S0622, Dasatinib in Treating Patients With Stage IV Breast Cancer That Has Spread to the Bone
Condition: Breast Cancer; Metastatic Cancer
MeSH terms: Breast Neoplasms
Intervention: dasatinib
Intervention description: given orally
Intervention MeSH terms: Dasatinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 85.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: stage IV breast cancer; male breast cancer; recurrent breast cancer; bone metastases

Summary:

      RATIONALE: Dasatinib may stop the growth of tumor cells by blocking some of the enzymes
      needed for cell growth.

      PURPOSE: This randomized phase II trial is studying two different schedules of dasatinib to
      compare how well they work in treating patients with stage IV breast cancer that has spread
      to the bone.
    

Eligibility 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