Brief Title
Dasatinib in Treating Patients With Solid Tumors or Lymphomas That Are Metastatic or Cannot Be Removed By Surgery
Official Title
Phase I Pharmacokinetic Study of Dasatinib (BMS-354825) (NSC-732517) in Patients With Advanced Malignancies and Varying Levels of Liver Dysfunction
Brief Summary
This phase I trial studies the side effects and best dose of dasatinib in treating patients
with solid tumors or lymphomas that are metastatic or cannot be removed by surgery. Dasatinib
may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Detailed Description
PRIMARY OBJECTIVES:
I. To estimate the maximum tolerated dose (MTD) of dasatinib in patients with varying degrees
of hepatic impairment.
II. To estimate the pharmacokinetic (PK) profile of this drug in patients with varying
degrees of hepatic impairment.
III. To assess the safety profile and dose-limiting toxicities (if any) of dasatinib in
patients with varying degrees of hepatic impairment.
SECONDARY OBJECTIVES:
I. To describe any antitumor efficacy associated with dasatinib administration in patients
with varying degrees of hepatic impairment.
II. To examine whether the pharmacokinetic clearance of dasatinib correlates with hepatic
function as assessed by Child-Pugh Criteria, the National Cancer Institute (NCI) Organ
Dysfunction Working Group Criteria, or other assessments of liver function.
OUTLINE: This is a dose-escalation study.
Patients receive dasatinib orally (PO) once daily (QD) on days 1-28. Courses repeat every 28
days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 28 days.
Study Phase
Phase 1
Study Type
Interventional
Primary Outcome
Maximum tolerated dose of dasatinib, defined as the highest dose level at which less than 33% of 6-9 evaluable patients experience dose-limiting toxicity
Condition
Adult Acute Lymphoblastic Leukemia in Remission
Intervention
Dasatinib
Study Arms / Comparison Groups
Treatment (dasatinib)
Description: Patients receive dasatinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
80
Start Date
October 2008
Completion Date
August 2014
Primary Completion Date
August 2014
Eligibility Criteria
Inclusion Criteria:
- Patients must have histologically or cytologically confirmed solid tumor or lymphoma
that is metastatic or unresectable and for which standard curative or palliative
measures do not exist or are no longer effective; patients with a liver mass, elevated
alpha-fetoprotein level (>= 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 the diagnosis; all solid and lymphoma tumor types
are eligible
- Patients must have measurable or non-measurable disease; x-rays and/or scans for
disease assessment must have been completed within 28 days (for measurable disease) or
42 days (for non-measurable disease) prior to registration; all disease must be
assessed and documented on the web-based Baseline Tumor Assessment Form
- Patients with brain metastases who require corticosteroids must be on stable or
decreasing dose of corticosteroids; patients with known brain metastases must have had
brain irradiation (whole brain or gamma knife); patients with untreated
(non-irradiated) brain metastases are not eligible; patients on enzyme-inducing
anticonvulsant medications (e.g. phenobarbital, phenytoin or carbamazepine) are not
eligible
- Patients must not be taking H2-receptor antagonists such as cimetidine, ranitidine,
and famotidine, or any proton pump inhibitors, such as omeprazole, lansoprazole,
esomeprazole, and pantoprazole; patients must stop these medications within 7 days
prior to starting treatment
- Patients must not have had anticancer therapy including chemotherapy, radiotherapy,
immunotherapy, or investigational agent within 4 weeks prior to registration, except
for targeted agents with half-life known to be < 24 hours; patients must not have had
targeted agents with half-life < 24 hours within 2 weeks prior to registration;
patients also must have recovered from serious adverse events due to agents
administered within these acceptable time frames
- Patients must not be planning to receive concurrent radiation, other chemotherapy,
immune therapy or any other investigational agents for malignancy while receiving
protocol treatment; hormonal treatment for prostate carcinoma may be continued and
bisphosphonate treatment for bone disease is permitted
- Patient must not have received prior therapy with dasatinib (BMS-354825)
- Patients for whom there is a strong suspicion of being allergic to dasatinib because
of a history of allergic reactions to similar compounds are not eligible
- Patients must not have had major surgical procedures within the last 4 weeks prior to
the first planned dose of study drug
- Patients must not be taking therapeutic doses of anticoagulants; low dose warfarin for
port prophylaxis is permitted
- Zubrod performance status of 0-2
- Patients may not have any clinically significant cardiovascular disease including the
following:
- Myocardial infarction or ventricular tachyarrhythmia within 6 months
- Prolonged corrected QT interval (QTc) >= 480 msec (Fridericia correction)
- Ejection fraction less than institutional normal
- Major conduction abnormality (unless a cardiac pacemaker is present)
- Patients with any cardiopulmonary symptoms of unknown cause (e.g. shortness of
breath, chest pain, etc.) should be evaluated by a baseline echocardiogram with
or without stress test as needed in addition to electrocardiogram (EKG) to rule
