grade IV astrocytoma

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Karnofsky 60-100%

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 9.0 g/dL

Hepatic

• Bilirubin no greater than 1.5 mg/dL
• Transaminases no greater than 4 times upper limit of normal

Renal

• Creatinine no greater than 1.7 mg/dL
• Creatinine clearance at least 60 mL/min
• No prior renal toxicity with nonsteroidal anti-inflammatory drugs

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Mini mental score at least 15
• No history of peptic disease
• No serious concurrent infection
• No other medical illness that would preclude study participation
• No other malignancy within the past 5 years except curatively treated carcinoma in situ or basal cell skin cancer
• No allergy to sulfonamides
• Able to tolerate cyclo-oxygenase-2 (COX-2) inhibitors

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior immunotherapy or biologic agents for the malignancy, including any of the following:

  • Immunotoxins
  • Immunoconjugates
  • Antisense agents
  • Peptide receptor antagonists
  • Interferons
  • Interleukins
  • Tumor-infiltrating lymphocytes
  • Lymphokine-activated killer cells
  • Gene therapy

• No concurrent prophylactic growth factors (e.g., filgrastim [G-CSF] or sargramostim [GM-CSF])

Chemotherapy

• No prior chemotherapy for the malignancy

Endocrine therapy

• No prior hormonal therapy for the malignancy
• Prior glucocorticoid therapy allowed
• Concurrent corticosteroids allowed provided there has been no dose increase within the past 5 days

Radiotherapy

• No prior radiotherapy for the malignancy

Surgery

• Recovered from prior surgery

Other

• At least 1 week since prior fluconazole
• More than 10 days since prior anticonvulsant drugs that induce hepatic metabolic enzymes (Group A)
• No other prior therapy for the malignancy
• No concurrent enrollment in another therapeutic clinical trial
• No concurrent fluconazole

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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35 participants in 2 patient groups

p450 ( +EIASD)

Active Comparator group

Description:

on p450 inhibitor (Patients taking anttiseizure drugs that are known to induce the hepatic drug-metabolizing enzymes - including phenytoin, carbamazepine, phenobarbital, primidone and oxcarbazepine) celecoxib and radiation therapy will be adminstered with this arm

Treatment:

Drug: Celecoxib

Radiation: radiation therapy

nonp450 (-EIASD)

Active Comparator group

Description:

not on p450 inhibitor (Patients either NOT taking anti-seizure drugs or ones that are known to not significantly influence the hepatic drug-metabolizing enzymes - including gabapentin, lamotrigine, valproic acid, levetiracetam, tiagabine,topiramate, zonisamide and filbamate. celecoxib and radiation therapy will be adminstered with this arm

Treatment:

Drug: Celecoxib

Radiation: radiation therapy