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

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.

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).

Eligibility Criteria:
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