out QTc prolongation; the patient may be referred to a cardiologist at the
discretion of the principal investigator; patients with underlying
cardiopulmonary dysfunction should be excluded from the study
- Absolute neutrophil count >= 1.5 x 10^9/L
- Platelets >= 100 x 10^9/L
- Magnesium >= lower limit of normal (LLN)
- Potassium >= LLN
- Creatinine =< 1.5 x upper limit of normal (ULN) OR calculated creatinine clearance >=
60 mL/min/1.73 m^2; if less than the normal range, supplementation should be initiated
in the manner deemed appropriate by the treating physician
- Patients with abnormal liver function are eligible and will be grouped according to
the criteria; no distinction will be made between liver dysfunction due to metastases
and liver dysfunction due to other causes; for patient registration, liver function
tests (total bilirubin, aspartate aminotransferase [AST]/alanine aminotransferase
[ALT], prothrombin time [PT]/international normalized ratio [INR] and partial
thromboplastin time [PTT], and alkaline phosphatase) must be performed within 14 days
prior to registration; for patient stratification, liver function tests must be
performed within 72 hours of anticipated starting time of protocol treatment; patients
must be stratified and treated based on the liver function tests performed within 72
hours prior to treatment; the South West Oncology Group (SWOG) Data Operations Center
must be notified in writing in cases where the patient's cycle 1 pre-treatment liver
function tests result in stratification to a dysfunction group different from how the
patient was classified at registration
- Patients with biliary obstruction for which a shunt has been placed are eligible,
provided the liver function tests have stabilized (two measurements at least two 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
- Patients must not be pregnant or nursing; women/men of reproductive potential must
have agreed to use an effective contraceptive method; since interaction with dasatinib
and oral contraceptives is possible, a barrier method should be used and oral
contraceptives are not permitted; a negative pregnancy test is required within 72
hours prior to starting therapy for women of reproductive potential; a woman is
considered to be of "reproductive potential" if she has had menses at any time in the
preceding 12 consecutive months; in addition to routine contraceptive methods,
"effective contraception" also includes heterosexual celibacy and surgery intended to
prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a
hysterectomy, bilateral oophorectomy or bilateral tubal ligation; however, if at any
point a previously celibate patient chooses to become heterosexually active during the
time period for use of contraceptive measures outlined in the protocol, he/she is
responsible for beginning contraceptive measures
- Patients who have experienced any of the following within the 12 months prior to
starting protocol treatment are not eligible: myocardial infarction, severe/unstable
angina, coronary/peripheral artery bypass graft, congestive heart failure,
cerebrovascular accident including transient ischemic attack, or significant pulmonary
embolus
- Patients with ongoing cardiac dysrhythmias of NCI Common Terminology Criteria for
Adverse Events (CTCAE) grade >= 2, atrial fibrillation of any grade, or QTc interval >
470 msec for females or > 450 msec for males are not eligible
- Patients with baseline pleural effusion are not eligible
- Patients must not have active gastrointestinal bleeding
- Patients with the inability to take oral medications, with a diagnosis of
malabsorption syndromes or with significant bowel resection affecting absorption are
not eligible
- Patients with a clinically significant pleural effusion/ fluid retention/pericardial
effusion are not eligible; patients with a history of pleurodesis and previous pleural
effusion (malignant or non-malignant) may be eligible but treated with caution;
patients with previous history of ascites may be treated
- Patients with uncontrolled serious intercurrent medical illness including, but not
limited to ongoing or serious active infection, symptomatic congestive heart failure,
unstable angina pectoris, serious cardiac arrhythmia, uncontrolled diarrhea or
psychiatric illness/social situations that would limit compliance with study
requirements are not eligible
- Patients known to be human immunodeficiency virus (HIV)-positive are not eligible;
however, patients will not routinely be screened for HIV
- Patients must be willing to undergo pharmacokinetic sampling
- Patients or their legally authorized representative must be informed of the
investigational nature of this study and must sign and give written informed consent
in accordance with institutional and federal guidelines
- At the time of patient registration, the treating institution's name and
identification (ID) number must be provided to the Statistical Center in order to
ensure that the current (within 365 days) date of institutional review board approval
for this study has been entered into the data base
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
John Sarantopoulos, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT00608361
Organization ID
NCI-2009-00792
Secondary IDs
NCI-2009-00792
Responsible Party
Sponsor
Study Sponsor
National Cancer Institute (NCI)
Study Sponsor
John Sarantopoulos, Principal Investigator, Southwest Oncology Group
Verification Date
June 2015