Sunitinib for Advanced Thymus Cancer Following Earlier Treatment
Condition: Thymoma; Thymus Neoplasms
MeSH terms: Thymoma; Thymus Neoplasms
Intervention: Sunitinib; Sunitinib
Intervention description: 50mg/day for 4 weeks daily, by mouth with 2 weeks off (6 week cycle); 50mg/day for 2 weeks daily, by mouth with 1 week off (3 week cycle)
Intervention MeSH terms: Sunitinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 56.0
Sex: All
Minimum age: 18 Years
Maximum age: 100 Years
Healthy volunteers: No
Keywords: VEGF; Anti-Angiogenesis; Targeted Agent

Summary:

      Background:

      - Sunitinib is drug that is approved for treating various types of cancers, including kidney
      cancers. However, it has not been approved to treat cancers of the thymus. Sunitinib works by
      blocking proteins that are responsible for cell division and growth. Some of these proteins
      can be found on thymus cancer cells. Researchers want to see if sunitinib can be used to
      treat advanced thymus cancer. It will be given to people who have had at least one earlier
      chemotherapy treatment containing platinum.

      Objectives:

      - To see if sunitinib is a safe and effective treatment for advanced thymus cancer that has
      not responded to earlier treatments.

      Eligibility:

        -  Individuals at least 18 years of age who have advanced thymus cancer that has not
           responded to earlier treatments.

        -  At least one previous cancer treatment must have been chemotherapy treatment containing
           platinum.

      Design:

        -  Participants will be screened with a physical exam and medical history. Blood and urine
           samples will be collected. Imaging studies and tumor biopsies will be used to check the
           severity of the cancer.

        -  Participants will take sunitinib tablets once a day, in the morning. They will take the
           tablets daily for 4 weeks, followed by 2 weeks of rest with no sunitinib. This 6-week
           period is called a cycle.

        -  Treatment will be monitored with frequent blood tests and imaging studies.

        -  Treatment cycles may be repeated as long as the tumor does not continue to grow and
           there are no severe side effects....
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

        3.1.1 Histological confirmation of thymoma (Group 1 only) or thymic carcinoma by the
        pathology department/Center for Cancer Research (CCR)/national Cancer Institute (NCI) or
        the pathology department of participating institutions.

        3.1.2 At least one prior line of platinum-based chemotherapy or patient must have refused
        cytotoxic chemotherapy. Progressive disease must be documented prior to study entry.

        3.1.3 Patients must not have received chemotherapy, radiation therapy, or undergone major
        surgery within 4 weeks prior to enrollment.

        3.1.4 Patients must have measurable disease, per Response Evaluation Criteria in Solid
        Tumors (RECIST) 1.1

        3.1.5 Age greater than or equal to 18 years.

        3.1.6 Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2
        (Karnofsky > 50 percent)

        3.1.7 Life expectancy of greater than 3 months.

        3.1.8 Patients must have normal organ and marrow function as defined below:

          -  hemoglobin greater than or equal to 9 g/dL

          -  leukocytes greater than or equal to 3,000/mcL

          -  absolute neutrophil count greater than or equal to 1,200/mcL

          -  platelets greater than or equal to 100,000/mcL

          -  total bilirubin within normal institutional limits

          -  serum calcium less than or equal to 12.0 mg/dL

          -  Aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase
             (SGOT)/alanine transaminase (ALT)/serum glutamic-pyruvic transaminase (SGPT) less than
             or equal to 2.5 times institutional upper limit of normal

          -  creatinine within normal institutional limits

        OR

          -  creatinine clearance greater than or equal to 60 mL/min/1.73 m(2) for patients with
             creatinine levels above institutional normal.

          -  If subjects have liver metastases, both ALT and AST must be less than or equal to 5
             times upper limit of normal (ULN).

          -  Patients must have corrected QT Interval (QTc) < 500 msec

        3.1.9 Prothrombin time (PT) or international normalized ratio (INR), and partial
        thromboplastin time test (APTT) less than or equal to 1.5 times upper limit of normal
        (ULN), unless the abnormality can be explained by the presence of lupus anticoagulant or if
        these values are in the therapeutic range for a patient on low molecular weight heparin.

        3.1.10 The following groups of patients are eligible provided they have New York Heart
        Association Class II (NYHA) cardiac function on baseline echocardiogram (ECHO)/multi-gated
        acquisition scan (MUGA):

          -  those with a history of Class II heart failure who are asymptomatic on treatment

          -  those with prior anthracycline exposure

          -  those who have received central thoracic radiation that included the heart in the
             radiotherapy port.

        3.1.11 Patients must have blood pressure (BP) no greater than 140 mmHg (systolic) and 90
        mmHg (diastolic) for eligibility. Initiation or adjustment of BP medication is permitted
        prior to study entry provided that the average of three BP readings at a visit prior to
        enrollment is less than 140/90 mmHg.

