MP470 in Treating Patients With Unresectable or Metastatic Solid Tumor or Lymphoma

Study Overview
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Brief Summary
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RATIONALE: MP470 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. PURPOSE: This clinical trial is studying the side effects and best dose of MP470 in treating patients with unresectable or metastatic refractory solid tumor, Hodgkin's lymphoma, or non-Hodgkin's lymphoma.

Detailed Description
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OBJECTIVES: Primary Estimate the maximum tolerated dose (MTD) and define the safety profile of multitargeted receptor tyrosine kinase inhibitor MP470 in humans. Secondary Estimate the therapeutic response rate for patients receiving MP470. Define the human pharmacokinetic (PK) and pharmacodynamic (PD) profiles of MP470 capsules Evaluate PK-PD relationships. OUTLINE: This is a multicenter study. Patients receive oral multitargeted receptor tyrosine kinase inhibitor MP470 until the maximum tolerated dose is determined. Pharmacokinetic and pharmacodynamic analyses are carried out to determine changes in phosphorylation of extracellular signal-regulated kinase (ERK), Rad51 expression, number of circulating tumor cells (CTCs), and tumor glucose metabolism measured by 2-[18F]fluoro-2-deoxyglucose positron emission tomography (FDG-PET).

Official Title
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Safety Study to Determine the Maximum Tolerated Dose, Pharmacokinetics and Pharmacodynamics of Oral MP470, a Multi-Targeted Tyrosine Kinase Inhibitor, in Patients With Solid Malignancies

Conditions
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Lymphoma, Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Drug: multitargeted receptor tyrosine kinase inhibitor MP470
* Other: laboratory biomarker analysis
* Other: pharmacological study
* Procedure: positron emission tomography


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Inclusion criteria: Histological or cytological diagnosis of unresectable or metastatic solid-tumor cancer that is refractory to standard therapies OR for which no standard therapy exists Patients with refractory lymphoma (Hodgkin or non-Hodgkin) are also permitted to participate Exclusion criteria: Active CNS metastases (primary brain tumors are permitted) PATIENT CHARACTERISTICS: Inclusion criteria: Karnofsky performance status ≥ 70% Hemoglobin ≥ 9 g/dL ANC ≥ 1.5 × 10^9/L Platelet count ≥ 100 × 10^9/L Total serum bilirubin ≤ 2 mg/dL AST and ALT ≤ 2.5 × ULN (upper limit of normal for the clinical laboratory), but ≤ 5 × ULN is acceptable if due to hepatic metastases Serum albumin ≥ 2 g/dL Serum creatinine ≤ 2 mg/dL LVEF ≥ 50% on ECHO No significant abnormalities on the screening ECG (e.g., left bundle branch block, 3rd degree AV block, acute myocardial infarction or QTc interval > 450 msec) No history of additional risk factors for torsade de pointes (e.g., heart failure, hypokalemia or family history of Long QT Syndrome) Able to swallow MP470 capsules Capable of fasting for 6 hours Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 3 months following completion of study treatment Exclusion criteria: Life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the patient's safety, interfere with the absorption or metabolism of oral MP470, or put the study outcomes at risk Any serious, uncontrolled active infection that requires systemic treatment History of significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, and/or myocardial infarction PRIOR CONCURRENT THERAPY: Inclusion criteria: Recuperated from any prior surgical procedures including at least 4 weeks rest since a major surgery Exclusion criteria: Patient has received any anticancer agent(s) within the past 3 weeks, including investigational agents, chemotherapy (6 weeks for nitrosoureas or mitomycin), immunotherapy, biologic, or hormonal therapy other than luteinizing hormone-releasing hormone (LHRH) agonists Patient has received radiation therapy within the past 4 weeks Patient has a grade 2 or more severe toxicity (other than alopecia) continuing from prior anticancer therapy Patient requires treatment with immunosuppressive agents other than corticosteroids that have been at stable doses for at least 2 weeks

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


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: multitargeted receptor tyrosine kinase inhibitor MP470|nan|
|Other: laboratory biomarker analysis|nan|
|Other: pharmacological study|nan|
|Procedure: positron emission tomography|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety |  |  | 
| Response to treatment according to RECIST criteria |  |  | 
| Pharmacodynamic assessments (e.g., changes in phosphorylation of ERK, Rad51 expression, number of CTCs, and tumor glucose metabolism measured by FDG-PET) |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent small lymphocytic lymphoma, unspecified adult solid tumor, protocol specific, anaplastic large cell lymphoma, angioimmunoblastic T-cell lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, intraocular lymphoma, nodal marginal zone B-cell lymphoma, recurrent adult Burkitt lymphoma, recurrent adult diffuse large cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent adult Hodgkin lymphoma, recurrent adult immunoblastic large cell lymphoma, recurrent adult lymphoblastic lymphoma, recurrent cutaneous T-cell non-Hodgkin lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent mantle cell lymphoma, recurrent marginal zone lymphoma, recurrent mycosis fungoides/Sezary syndrome, splenic marginal zone lymphoma, stage III adult Burkitt lymphoma, stage III adult diffuse large cell lymphoma, stage III adult diffuse mixed cell lymphoma, stage III adult diffuse small cleaved cell lymphoma, stage III adult Hodgkin lymphoma, stage III adult immunoblastic large cell lymphoma, stage III adult lymphoblastic lymphoma, stage III adult T-cell leukemia/lymphoma, stage III cutaneous T-cell non-Hodgkin lymphoma, stage III grade 1 follicular lymphoma, stage III grade 2 follicular lymphoma, stage III grade 3 follicular lymphoma, stage III mantle cell lymphoma, stage III marginal zone lymphoma, stage III mycosis fungoides/Sezary syndrome, stage III small lymphocytic lymphoma, stage IV adult Burkitt lymphoma, stage IV adult diffuse large cell lymphoma, stage IV adult diffuse mixed cell lymphoma, stage IV adult diffuse small cleaved cell lymphoma, stage IV adult Hodgkin lymphoma, stage IV adult immunoblastic large cell lymphoma, stage IV adult lymphoblastic lymphoma, stage IV adult T-cell leukemia/lymphoma, stage IV cutaneous T-cell non-Hodgkin lymphoma, stage IV grade 1 follicular lymphoma, stage IV grade 2 follicular lymphoma, stage IV grade 3 follicular lymphoma, stage IV mantle cell lymphoma, stage IV marginal zone lymphoma, stage IV mycosis fungoides/Sezary syndrome, stage IV small lymphocytic lymphoma, Waldenstrom macroglobulinemia, primary central nervous system non-Hodgkin lymphoma