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

Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00504205
• Other study ID #: SUPERGEN-SGI-0470-01
• Secondary ID: CDR0000556524VPC
• Status: Terminated
• Phase: N/A
• First received: July 17, 2007
• Last updated: August 1, 2013
• Start date: May 2007
• Est. completion date: March 2010

Study information

• Verified date: April 2008
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 30
• Est. completion date: March 2010
• Est. primary completion date: December 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma
• Unspecified Adult Solid Tumor, Protocol Specific

Intervention

Drug:
• multitargeted receptor tyrosine kinase inhibitor MP470

Other:
• laboratory biomarker analysis

• pharmacological study

Procedure:
• positron emission tomography

Locations

Country	Name	City	State
United States	South Texas Accelerated Research Therapeutics	San Antonio	Texas
United States	Virginia G. Piper Cancer Center at Scottsdale Healthcare - Shea	Scottsdale	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Astex Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety			Yes
Primary	Response to treatment according to RECIST criteria			No
Primary	Pharmacodynamic assessments (e.g., changes in phosphorylation of ERK, Rad51 expression, number of CTCs, and tumor glucose metabolism measured by FDG-PET)			No