        3.1.12 Absence of brain metastases as confirmed by imaging of the brain by magnetic
        resonance imaging (MRI) or computed tomography (CT) brain with contrast performed at
        baseline screening

        3.1.13 The effects of sunitinib on the developing human fetus at the recommended
        therapeutic dose are unknown. For this reason and because anti-angiogenic agents are known
        to be teratogenic, women of childbearing potential and men must agree to use adequate
        contraception (hormonal or barrier method of birth control; abstinence) prior to study
        entry and for the duration of study participation. All women of childbearing potential must
        have a negative pregnancy test prior to receiving sunitinib. Should a woman become pregnant
        or suspect she is pregnant while participating in this study, she should inform her
        treating physician immediately. Men treated or enrolled on this protocol must also agree to
        use adequate contraception prior to the study, for the duration of study participation, and
        4 months after completion of sunitinib administration.

        3.1.14 Ability to understand and willingness to sign a written informed consent document.

        EXCLUSION CRITERIA:

        3.2.1 Patients with tumor amenable to potentially curative therapy.

        3.2.2 Prior treatment within the past 6 months with sunitinib, sorafenib, bevacizumab or
        other multikinase inhibitors targeting any of the following: vascular endothelial growth
        factors 1 3 (VEGF1 3), FMS-like tyrosine kinase 3 (FLT3), stem cell growth factor (c-KIT),
        platelet-derived growth factors-alpha and -beta (PDGF-alpha,-beta), colony-stimulating
        factor 1 (CSF1), and the RET receptor for glial-derived neurotrophic factors.

        3.2.3 Patients with symptomatic brain metastases will be excluded from trial secondary to
        poor prognosis. However, patients who have had treatment for their brain metastasis and
        whose brain disease has remained stable for 3 months without steroid therapy may be
        enrolled.

        3.2.4 Patients with evidence of severe or uncontrolled systemic disease, or any concurrent
        condition, which could compromise participation in the study, including, but not limited
        to, active or uncontrolled infection, immune deficiencies, uncontrolled hepatitis B virus
        (HBV) and/or hepatitis C virus (HCV) infection unless sustained virologic response to HCV
        therapy, uncontrolled diabetes, serious non-healing ulcer, wound or bone fracture, history
        of intra-abdominal abscess, abdominal fistula or gastrointestinal perforation within 28
        days of treatment, history of pulmonary embolism in the past 12 months, uncontrolled
        hypertension, 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, Class III or IV heart failure as defined by
        the NYHA functional classification system, stroke/cerebrovascular accident or transient
        ischemic attack within the past 12 months or psychiatric illness/social situations which
        would jeopardize compliance with the protocol.

        3.2.5 History of a previous invasive malignancy within the last 5 years, except adequately
        treated non-melanoma skin cancer, papillary carcinoma of the thyroid or carcinoma in situ
        of the uterine cervix.

        3.2.6 Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
        nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered
        from adverse events due to agents administered more than 4 weeks earlier.

        3.2.7 Patients who are receiving any other investigational agents.

        3.2.8 History of allergic reactions attributed to compounds of similar chemical or biologic
        composition to sunitinib. Patients receiving any medications or substances that are strong
        inhibitors or inducers of cytochrome P450 3A4 (CYP3A4) are ineligible. (A list of potent
        CYP3A4 inducers or inhibitors can be found in Section 5.2.) An exception will be made for
        patients who are on ritonavir-based highly active antiretroviral therapy, in which case the
        starting dose of sunitinib will be modified as indicated in Sections 5.1.1 and 5.2.12.
        Every effort should be made to switch patients taking such agents or substances to other
        medications. A comprehensive list of medications and substances known or with the potential
        to alter the pharmacokinetics of sunitinib through CYP3A4 is provided.

        3.2.9 Pregnant women are excluded from this study because sunitinib angiogenesis inhibitor
        with the potential for teratogenic or abortifacient effects. Because there is an unknown
        but potential risk for adverse events in nursing infants secondary to treatment of the
        mother with sunitinib breastfeeding should be discontinued if the mother is treated with
        sunitinib.

        3.2.10 Patients who require therapeutic doses of Coumadin derivative anticoagulants such as
        warfarin are excluded. Low molecular weight heparin is permitted, provided the patient's
        prothrombin time (PT)/INR is less than or equal to 1.5. Coumadin doses of up to 2 mg daily
        are permitted for prophylaxis of thrombosis.

        3.2.11 Patients with a pre-existing thyroid abnormality who are unable to maintain thyroid
        function in the normal range with medication are ineligible.

        3.2.12 Patients with 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 are excluded.

        3.2.13 Patients with QTc prolongation (defined as a QTc interval equal to or greater than
        500 msec) or other significant electrocardiogram (ECG) abnormalities are excluded.

        3.2.14 Patients with poorly controlled hypertension (systolic blood pressure of 140 mmHg or
        higher or diastolic blood pressure of 91 mmHg or higher) are ineligible.

        3.2.15 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 PT INR is less than or equal to 1.5.

        3.2.16 Patients with human immunodeficiency virus (HIV) infection are eligible provided
        their cluster of differentiation 4 (CD4) count is greater than or equal to the
        institutional lower limit of normal (LLN) ( greater than or equal to 334 cells/uL).