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

This study has been terminated.
(Withdrawn as trial was never activated by SuperGen)
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00504205
First received: July 17, 2007
Last updated: August 1, 2013
Last verified: April 2008
  Purpose

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.


Condition Intervention
Lymphoma
Unspecified Adult Solid Tumor, Protocol Specific
Drug: multitargeted receptor tyrosine kinase inhibitor MP470
Other: laboratory biomarker analysis
Other: pharmacological study
Procedure: positron emission tomography

Study Type: Interventional
Study Design: Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Safety [ Designated as safety issue: Yes ]
  • Response to treatment according to RECIST criteria [ Designated as safety issue: No ]
  • Pharmacodynamic assessments (e.g., changes in phosphorylation of ERK, Rad51 expression, number of CTCs, and tumor glucose metabolism measured by FDG-PET) [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: May 2007
Study Completion Date: March 2010
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00504205

Locations
United States, Arizona
Virginia G. Piper Cancer Center at Scottsdale Healthcare - Shea
Scottsdale, Arizona, United States, 85258-4512
United States, Texas
South Texas Accelerated Research Therapeutics
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
Astex Pharmaceuticals
Investigators
Study Chair: Gregory Berk, MD Astex Pharmaceuticals
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00504205     History of Changes
Other Study ID Numbers: SUPERGEN-SGI-0470-01, CDR0000556524, VPCCS-SGI-0470-01
Study First Received: July 17, 2007
Last Updated: August 1, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
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

Additional relevant MeSH terms:
Lymphoma
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on October 21, 2014