Phase II Studies of Two Different Schedules of Dasatinib (NSC-732517) in Bone Metastasis Predominant Metastatic Breast Cancer

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Diagnosis of breast carcinoma meeting the following criteria:

- Stage IV disease

- Bone metastasis-predominant disease, defined as the presence of ≥ 1 bone
metastasis with or without nonbone (visceral or soft tissue) disease where the
number of bone metastases is at least the number of measurable visceral target
lesions

- Visceral disease that does not cause a reduction in ECOG performance status
allowed

- Must meet 1 of the following criteria:

- Measurable disease within the past 28 days

- Nonmeasurable disease with rising serum CA 15-3, CA 27-29, CEA, or CA-125
documented by 2 consecutive measurements taken ≥ 14 days apart with the most
recent measurement being within the past 42 days

- These measurements need not be consecutive, and the prior measurement could
have been months to years prior to the current measurement if the marker is
considered by the investigator to reflect disease progression

- The second serum marker value must be greater than the institution's upper
limit of normal and show ≥ a 20% increase over the first measurement

- No symptomatic brain or CNS metastases

- Prior CNS or brain metastasis allowed provided it was treated with radiotherapy
≥ 8 weeks ago

- No pleural or pericardial effusion

- Hormone receptor status known

- Estrogen receptor- and/or progesterone receptor-positive disease must have
progressed on ≥ 1 hormonal therapy in the metastatic setting

PATIENT CHARACTERISTICS:

- Male or female

- Menopausal status not specified

- Zubrod performance status 0-2

- QTc < 450 msec by EKG

- Ejection fraction ≥ 50% by MUGA or 2-dimensional echocardiogram with no significant
abnormalities within the past 12 weeks for patients on trastuzumab

- No active infection requiring systemic therapy

- No uncontrolled concurrent condition that would preclude the ability to take oral
medication, including the following:

- Nausea

- Vomiting

- Diarrhea

- Lack of physical integrity of the upper gastrointestinal tract

- Malabsorption syndrome

- No clinically significant cardiac disease, including the following:

- Congestive heart failure

- Symptomatic coronary artery disease

- Cardiac arrhythmias not well controlled

- Myocardial infarction within the past 12 months

- No concurrent active malignancy

- Prior malignancies allowed provided the patient is currently disease-free

- Not pregnant or nursing

- Fertile patients must use effective contraception during and for 3 months after
completion of study therapy

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- No prior RankL inhibitor therapy

- No more than 1 prior cytotoxic chemotherapy for metastatic disease

- At least 3 weeks since prior chemotherapy and recovered

- At least 1 week since prior radiotherapy to non-CNS disease and recovered

- At least 3 weeks since prior and no concurrent intravenous bisphosphates (e.g.,
zoledronate)

- At least 7 days since prior and no concurrent antiplatelet agents, including any of
the following*:

- Anticoagulants (e.g., tirofiban, eptifibatide, ticlopidine)

- Aspirin or aspirin-containing combinations

- Dipyridamole

- Epoprostenol

- Clopidogrel

- Cilostazol

- Abciximab NOTE: *Nonsteroidal anti-inflammatory drugs and medically indicated
platelet-inhibiting medication allowed

- At least 7 days since prior and no concurrent CYP3A4 inhibitors, including any of the
following:

- HIV protease inhibitors (e.g., amprenavir, atazanavir, fosamprenavir, indinavir,
nelfinavir, ritonavir)

- Select antibiotics (e.g., ciprofloxacin, clarithromycin, doxycycline, enoxacin,
isoniazid, telithromycin)

- Azole antifungals (e.g., itraconazole, ketoconazole, miconazole, voriconazole)

- Select anesthetics (e.g., ketamine, propofol)

- Hypericum perforatum (St. John's wort)

- Nefazodone

- Nicardipine

- Diclofenac

- Quinidine

- Imatinib mesylate

- At least 7 days since prior and no concurrent medications that prolong the QTc
interval, including any of the following:

- Antiarrhythmic agents (e.g., quinidine, procainamide, disopyramide phosphate,
amiodarone, sotalol hydrochloride, ibutilide, dofetilide)

- Antipsychotic agents (e.g., chlorpromazine, mesoridazine, thioridazine,
pimozide, haloperidol, droperidol)

- Select antibiotics (e.g., erythromycin, clarithromycin, sparfloxacin,
pentamidine)

- Narcotic analgesics (e.g., levomethadyl, methadone, domperidone)

- Calcium channel blockers (e.g., bepridil, lidoflazine)

- Antimalarial agents (e.g., halofantrine, chloroquine)

- Parasympathomimetic agents (e.g., cisapride)

- Arsenic trioxide

- No other concurrent antineoplastic therapy for breast cancer, including any of the
following:

- Radiotherapy

- Chemotherapy

- Immunotherapy

- Biologic therapy

- Hormonal therapy

- Gene therapy

- No concurrent grapefruit juice consumption

- No concurrent short-acting antacid agents within 2 hours of dasatinib administration

- Concurrent trastuzumab (Herceptin®) therapy for HER-2 positive patients allowed
provided patients have been on continuous trastuzumab for ≥ 12 weeks