Dasatinib in Treating Patients With Solid Tumor or Lymphoma That Are Metastatic or Cannot Be Removed By Surgery

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 these patients.

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 PK 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 multicenter study. Patients are stratified according to hepatic function
as defined by the Child-Pugh classification system (control [i.e., total bilirubin normal,
aspartate aminotransferase [AST]/alanine aminotransferase [ALT] normal, and prothrombin time
[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 (QD) 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.

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

- Patients with a liver mass, elevated alpha-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

- All solid and lymphoma tumor types are eligible

- Patients with 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 require corticosteroids must be on a stable or
decreasing dose of corticosteroids

- Patients with known brain metastases must have had prior 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 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, AST/ALT, 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

- 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