Clinical trial NCT00131937: Sorafenib Tosylate in Treating Patients With Recurrent Aggressive Non-Hodgkin's Lymphoma
Official title: A Phase II Study of Sorafenib (BAY 43-9006) in Recurrent Aggressive Non-Hodgkin's Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Anaplastic Large Cell Lymphoma
Angioimmunoblastic T-cell Lymphoma
Hepatosplenic T-cell Lymphoma
Peripheral T-cell Lymphoma
Recurrent Adult Diffuse Large Cell Lymphoma
Recurrent Adult Immunoblastic Large Cell Lymphoma
Recurrent Adult T-cell Leukemia/Lymphoma
Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2005-08-19
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This phase II trial is studying how well sorafenib works in treating patients with recurrent diffuse large B-cell non-Hodgkin's lymphoma. Sorafenib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.

Detailed description: PRIMARY OBJECTIVES:

I. To evaluate the response rate of treatment with sorafenib (BAY43-9006) in patients with recurrent aggressive non-Hodgkin's lymphomas.

SECONDARY OBJECTIVES:

I. To evaluate the duration of response and progression free survival of treatment with BAY43-9006 in patients with recurrent aggressive Non-Hodgkin's Lymphomas.

II. To characterize the toxicity of treatment with BAY43-9006 in patients with recurrent aggressive Non-Hodgkin's Lymphomas.

III. To further characterize the pharmacokinetics properties of BAY43-9006 and assess influence of monooxygenases polymorphisms and multi-drug resistance transporter (MDR) on pharmacokinetics.

OUTLINE: This is a multicenter study.

Patients receive oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for 1 year.

PLANNED ACCRUAL: 41 ACTUAL ACCRUAL: 14

Eligibility criteria: Inclusion Criteria:

* Patients must have histologically confirmed recurrent de novo or transformed diffuse large B cell lymphoma (DLBCL) or one of its variants according to WHO classification (centroblastic, immunoblastic, T-cell/histiocyte rich and anaplastic variants)
* Eastern Cooperative Oncology Group (ECOG) performance status must be 0 or 1
* Patients must have measurable disease as defined in section 6 assessed within 4 weeks of registration
* Patients must have failed one or more prior Non-Hodgkin lymphoma (NHL) chemotherapy or antibody therapy with curative intent; autologous stem cell transplant is permitted
* Leukocytes \>= 2,000/mm\^3
* Absolute neutrophil count \>= 1,000/mm\^3
* Platelets \>= 75,000/ mm\^3
* Total bilirubin =\< 2.0 X normal institutional limits
* Aspartate Aminotransferase (AST) =\< 2.5 X institutional upper limit of normal
* Alanine Aminotransferase (ALT) =\< 2.5 X institutional upper limit of normal
* Creatinine within normal institutional limits; creatinine clearance calculated or measured at \>= 60 ml/min/1.73m\^2 if creatinine level is above institutional limits
* The prothrombin time (PT)/international normalized ratio (INR) within Institutional limits of normal
* Patients with underlying hypertension as defined by blood pressures averaging greater than 140/90 on two separate clinic visits are eligible if hypertension has been controlled by standard nonpharmacologic and pharmacologic therapy
* Patients must be physically able to orally ingest tablets

Exclusion Criteria:

* Central nervous system (CNS) involvement
* Previously treated with Sorafenib (BAY 43-9006) or other small molecule targeted inhibitors of mitogen-activated protein kinase (MAPK) signaling intermediates or angiogenesis (e.g. bevacizumab)
* Progressed within 60 days of last therapy
* Prior allogeneic stem cell transplant
* Candidates for potentially curative therapy, such as hematopoietic stem cell transplantation (HSCT)
* Currently receiving any other investigational agents
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to sorafenib
* Uncontrolled intercurrent illness including, but not limited to: ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia or psychiatric illness/social situations that would limit compliance with study requirements
* Active HIV infection, because of possible pharmacokinetic interactions of anti-retroviral therapy with BAY43-9006
* Evidence of bleeding diathesis
* Currently taking the cytochrome P450 enzyme-inducing anti-epileptic drugs (phenytoin, carbamazepine and phenobarbital), rifampin or St. John's Wort
* Pregnant or Breast-feeding; all females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy. Women of childbearing potential and sexually active males must be strongly advised to use an accepted and effective method of contraception

Primary outcomes:
measure: Overall Response (OR) Rate
timeFrame: Assessed at the end of Cycle 2 and Cycle 6 (1 cycle = 28 days). Then every 3 months beginning Cycle 9 if patient is < 2 years from study entry, every 6 months if patient is 2-3 years from study entry, up to 3 years.
Secondary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: Assessed after month 2 and month 6, then every 3 months if patient is < 2 years from study entry, every 6 months if patient is 2-3 years from study entry, up to 3 years
measure: Overall Survival
timeFrame: Assessed after month 2 and month 6, then every 3 months if patient is < 2 years from study entry, every 6 months if patient is 2-3 years from study entry, up to 3 years.
Other outcomes:
Locations:
city: Boston
country: United States
facility: Eastern Cooperative Oncology Group
state: Massachusetts
Study officials:
affiliation: Eastern Cooperative Oncology Group
name: Sandra Horning
role: PRINCIPAL_INVESTIGATOR
References: