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

August 1, 2013 updated by: Astex Pharmaceuticals, Inc.

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

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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).

Study Type

Interventional

Enrollment (Anticipated)

30

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arizona
      • Scottsdale, Arizona, United States, 85258-4512
        • Virginia G. Piper Cancer Center at Scottsdale Healthcare - Shea
    • Texas
      • San Antonio, Texas, United States, 78229
        • South Texas Accelerated Research Therapeutics

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure
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)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Astex Pharmaceuticals, Inc.

Investigators

  • Study Chair: Gregory Berk, MD, Astex Pharmaceuticals, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2007

Primary Completion (Actual)

December 1, 2008

Study Completion (Actual)

March 1, 2010

Study Registration Dates

First Submitted

July 17, 2007

First Submitted That Met QC Criteria

July 17, 2007

First Posted (Estimate)

July 19, 2007

Study Record Updates

Last Update Posted (Estimate)

August 2, 2013

Last Update Submitted That Met QC Criteria

August 1, 2013

Last Verified

April 1, 2008

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SUPERGEN-SGI-0470-01
  • CDR0000556524 (Registry Identifier: PDQ (Physician Data Query))
  • VPCCS-SGI-0470-01

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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