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

Study Overview
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Brief Summary
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Sorafenib may stop the growth of cancer cells by blocking blood flow to the cancer and by blocking some of the enzymes needed for cell growth. This phase II trial is studying how well sorafenib works in treating patients with chemosensitive recurrent aggressive non-Hodgkin's lymphoma

Detailed Description
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PRIMARY OBJECTIVES: I. Determine the overall response rate, including complete and partial responses, in patients with chemosensitive, relapsed, aggressive, non-Hodgkin's lymphoma treated with sorafenib. SECONDARY OBJECTIVES: I. Determine progression-free and overall survival of patients treated with this drug. II. Determine response duration in patients treated with this drug. OUTLINE: This is an open-label study. Patients receive oral sorafenib twice daily in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically. PROJECTED ACCRUAL: A total of 33 patients will be accrued for this study.

Official Title
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A Phase 2 Study of BAY 43-9006 (IND 69896) in Chemosensitive Relapsed Aggressive Non-Hodgkin's Lymphomas

Conditions
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Anaplastic Large Cell Lymphoma, Recurrent Adult Diffuse Large Cell Lymphoma, Recurrent Mantle Cell Lymphoma

Intervention / Treatment
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* Drug: sorafenib tosylate
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed aggressive* non-Hodgkin's lymphoma by excisional-node biopsy or core needle biopsy and bone marrow biopsy, including 1 of the following types: Mantle cell lymphoma Primary mediastinal large B-cell lymphoma Diffuse large B-cell lymphoma Anaplastic large cell lymphoma (T-cell or null-cell type) Recurrent disease Patients must have received ≥ 1 induction regimen containing anthracyclines (e.g., CHOP [with or without rituximab] or R-EPOCH) Chemosensitive disease at the time of relapse Patients who responded with a complete or partial remission that lasted at least 8 weeks after their last chemotherapy regimen are considered chemosensitive Measurable disease, defined as a lymph node or a nodal mass of > 1 cm in its longest transverse diameter on CT scan Ineligible for, refused, or relapsed after stem cell transplant (for patients with non-mantle cell lymphoma) No known brain metastases, including meningeal involvement ECOG performance status (PS) 0-2 Karnofsky PS 60-100% Life expectancy > 3 months WBC ≥ 3,000/mm^3 Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Bilirubin normal AST and ALT ≤ 2.5 times upper limit of normal Creatinine normal OR creatinine clearance ≥ 60 mL/min Fertile patients must use effective contraception Not pregnant or nursing Negative pregnancy test No uncontrolled illness No history of allergic reactions attributed to compounds of similar chemical or biologic composition to sorafenib No known positive HIV serology No inflammatory bowel disease No swallowing dysfunction that would prevent ingestion of pills No hemorrhagic diathesis No ongoing or active infection No symptomatic congestive heart failure No unstable angina pectoris No cardiac arrhythmia No uncontrolled hypertension No psychiatric or social situation that would limit compliance with study requirements No poorly controlled medical condition that would seriously complicate compliance with this study Patients with inflammatory or exfoliative skin disease are excluded (regardless of the extent of the involvement) unless the skin condition is lymphoma related See Disease Characteristics Previous treatment-related toxic effects should be resolved to grade 1 or better No chemotherapy or radiation therapy within the past 4 weeks 6 weeks for nitrosoureas or mitomycin C No prior antibody therapy for at least 3 months Prior radiation for localized disease or total body irradiation as part of a conditioning regimen prior to stem cell transplant allowed Prior radio-immunotherapy allowed No concurrent therapeutic anticoagulation Prophylactic anticoagulation (i.e., low-dose warfarin) of venous or arterial access devices are acceptable provided that the requirements for PT, INR, and PTT are met No concurrent use of another investigational agent No concurrent use of the following drugs: phenytoin, carbamazepine, phenobarbital, rifampin, or Hypericum perforatum (St. John's wort) No other concurrent anticancer therapy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (sorafenib tosylate)<br>Patients receive oral sorafenib twice daily in the absence of disease progression or unacceptable toxicity. | Drug: sorafenib tosylate<br>* Given orally<br>* Other names: SFN;Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (complete and partial response) | Will be calculated as the percent of evaluable patients whose best response is a CR or PR. The exact binomial method will be used to determine the confidence interval of response rate. | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | The Kaplan-Meier product-limit method will be used in analysis of survival time. | Up to 2 years | 
| Time to disease progression | The Kaplan-Meier product-limit method will be used in analysis of time to disease progression. | Up to 2 years |