Imatinib Mesylate in Treating Patients With Advanced Cancer and Liver Dysfunction

Unspecified Adult Solid Tumor, Protocol Specific Clinical Trial

Official title:

A Phase I Pharmacokinetic Study of STI571 in Patients With Advanced Malignancies and Varying Levels of Liver Dysfunction

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00025415
• Other study ID #: NCI-2012-02418
• Secondary ID: 01-028U01CA09916
• Status: Completed
• Phase: Phase 1
• First received: October 11, 2001
• Last updated: February 6, 2013
• Start date: August 2001

Study information

• Verified date: February 2013
• 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

Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Phase I trial to study the effectiveness of imatinib mesylate in treating patients who have advanced cancer and liver dysfunction

Description:

PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose and dose-limiting toxicity of imatinib mesylate in patients with advanced malignancies and varying degrees of liver dysfunction.

II. Determine the effects of hepatic dysfunction on the pharmacodynamics and pharmacokinetics of this drug in these patients.

III. Determine the non-dose-limiting toxic effects of this drug in these patients.

IV. Determine the response rate of these patients treated with this drug. V. Correlate the Childs-Pugh classification of hepatic dysfunction with observed toxic effects, pharmacodynamics, and pharmacokinetics of this drug in these patients.

OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to liver dysfunction (normal vs mild vs moderate vs severe).

Patients receive oral imatinib mesylate daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients within each stratum (except normal stratum) receive escalating doses of imatinib mesylate until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study within 1 year.

Other known NCT identifiers

• NCT00025948

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. primary completion date: January 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 15 Years and older

Eligibility

Inclusion Criteria:

• Histologically or cytologically confirmed surgically incurable solid tumor orhematologic malignancy for which no standard or palliative therapy exists oris no longer effective

• All tumor types are eligible, including:

• Chronic myelogenous leukemia or other Philadelphia chromosome-positive leukemia OR

• Gastrointestinal stromal tumors

• Patients with gliomas that require corticosteroids or anticonvulsants must beon a stable dose and seizure-free for 1 month

• No unstable or untreated (non-irradiated) brain metastases

• Performance status - ECOG 0-2

• Performance status - Karnofsky 60-100%

• More than 3 months

• WBC at least 3,000/mm^3

• Absolute neutrophil count at least 1,500/mm^3

• Platelet count at least 100,000/mm^3

• No active hemolysis

• See Surgery

• No evidence of biliary sepsis

• Creatinine normal

• Creatinine clearance at least 60 mL/min

• No symptomatic congestive heart failure

• No unstable angina pectoris

• No cardiac arrhythmia

• Able to swallow pills

• No other uncontrolled concurrent illness that would preclude study participation

• No ongoing or active infection

• No uncontrolled diarrhea

• No psychiatric illness or social situation that would preclude study compliance

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective barrier contraception during and for 6 months after study completion

• At least 24 hours since prior colony-stimulating factors

• No concurrent colony-stimulating factors

• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered

• See Disease Characteristics

• See Disease Characteristics

• At least 4 weeks since prior radiotherapy and recovered

• See Disease Characteristics

• At least 10 days since prior placement of shunt for treatment of biliary obstruction

• At least 14 days since prior major surgery

• No prior solid organ transplantation

• No other concurrent investigational agents

• No concurrent therapeutic doses of warfarin for anticoagulation

• No other concurrent investigational or commercial agents or therapies for treatment of this disease

