Sunitinib Malate in Treating Patients With Recurrent Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cancer
Condition: Recurrent Fallopian Tube Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Primary Peritoneal Cavity Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Primary Peritoneal Cavity Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Primary Peritoneal Cavity Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Primary Peritoneal Cavity Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Primary Peritoneal Cavity Cancer
MeSH terms: Fallopian Tube Neoplasms; Carcinoma, Ovarian Epithelial; Peritoneal Neoplasms; Recurrence
Intervention: sunitinib malate; laboratory biomarker analysis
Intervention description: Given PO; Correlative studies
Intervention MeSH terms: Sunitinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 31.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies the side effects and how well sunitinib malate works in treating
      patients with recurrent ovarian epithelial, fallopian tube, or primary peritoneal cancer.
      Sunitinib malate may inhibit the ability of cancers to grow blood vessels, something they
      need to grow. It may also shrink tumors.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically confirmed epithelial ovarian, primary fallopian or
             primary peritoneal cancer

          -  Patients must have advanced and/or metastatic disease, incurable by standard therapies

          -  Patients must have received one or two prior chemotherapy regimens (one must have been
             platinum containing) and may be either platinum sensitive or platinum resistant

               -  Nota bene (NB): For the purposes of this trial, switching from one platinum
                  compound to another for reasons of disease progression or failure to respond will
                  be considered a second regimen; as well, the same regimen given as first and
                  second-line therapy is also considered two regimens

          -  Presence of clinically and/or radiologically documented disease; at least one site of
             disease must be unidimensionally measurable as follows:

               -  X-ray, physical exam >= 20 mm

               -  Spiral computed tomography (CT) scan >= 10 mm; N.B.: Most Canadian hospitals have
                  spiral CT scanning equipment

               -  Non-spiral CT scan >= 20 mm; N.B.: Most Canadian hospitals have spiral CT
                  scanning equipment

                    -  All radiology studies must be performed within 21 days prior to registration
                       (within 28 days if negative)

                    -  Patients with CA125 as only evidence of disease are not eligible

          -  Patients must have a life expectancy of at least 12 weeks

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

          -  Hormonal therapy: Patients may have had up to one prior hormonal treatment for
             metastatic disease; patients must be at least 28 days since last dose of hormonal
             therapy

          -  Chemotherapy: Patients must have had a minimum of one and up to two prior chemotherapy
             regimens, one of which must have contained a platinum agent; patients must be at least
             28 days since last chemotherapy treatment and must have recovered from toxic effects

          -  Radiation: Patients may have had prior radiation therapy; a minimum of 28 days must
             have elapsed between the end of radiotherapy and registration onto the study;
             radiation must have involved < 30% of functioning bone marrow and there must be
             measurable disease outside the previously irradiated area (patients whose sole site of
             disease is in a previously irradiated area are ineligible UNLESS there is evidence of
             progression, or new lesions have been documented, in the irradiated field);
             (exceptions may be made however, for low dose, palliative radiotherapy); patients must
             have recovered from any acute toxic effects from radiation prior to registration

          -  Previous surgery: Previous major surgery is permitted provided that it has been at
             least 28 days prior to patient registration and that wound healing has occurred

          -  Granulocytes (absolute granulocyte count [AGC]) >= 1.5 x 10^9/L

          -  Platelets >= 100 x 10^9/L

          -  Bilirubin =< upper limit of normal (ULN)

          -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN

          -  Calcium =< 3 mmol/L

          -  Serum creatinine =< ULN or creatinine clearance >= 60 ml/min if creatinine is > ULN

               -  Creatinine clearance to be measured directly by 24 hour urine sampling or as
                  calculated by Cockcroft formula

          -  Patient consent must be obtained according to local Institutional and/or University
             Human Experimentation Committee requirements; it will be the responsibility of the
             local participating investigators to obtain the necessary local clearance, and to
             indicate in writing to the National Cancer Institute of Canada (NCIC) Clinical Trials
             Group (CTG) study coordinator that such clearance has been obtained, before the trial
             can commence in that center; a standard consent form for the trial will not be
             provided; a copy of the initial full board Research Ethics Board (REB) approval and
             approved consent form must be sent to the central office; the patient must sign the
             consent form prior to randomization or registration; please note that the consent form
             for this study must contain a statement which gives permission for the NCIC CTG and
             monitoring agencies to review patient records

          -  Patients must be accessible for treatment, response assessment and follow-up; patients
             registered on this trial must be treated and followed at the participating center;
             this implies there must be reasonable geographical limits (for example: 1 ½ hour's
             driving distance) placed on patients being considered for this trial; investigators
             must assure themselves the patients registered on this trial will be available for
             complete documentation of the treatment, adverse events, and follow-up

          -  In accordance with NCIC CTG policy, protocol treatment is to begin within 2 working
             days of patient registration; exceptions may be made however, regarding the washout
             period timing for prohibited medications

        Exclusion Criteria:

          -  History of other malignancies, except: adequately treated non-melanoma skin cancer,
             curatively treated in-situ cancer of the cervix, or other solid tumors curatively
             treated with no evidence of disease for >= 5 years

