Sorafenib Tosylate in Treating Patients With Recurrent Aggressive Non-Hodgkin's Lymphoma

National Cancer Institute (NCI)

Status and phase: Completed; Phase 2

Conditions: Recurrent Adult Immunoblastic Large Cell Lymphoma; Hepatosplenic T-cell Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Angioimmunoblastic T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Peripheral T-cell Lymphoma

Treatments: Drug: sorafenib tosylate

Study type: Interventional

Funder types: NIH

Identifiers

NCT00131937

E1404 (Other Identifier)

NCI-2014-00658

U10CA021115 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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

Enrollment: 14 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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14 participants in 1 patient group

Treatment (sorafenib tosylate)

Experimental group

Description:

Patients receive oral sorafenib 400 mg PO twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Treatment:

Drug: sorafenib tosylate