• No concurrent combination antiretroviral therapy for HIV-positive patients

• No concurrent acetaminophen of more than 4,000 mg/day

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Accelerated Phase Chronic Myelogenous Leukemia
• Acute Undifferentiated Leukemia
• AIDS-related Peripheral/Systemic Lymphoma
• AIDS-related Primary CNS Lymphoma
• Amyloidosis
• Anaplastic Large Cell Lymphoma
• Angioimmunoblastic T-cell Lymphoma
• Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative
• Blast Crisis
• Blastic Phase Chronic Myelogenous Leukemia
• Burkitt Lymphoma
• Childhood Myelodysplastic Syndromes
• Chronic Eosinophilic Leukemia
• Chronic Myelogenous Leukemia, BCR-ABL1 Positive
• Chronic Myelomonocytic Leukemia
• Chronic Neutrophilic Leukemia
• Chronic Phase Chronic Myelogenous Leukemia
• de Novo Myelodysplastic Syndromes
• Essential Thrombocythemia
• Extramedullary Plasmacytoma
• Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
• Gastrointestinal Stromal Tumor
• Gastrointestinal Stromal Tumors
• Hodgkin Disease
• Hypereosinophilic Syndrome
• Intraocular Lymphoma
• Isolated Plasmacytoma of Bone
• Leukemia
• Leukemia, Hairy Cell
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative
• Leukemia, Myeloid, Chronic-Phase
• Leukemia, Myelomonocytic, Acute
• Leukemia, Myelomonocytic, Chronic
• Leukemia, Prolymphocytic
• Leukemia, T-Cell
• Leukemia-Lymphoma, Adult T-Cell
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, B-Cell, Marginal Zone
• Lymphoma, Follicular
• Lymphoma, Large B-Cell, Diffuse
• Lymphoma, Large-Cell, Anaplastic
• Lymphoma, Large-Cell, Immunoblastic
• Lymphoma, Mantle-Cell
• Lymphoma, Non-Hodgkin
• Lymphoma, T-Cell
• Lymphoma, T-Cell, Cutaneous
• Meningeal Chronic Myelogenous Leukemia
• Monoclonal Gammopathy of Undetermined Significance
• Multiple Myeloma
• Mycoses
• Mycosis Fungoides
• Myelodysplastic Syndromes
• Myelodysplastic-Myeloproliferative Diseases
• Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable
• Myeloproliferative Disorders
• Neoplasm Metastasis
• Nodal Marginal Zone B-cell Lymphoma
• Paraproteinemias
• Plasmacytoma
• Polycythemia
• Polycythemia Vera
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Preleukemia
• Previously Treated Myelodysplastic Syndromes
• Primary Central Nervous System Non-Hodgkin Lymphoma
• Primary Myelofibrosis
• Primary Systemic Amyloidosis
• Progressive Hairy Cell Leukemia, Initial Treatment
• Prolymphocytic Leukemia
• Recurrent Adult Acute Lymphoblastic Leukemia
• Recurrent Adult Acute Myeloid Leukemia
• 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 Adult T-cell Leukemia/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
• Refractory Chronic Lymphocytic Leukemia
• Refractory Hairy Cell Leukemia
• Refractory Multiple Myeloma
• Relapsing Chronic Myelogenous Leukemia
• Secondary Acute Myeloid Leukemia
• Secondary Myelodysplastic Syndromes
• Sezary Syndrome
• Small Intestine Lymphoma
• Splenic Marginal Zone 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 Chronic Lymphocytic Leukemia
• 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
• Syndrome
• T-cell Large Granular Lymphocyte Leukemia
• Thrombocythemia, Essential
• Thrombocytosis
• Unspecified Adult Solid Tumor, Protocol Specific
• Untreated Adult Acute Lymphoblastic Leukemia
• Untreated Adult Acute Myeloid Leukemia
• Untreated Hairy Cell Leukemia
• Waldenstrom Macroglobulinemia
• Waldenström Macroglobulinemia

Intervention

Drug:
• imatinib mesylate
Given orally

Other:
• pharmacological study
Correlative studies

Locations

Country	Name	City	State
United States	University of Pittsburgh	Pittsburgh	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	MTD defined based on the toxicities observed during the first cycle of treatment		4 weeks	Yes
Primary	Toxicity evaluation graded according to the NCI common toxicity criteria and relationship to the study drug	Results will be tabulated by liver dysfunction group.	Up to 4 years	No
Secondary	Pharmacokinetic data	Will be analyzed with ADAPT II, and results will be summarized separately for the four study groups. Additionally, results for pharmacokinetic parameters will be related to the measured level of liver dysfunction in exploratory analyses.	Day 1, 2, 3, 4, 15, 16	No
Secondary	Responses	Will be tabulated by liver dysfunction group, and by dose if appropriate.	Up to 4 years	No
Secondary	Child-Pugh Classification	Will be correlated to the toxicities, pharmacokinetic and pharmacodynamic data seen with STI571.	Baseline	No