Clinical trial NCT00504205: MP470 in Treating Patients With Unresectable or Metastatic Solid Tumor or Lymphoma
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Lymphoma
Unspecified Adult Solid Tumor, Protocol Specific
Keywords: 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
recurrent small lymphocytic lymphoma
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
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2007-07-19
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: 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: 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

Primary outcomes:
measure: Safety
measure: Response to treatment according to RECIST criteria
measure: Pharmacodynamic assessments (e.g., changes in phosphorylation of ERK, Rad51 expression, number of CTCs, and tumor glucose metabolism measured by FDG-PET)
Secondary outcomes:
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Virginia G. Piper Cancer Center at Scottsdale Healthcare - Shea
state: Arizona
city: San Antonio
country: United States
facility: South Texas Accelerated Research Therapeutics
state: Texas
Study officials:
affiliation: Astex Pharmaceuticals, Inc.
name: Gregory Berk, MD
role: STUDY_CHAIR
References: