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

This study is currently recruiting participants.
Verified March 2013 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00608361
First received: January 30, 2008
Last updated: March 26, 2013
Last verified: March 2013
  Purpose

This phase I trial is studying the side effects and best dose of dasatinib in treating patients with metastatic or unresectable solid tumor or lymphoma. Dasatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.


Condition Intervention Phase
Adult Nasal Type Extranodal NK/T-cell Lymphoma
Adult Primary Hepatocellular Carcinoma
Advanced Adult Primary Liver Cancer
Anaplastic Large Cell Lymphoma
Angioimmunoblastic T-cell Lymphoma
Cutaneous B-cell Non-Hodgkin Lymphoma
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
Intraocular Lymphoma
Nodal Marginal Zone B-cell Lymphoma
Primary Central Nervous System Hodgkin Lymphoma
Primary Central Nervous System Non-Hodgkin 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 Grade III Lymphomatoid Granulomatosis
Recurrent Adult Hodgkin Lymphoma
Recurrent Adult Immunoblastic Large Cell Lymphoma
Recurrent Adult Lymphoblastic Lymphoma
Recurrent Adult Primary Liver Cancer
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
Small Intestine 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
Unspecified Adult Solid Tumor, Protocol Specific
Waldenström Macroglobulinemia
Drug: dasatinib
Other: pharmacological study
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Pharmacokinetic Study of Dasatinib (BMS-354825) (NSC-732517; IND-73969) in Patients With Advanced Malignancies and Varying Levels of Liver Dysfunction

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Maximum tolerated dose, defined as the highest dose level at which less than 33% of 6-9 evaluable patients experience DLT [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
    Toxicity will graded according to the NCI CTCAE v3.0.

  • Pharmacokinetic parameters AUC(to infinity), AUC(to 24 hours), and Cmax [ Time Frame: Days 1 and 8 of course 1 ] [ Designated as safety issue: No ]
    Analyzed in the natural log scale. For each PK parameter, the mean difference between the recommended dose for a liver impairment group and the normal liver function group dosed at 140 mg OD (equivalent to ratios of geometric means in the non-log scale) will be tested against 0 at a one-sided 0.05 significance level to detect an increase in the liver impairment group (equivalent to a 2-sided 90% confidence interval).


Estimated Enrollment: 45
Study Start Date: October 2008
Estimated Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (dasatinib)

Patients receive dasatinib PO once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating dose of dasatinib until the 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. At least 6 patients are treated at the MTD.

Drug: dasatinib
Given PO
Other Names:
  • BMS-354825
  • Sprycel
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To estimate the maximum tolerated dose of dasatinib in patients with varying degrees of hepatic impairment.

II. To estimate the pharmacokinetic (PK) profile of this drug in these patients.

III. To assess the safety profile and dose-limiting toxicities (if any) of this drug in these patients.

SECONDARY OBJECTIVES:

I. To describe any antitumor efficacy associated with this drug in these patients.

II. To examine whether the PK clearance of dasatinib correlates with hepatic function as assessed by Child-Pugh Criteria, the NCI Organ Dysfunction Working Group Criteria, or other assessments of liver function such as total bilirubin level.

OUTLINE: This is a multicenter study. Patients are stratified according to hepatic function as defined by the Child-Pugh classification system (control [i.e., total bilirubin normal, AST/ALT normal, and PT normal, and Child-Pugh classification score of 5] vs mild impairment [Child-Pugh class A] vs moderate impairment [Child-Pugh class B] vs severe impairment [Child-Pugh class C]).

Patients receive dasatinib orally (PO) once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating dose of dasatinib 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. At least 6 patients are treated at the MTD.

Patients undergo blood sample collection on days 1 and 8 of course 1 for pharmacokinetic studies.

After completion of study treatment, patients are followed periodically for 28 days.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically confirmed solid tumor or lymphoma

    • Metastatic or unresectable disease
    • Standard curative or palliative measures do not exist or are no longer effective
    • All solid and lymphoma tumor types are eligible
    • Patients with a liver mass, elevated α-fetoprotein level (i.e., ≥ 500 ng/mL), and positive serology for viral hepatitis consistent with a diagnosis of hepatocellular carcinoma will be eligible without the need for pathologic confirmation of diagnosis
  • Measurable or nonmeasurable disease
  • Patients with brain metastases requiring corticosteroids must be on a stable or decreasing dose of corticosteroids

    • Prior brain irradiation (whole brain or gamma knife) is required for known brain metastases
    • No untreated (non-irradiated) brain metastases
  • No clinically significant pleural effusion, fluid retention, or pericardial effusion

