A Phase II Evaluation of Dasatinib (Sprycel®, NSC #732517) in the Treatment of Persistent or Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Carcinoma
Condition: Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma
MeSH terms: Carcinoma; Recurrence
Intervention: Dasatinib; Laboratory Biomarker Analysis
Intervention description: Given orally; Correlative studies
Intervention MeSH terms: Dasatinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 35.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Dasatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell
      growth. This phase II trial is studying how well dasatinib works in treating patients with
      persistent or recurrent ovarian epithelial cancer, fallopian tube cancer, or primary
      peritoneal cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have recurrent or persistent epithelial ovarian, fallopian tube, or
             primary peritoneal carcinoma; histologic documentation of the original primary tumor
             is required via the pathology report

          -  All patients must have measurable disease; measurable disease is defined as at least
             one lesion that can be accurately measured in at least one dimension (longest
             dimension to be recorded); each lesion must be >= 20 mm when measured by conventional
             techniques, including palpation, plain x-ray, CT, and MRI, or >= 10 mm when measured
             by spiral CT

          -  Patients must have at least one "target lesion" to be used to assess response on this
             protocol as defined by RECIST; tumors within a previously irradiated field will be
             designated as "non-target" lesions unless progression is documented or a biopsy is
             obtained to confirm persistence at least 90 days following completion of radiation
             therapy

          -  Patients must not be eligible for a higher priority GOG protocol, if one exists; in
             general, this would refer to any active GOG Phase III protocol for the same patient
             population

          -  Patients who have received one prior regimen must have a GOG Performance Status of 0,
             1, or 2; patients who have received two prior regimens must have a GOG Performance
             Status of 0 or 1

          -  Recovery from effects of recent surgery, radiotherapy, or chemotherapy

               -  Patients should be free of active infection requiring antibiotics (with the
                  exception of uncomplicated UTI).

               -  Any hormonal therapy directed at the malignant tumor must be discontinued at
                  least one week prior to registration; continuation of hormone replacement therapy
                  is permitted

               -  Any other prior therapy directed at the malignant tumor, including immunologic
                  agents, must be discontinued at least three weeks prior to registration; six
                  weeks for patient previously treated with monoclonal antibodies

          -  Prior therapy

               -  Patients must have had one prior platinum-based chemotherapeutic regimen for
                  management of primary disease containing carboplatin, cisplatin, or another
                  organoplatinum compound; this initial treatment may have included intraperitoneal
                  therapy, high-dose therapy, consolidation, non-cytotoxic agents or extended
                  therapy administered after surgical or non-surgical assessment

               -  Patients are allowed to receive, but are not required to receive, one additional
                  cytotoxic regimen for management of recurrent or persistent disease according to
                  the following definition:

                    -  Cytotoxic regimens include any agent that targets the genetic and/or mitotic
                       apparatus of dividing cells, resulting in dose-limiting toxicity to the bone
                       marrow and/or gastrointestinal mucosa

                    -  Note: patients on this non-cytotoxic study are allowed to receive additional
                       cytotoxic chemotherapy for management of recurrent or persistent disease, as
                       defined above

               -  Patients must have NOT received any non-cytotoxic therapy for management of
                  recurrent or persistent disease; patients are allowed to receive, but are not
                  required to receive, biologic (non-cytotoxic) therapy as part of their primary
                  treatment regimen

               -  Patients who have received only one prior cytotoxic regimen (platinum-based
                  regimen for management of primary disease), must have a platinum-free interval of
                  less than 12 months, or have progressed during platinum-based therapy, or have
                  persistent disease after a platinum-based therapy

          -  Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl, equivalent to
             CTCAE v 3.0 grade 1

          -  Platelets greater than or equal to 100,000/mcl

          -  Hemoglobin greater than or equal to 10 g/dL

          -  Creatinine less than or equal to 1.5 x institutional upper limit normal (ULN), CTCAE
             v3.0 grade 1

          -  Bilirubin less than or equal to 1.5 x ULN, CTCAE v3.0 grade 1

          -  SGOT and alkaline phosphatase less than or equal to 2.5 x ULN, CTCAE v3.0 grade 1

          -  Mg++, CA++, phosphate, K+, Na corrected to WNL

          -  PT/INR, PTT less than or equal to 1 - 1.5 x ULN, CTCAE v 3.0 grade 1 except for
             patients on therapeutic anticoagulation

          -  Neuropathy (sensory and motor) less than or equal to CTCAE v 3.0 grade 1

          -  QTc interval on electrocardiogram must be less than or equal to 450 msec

          -  Patients must have signed an approved informed consent and authorization permitting
             release of personal health information

