Clinical Trial 20937

• Overview

  Study Title:

  A Multicenter, Phase II Trial of Pembrolizumab and Sunitinib In Refractory Advanced Thymic Carcinoma

  Summary:

  This phase II trial studies how well pembrolizumab and sunitinib malate work in treating participants with thymic cancer that has spread to other places in the body or cannot be removed by surgery and does not respond to treatment. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread. Sunitinib malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving pembrolizumab and sunitinib malate may work better in treating thymic cancer.

  Objective:

  Primary Objectives: * The primary objective is to evaluate the efficacy of pembrolizumab and sunitinib for the treatment of patients with thymic carcinoma that have progressed on prior platinum based chemotherapy as measured by objective response rate. Secondary Objectives: * To evaluate the safety profile and toxicity of combination pembrolizumab and sunitinib as per CTCAE v 4.0. * To evaluate the progression free survival (PFS) and overall survival (OS) of patients treated with combination pembrolizumab and sunitinib.

• Treatments

  Therapies:

  Immunotherapy; Therapy (NOS)

  Medications:

  Pembrolizumab (Keytruda); Sunitinib Malate (SU011248)

• Inclusion Criteria

  Inclusion Criteria:
  • Be willing and able to provide written informed consent
  • Histologically or cytologically-documented diagnosis of advanced (metastatic and/or unresectable) thymic carcinoma, for which no curative treatment (including surgery, radiation, or other) is available
  • Have experienced progressive disease after at least one previous regimen of platinum-based chemotherapy
  • Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
  • Availability of a recent formalin-fixed, paraffin-embedded (FFPE) tumor tissue block; a recently obtained archival FFPE tumor tissue block (if an FFPE tissue block cannot be provided, 15 unstained slides [10 minimum] will be acceptable) from a primary or metastatic tumor resection or biopsy can be provided if it was obtained within 3 years of trial screening; patients with tumor specimens older than 3 years may still be eligible if deemed so by study sponsor
  • Be willing to provide tissue from an on-treatment fine-needle aspiration (FNA) or core biopsy of a tumor lesion; subjects must consent to on-treatment biopsy prior to initiation of clinical trial, however in subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may still continue on study
  • Be willing to provide peripheral blood samples at screening and day 1 of cycle 2 and cycle 3 for correlative studies
  • Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
  • Life expectancy greater than 3 months
  • Ability to swallow and retain oral medication
  • No evidence of uncontrolled hypertension as documented by 2 baseline blood pressure (BP) readings taken at least 1 hour apart; the baseline systolic BP readings must be => Left ventricular ejection fraction (LVEF) >= lower limit of normal (LLN) as assessed by either multigated acquisition (MUGA) scan or echocardiogram (ECHO)
  • Adequate organ function within 28 days of treatment as defined in protocol
  • International normalized ratio (INR) or prothrombin time (PT) => Activated partial thromboplastin time (aPTT) => Female patient of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication; if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
  • Female patients of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study medication. Note: abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
  • Male patients of childbearing potential must agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy. Note: abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject

• Exclusion Criteria

  Exclusion Criteria:
  • Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment
  • Has received prior sunitinib or pembrolizumab therapy for the treatment of malignancy
  • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
  • Has a known history of active tuberculosis (TB) (Bacillus tuberculosis)
  • Hypersensitivity to pembrolizumab or sunitinib or any of their excipients
  • Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1 or who has not recovered (i.e., => Has a known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
  • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment; this exception does not include carcinomatous meningitis which is excluded regardless of clinical stability
  • Has active autoimmune disease, including myasthenic syndrome, which has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs); replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
  • Has an active infection requiring systemic therapy
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
  • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
  • Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
  • Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected)
  • Has received a live vaccine within 30 days of planned start of study therapy. Note: seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines, and are not allowed
  • Significant proteinuria at baseline (> 500 mg/ 24 h, or > 2+ on spot analysis)
  • Additional exclusions apply

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