          -  Patients with known brain metastases; (a head CT is not necessary to rule out brain
             metastases, unless there is clinical suspicion of central nervous system [CNS]
             involvement); patients with known brain metastases will be excluded from this trial

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to sunitinib

          -  Patients receiving concurrent treatment with other anti-cancer therapy or other
             investigational anticancer agents

          -  Patients who have received prior treatment with any other antiangiogenic agent or
             multi-targeted tyrosine kinase inhibitors (e.g. bevacizumab, sorafenib, pazopanib,
             thalidomide, AZD6474, AMG-706, AZD2171, PTK787, vascular endothelial growth factor
             [VEGF] Trap, etc.) are ineligible

          -  Patients with any of the following cardiovascular findings are to be excluded:

               -  Corrected QT interval (QTc) prolongation (defined as a QTc interval equal to or
                  greater than 500 msec) or other significant electrocardiogram (ECG)
                  abnormalities; an ECG must be done within 14 days prior to registration

               -  Current or history of class III or IV heart failure as defined by the New York
                  Heart Association (NYHA) functional classification system

               -  Patients with prior anthracycline exposure, previous central thoracic radiation
                  that included heart in radiation port, or a history of NYHA class II cardiac
                  function UNLESS

                    -  They are currently asymptomatic with respect to cardiac function AND

                    -  Left ventricular ejection fraction (LVEF) as assessed by multi gated
                       acquisition scan (MUGA) at baseline is > lower limit of normal (LLN) of
                       institution; the MUGA must be done within 14 days prior to registration

               -  Poorly controlled hypertension (systolic blood pressure of 140 mmHg or higher or
                  diastolic blood pressure of 90 mmHg or higher)

               -  Myocardial infarction, cardiac arrhythmia, stable/unstable angina, symptomatic
                  congestive heart failure, or coronary/peripheral artery bypass graft or stenting
                  within 12 months prior to study entry

               -  History of pulmonary embolism within the past 12 months

               -  History of cerebrovascular accident (CVA) or transient ischemic attack within 12
                  months prior to study entry

          -  Patients who require use of therapeutic doses of coumarin-derivative anticoagulants
             such as warfarin are excluded, although doses of up to 2 mg daily are permitted for
             prophylaxis of thrombosis; Note: Low molecular weight heparin is permitted provided
             the patient's international normalized ratio (INR) is =< 1.5; INR must be done within
             7 days prior to registration

          -  Patients with bowel obstruction or any condition (e.g. gastrointestinal tract disease
             resulting in an inability to take oral medication or a requirement for intravenous
             (IV) alimentation, prior surgical procedures affecting absorption, or active peptic
             ulcer disease) that impairs their ability to swallow and retain sunitinib tablets

          -  Patients with serious illness or medical condition which would not permit the patient
             to be managed according to the protocol including, but not limited to:

               -  History of significant neurologic or psychiatric disorder which would impair the
                  ability to obtain consent or limit compliance with study requirements

               -  Active uncontrolled infection

               -  Any other medical conditions that might be aggravated by treatment

               -  Serious or non-healing wound, ulcer, or bone fracture

               -  Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess
                  within 28 days of treatment

          -  Use of agents with proarrhythmic potential (terfenadine, quinidine, procainamide,
             disopyramide, sotalol, probucol, bepridil, haloperidol, risperidone, indapamide and
             flecainide) is not permitted during the study

          -  The concomitant use of certain drugs is prohibited; patients receiving List A drugs
             below are not eligible unless >= 7 days since last dose before starting sunitinib and
             no dosing during the trial; patients receiving List B drugs below are not eligible
             unless >= 12 days since last dose before starting sunitinib and no dosing during the
             trial

               -  List A: inhibitor/substrates - prohibited 7 days before dosing and during study

                    -  Azole antifungals (ketoconazole, itraconazole, miconazole), verapamil,
                       clarithromycin, human immunodeficiency virus (HIV) protease inhibitors
                       (indinavir, saquinavir, ritonavir, atazanavir, nelfinavir), erythromycin,
                       delavirdine, diltiazem

               -  List B: inducer/substrates - prohibited 12 days before dosing and during study

                    -  Rifampin, phenytoin, rifabutin, St. John's wort, carbamazepine, efavirenz,
                       phenobarbital, tipranavir

          -  Patients with pre-existing hypothyroidism prior to enrollment are ineligible unless
             they are euthyroid on medication

          -  Most women enrolled on this study will have had a prior hysterectomy for ovarian
             cancer; however, the following are exclusions for enrolment on the study:

               -  Pregnant or lactating women; (N.B.: all women of childbearing potential must have
                  a negative urine beta-human chorionic gonadotropin (b-HCG) pregnancy test within
                  7 days prior to registration)

               -  Women of childbearing potential who do not agree to use adequate contraception
                  (hormonal or barrier method of birth control; abstinence) prior to study entry
                  and for the duration of study participation; (should a woman become pregnant or
                  suspect she is pregnant while participating in this study, she should inform her
                  treating physician immediately)

          -  Known HIV-positive patients on combination antiretroviral therapy are ineligible