          -  Patients must meet pre-entry requirements as specified in section 7.0

          -  Patients of childbearing potential must have a negative serum pregnancy test within 72
             hours prior to initiating protocol therapy and be practicing an effective form of
             contraception during protocol therapy and for at least 4 weeks following completion of
             protocol therapy

          -  Patients must not be receiving any other investigational agent

          -  Patients must be able to swallow whole pills

        Exclusion Criteria:

          -  Patients who have had previous treatment with dasatinib

          -  Patients who have received radiation to more than 25% of marrow-bearing areas

          -  Patients with a history of other invasive malignancies, with the exception of
             non-melanoma skin cancer and other specific malignancies are excluded if there is any
             evidence of other malignancy being present within the last five years; patients are
             also excluded if their previous cancer treatment contraindicates this protocol therapy

          -  Patients who have received prior radiotherapy to any portion of the abdominal cavity
             or pelvis OTHER THAN for the treatment of ovarian, fallopian tube, or primary
             peritoneal cancer within the last five years are excluded; prior radiation for
             localized cancer of the breast, head and neck, or skin is permitted, provided that it
             was completed more than three years prior to registration, and the patient remains
             free of recurrent or metastatic disease

          -  Patients cannot take St. John's Wort or drink grapefruit juice while on study
             treatment (discontinue St. John's Wort at least five days before starting dasatinib)

          -  Patients receiving IV bisphosphonates agree that IV bisphosphonates will be withheld
             for the first 8 weeks of dasatinib therapy due to risk of hypocalcemia, and may be
             restarted only if any hypocalcemia has been corrected

          -  Patients who have a history of cardiac disease:

               -  Uncontrolled angina, congestive heart failure (CHF) or myocardial infarction (MI)
                  within six months prior to study entry;

               -  Diagnosed congenital long QT syndrome;

               -  Clinically significant ventricular arrhythmias (such as ventricular tachycardia
                  [VT], ventricular fibrillation [VF], or Torsades de pointes)

          -  Patients with hypokalemia or hypomagnesemia if it cannot be corrected to within normal
             limits prior to dasatinib treatment

          -  Patients who have a history of significant bleeding disorder unrelated to cancer
             including:

               -  Bleeding diathesis, congenital or acquired within one year prior to initiating
                  protocol therapy (e.g., von Willebrand's disease, acquired anti-factor VIII
                  antibodies);

               -  Significant GI bleeding within three months prior to initiating protocol therapy

          -  Dasatinib is metabolized primarily by the CYP3A4 liver enzyme; consideration should be
             given to using alternative medications not impacting CYP3A4 while on dasatinib therapy

               -  Patients may not be receiving any prohibited potent CYP3A4 inhibitors; for these
                  drugs, a wash-out period of >= 7 days is required prior to starting dasatinib
                  treatment

          -  Category I drugs that are generally accepted to have a risk of causing Torsades de
             Pointes; a wash-out period of >= 7 days is required for the following drugs prior to
             starting dasatinib treatment:

               -  Quinidine, procainamide, disopyramide

               -  Amiodarone, sotalol, ibutilide, dofetilide

               -  Erythromycin, clarithromycin

               -  Chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide

               -  Cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone,
                  halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine

          -  The concomitant use of H2 blockers and proton pump inhibitors (PPIs) with dasatinib is
             not recommended (e.g., famotidine, omeprazole); the use of antacids should be
             considered in place of H2 blockers or proton pump inhibitors in patients receiving
             dasatinib therapy; if antacid therapy is needed, the antacid dose should be
             administered two hours before or after the dose of dasatinib

          -  Therapeutic anticoagulation is not contraindicated, but for those patients on
             therapeutic anticoagulation, alteration in coagulation parameters is expected
             following initiation of dasatinib. For patients on therapeutic anticoagulation,
             coagulation parameters should be assessed weekly for the first cycle following
             initiation of dasatinib, weekly for the first cycle following a dose reduction, and
             weekly for a minimum of two weeks after stopping dasatinib.

        Warfarin is permitted for prophylaxis or treatment of thrombosis

          -  Note: Low molecular weight heparin is permitted provided the patient's PT/INR is =<
             1.5; for patients on anticoagulation, coagulation parameters should be assessed weekly
             for the first cycle following initiation of dasatinib, weekly for the first cycle
             following a dose reduction, and weekly for a minimum of two weeks after stopping
             dasatinib

               -  Pregnant or nursing women; women of childbearing potential unless using effective
                  contraception as determined by the investigator