    • Patients with a history of pleurodesis and pleural effusion (malignant or non-malignant) may be eligible but will be treated with caution
    • Patients with a history of ascites are eligible
  • Zubrod performance status 0-2
  • Life expectancy ≥ 2 months
  • Absolute neutrophil count ≥ 1,500/mm³
  • Platelets ≥ 100,000/mm³
  • Magnesium ≥ lower limit of normal (LLN)
  • Potassium ≥ LLN
  • Creatinine ≤ 1.5 times upper limit of normal OR creatinine clearance ≥ 60 mL/min
  • Patients with abnormal liver function are eligible
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Patients with biliary obstruction for which a shunt has been placed are eligible provided the liver function tests have stabilized

    • Two measurements at least 2 days apart that put the patient in the same hepatic dysfunction stratum will be accepted as evidence of stable hepatic function
    • There must be no evidence of biliary sepsis and at least 2 weeks must have elapsed after the placement of a biliary shunt
  • Must be willing to undergo pharmacokinetic sampling
  • Must be able to take oral medications
  • Patients may not have any clinically significant cardiovascular diseases including the following:

    • Myocardial infarction or ventricular tachyarrhythmia within 6 months
    • Prolonged QTc >= 480 msec (Fridericia correction)
    • Ejection fraction less than normal institutional normal
    • Major conduction abnormality (unless a cardiac pacemaker is present)
    • Patients with any cardiopulmonary symptoms of unknown cause should be evaluated by a baseline echocardiogram with or without stress test as needed in addition to EKG to rule out QTc prolongation; patients with underlying cardiopulmonary dysfunction should be excluded from the study
  • No history of allergic reaction to dasatinib or similar compounds
  • No ongoing cardiac dysrhythmias of NCI CTCAE grade ≥ 2, atrial fibrillation of any grade, or QTc interval > 470 msec for females or > 450 msec for males
  • No active gastrointestinal bleeding
  • No diagnosis of malabsorption syndrome or significant bowel resection affecting absorption
  • No clinically significant fluid retention or pericardial effusion
  • No uncontrolled serious intercurrent medical illness including, but not limited to, any of the following:

    • Ongoing or serious active infection
    • Symptomatic congestive heart failure
    • Unstable angina pectoris
    • Serious cardiac arrhythmia
    • Uncontrolled diarrhea
    • Psychiatric illness/social situation that would limit compliance with study requirements
  • No known HIV-positivity
  • Recovered from all prior therapy
  • More than 7 days since prior and no concurrent H2-receptor antagonist (e.g., cimetidine, ranitidine, or famotidine)
  • More than 7 days since prior and no concurrent proton pump inhibitors (e.g., omeprazole, lansoprazole, esomeprazole, or pantoprazole)
  • More than 4 weeks since prior major surgical procedures
  • More than 4 weeks since prior and no other concurrent or plans to receive anticancer therapy including chemotherapy, radiotherapy, immunotherapy, or investigational agents
  • At least 2 weeks since prior targeted agents with a half-life of < 24 hours
  • No prior dasatinib
  • Concurrent hormone therapy for prostate carcinoma may be continued
  • Concurrent bisphosphonate treatment for bone disease is permitted
  • No concurrent therapeutic doses of anticoagulants

    • Low dose warfarin for port prophylaxis is permitted
  • No concurrent enzyme-inducing anticonvulsant medications (e.g., phenobarbital, phenytoin, or carbamazepine)
  • No concurrent prophylactic colony-stimulating factors
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00608361

Locations
United States, Texas
Southwest Oncology Group Recruiting
San Antonio, Texas, United States, 78245
Contact: John Sarantopoulos     210-616-5798     sarantopoulo@uthscsa.edu    
Principal Investigator: John Sarantopoulos            
Sponsors and Collaborators
Investigators
Principal Investigator: John Sarantopoulos Southwest Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00608361     History of Changes
Other Study ID Numbers: NCI-2009-00792, S0711, CDR0000583976, SWOG-S0711, U10CA032102
Study First Received: January 30, 2008
Last Updated: March 26, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lymphoma, Non-Hodgkin
Burkitt Lymphoma
Carcinoma
Hodgkin Disease
Immunoblastic Lymphadenopathy
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, T-Cell
Leukemia-Lymphoma, Adult T-Cell
Liver Neoplasms
Lymphoma
Lymphoma, Follicular
Lymphoma, Large B-Cell, Diffuse
Lymphomatoid Granulomatosis
Waldenstrom Macroglobulinemia
Mycoses
Mycosis Fungoides
Sezary Syndrome
Lymphoma, B-Cell
Lymphoma, Large-Cell, Immunoblastic
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Lymphoma, T-Cell
Lymphoma, T-Cell, Cutaneous
Lymphoma, Large-Cell, Anaplastic
Lymphoma, B-Cell, Marginal Zone
Lymphoma, Extranodal NK-T-Cell
Lymphoma, Mantle-Cell
Carcinoma, Hepatocellular
Epstein-Barr Virus Infections
Herpesviridae Infections

ClinicalTrials.gov processed this record on June 18, 2013