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Phase I Pharmacokinetic Study of Dasatinib (BMS-354825) (NSC-732517; IND-73969) in Patients With Advanced Malignancies and Varying Levels of Liver Dysfunction
| City: |
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San Antonio |
| State: |
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Texas |
| Zip Code: |
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78245 |
| Conditions: |
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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 Margin |
| Purpose: |
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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.
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| Study Summary: |
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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.
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| Criteria: |
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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
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| NCT ID: |
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NCT00608361 |
| Primary Contact: |
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Principal Investigator
John Sarantopoulos
Southwest Oncology Group
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| Backup Contact: |
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N/A |
| Location Contact: |
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San Antonio, Texas 78245
United States
John Sarantopoulos
Phone: 210-616-5798
Email: sarantopoulo@uthscsa.edu
Site Status: Recruiting |
| Data Source: |
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ClinicalTrials.gov |
| Date Processed: |
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May 22, 2013 |
| Modifications to this listing: |
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