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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


N/A
18 Years
N/A
Not Enrolling
Both
Lymphoma, Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

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


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).

Inclusion 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

Type of Study:

Interventional

Study Design:

Primary Purpose: Treatment

Outcome Measure:

Safety

Safety Issue:

Yes

Principal Investigator

Gregory Berk, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Astex Pharmaceuticals

Authority:

Unspecified

Study ID:

CDR0000556524

NCT ID:

NCT00504205

Start Date:

May 2007

Completion Date:

Related Keywords:

  • Lymphoma
  • Unspecified Adult Solid Tumor, Protocol Specific
  • 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
  • Lymphoma
  • Lymphoma, Non-Hodgkin
  • Lymphoma, Large-Cell, Immunoblastic

Name

Location

Virginia G. Piper Cancer Center at Scottsdale Healthcare - SheaScottsdale, Arizona  85260
South Texas Accelerated Research TherapeuticsSan Antonio, Texas  78229