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

Primary Purpose

Lymphoma, Unspecified Adult Solid Tumor, Protocol Specific

Status
Terminated
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
multitargeted receptor tyrosine kinase inhibitor MP470
laboratory biomarker analysis
pharmacological study
positron emission tomography
Sponsored by
Astex Pharmaceuticals, Inc.
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lymphoma focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Virginia G. Piper Cancer Center at Scottsdale Healthcare - Shea
  • South Texas Accelerated Research Therapeutics

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

Full Information

First Posted
July 17, 2007
Last Updated
August 1, 2013
Sponsor
Astex Pharmaceuticals, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT00504205
Brief Title
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

2. Study Status

Record Verification Date
April 2008
Overall Recruitment Status
Terminated
Why Stopped
Withdrawn as trial was never activated by SuperGen
Study Start Date
May 2007 (undefined)
Primary Completion Date
December 2008 (Actual)
Study Completion Date
March 2010 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Astex Pharmaceuticals, Inc.

4. Oversight

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
multitargeted receptor tyrosine kinase inhibitor MP470
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Type
Other
Intervention Name(s)
pharmacological study
Intervention Type
Procedure
Intervention Name(s)
positron emission tomography
Primary Outcome Measure Information:
Title
Safety
Title
Response to treatment according to RECIST criteria
Title
Pharmacodynamic assessments (e.g., changes in phosphorylation of ERK, Rad51 expression, number of CTCs, and tumor glucose metabolism measured by FDG-PET)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gregory Berk, MD
Organizational Affiliation
Astex Pharmaceuticals, Inc.
Official's Role
Study Chair
Facility Information:
Facility Name
Virginia G. Piper Cancer Center at Scottsdale Healthcare - Shea
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85258-4512
Country
United States
Facility Name
South Texas Accelerated Research Therapeutics
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States

12. IPD Sharing Statement

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

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