Renal Cell Carcinoma Articles

Articles

  • Immunotherapy: incorporation in the evolving paradigm of renal cancer management and future prospects.

    Significant progress has been made in the management of renal cell carcinoma (RCC) during the last few decades. In early stage, localized disease, surgical resection remains the modality of choice, with no therapeutic interventions as options for post-operative therapy other than simple observation and clinical surveillance.

    Published January 12, 2017
  • Impact of baseline visceral fat accumulation on prognosis in patients with metastatic renal cell carcinoma treated with systemic therapy.

    The aim of this study was to evaluate the clinical significance of visceral fat accumulation as a prognostic factor in patients with metastatic renal cell carcinoma (mRCC) treated with systemic therapies.

    Published February 20, 2017
  • Incidence and histologic features of mixed renal tumors.

    Guidelines for management of renal cell carcinoma (RCC) incompletely address the implications of mixed renal tumor histology. We investigate the incidence of mixed renal tumors identified at renal surgery and determine the association with pathologic features.

    Published October 26, 2017
  • Incidence of immune checkpoint inhibitor-related colitis in solid tumor patients: A systematic review and meta-analysis.

    Background: With the rising use of immune checkpoint inhibitors (ICI) across varying tumors types, immune-related colitis is an increasingly encountered, serious adverse event requiring appropriate management.

    Published November 14, 2017
  • Increased expression of CD44 is associated with more aggressive behavior in clear cell renal cell carcinoma.

    Although CD44 has been suggested as a prognostic marker in renal cell carcinoma (RCC), the prognostic significance of this marker in three main subtypes of RCC is still unclear. Thus, the present study was conducted to evaluate the expression and prognostic significance of CD44 as a cancer stem cell marker in different histological subtypes of RCC.

    Published December 18, 2017
  • Increased serum level of soluble interleukin-2 receptor is associated with a worse response of metastatic clear cell renal cell carcinoma to interferon alpha and sequential VEGF-targeting therapy.

    Renal cell carcinoma (RCC) is a tumor with immunogenic properties. Soluble interleukin-2 receptor (sIL-2R) has a role in T cell activation and may be important for immune regulation in various conditions, including infections, transplantation rejection, autoimmune inflammatory states, and cancer.

    Published June 1, 2017
  • Individualized dosing with axitinib: rationale and practical guidance.

    Axitinib is a potent, selective, vascular endothelial growth factor receptor inhibitor with demonstrated efficacy as second-line treatment for metastatic renal cell carcinoma. Analyses of axitinib drug exposures have demonstrated high interpatient variability in patients receiving the 5 mg twice-daily (b.

    Published December 29, 2017
  • Influence of Tyrosine Kinase Inhibitors on Hypertension and Nephrotoxicity in Metastatic Renal Cell Cancer Patients.

    Renal cell carcinoma (RCC) is one of the most common kidney malignancies. An upgraded comprehension of the molecular biology implicated in the development of cancer has stimulated an increase in research and development of innovative antitumor therapies.

    Published December 27, 2016
  • Influence of VEGFR single nucleotide polymorphisms on the efficacy of sunitinib therapy against renal cell carcinoma.

    Single nucleotide polymorphisms (SNPs) of vascular endothelial growth factor receptor (VEGFR) may have effects on the MAPK/ERK/STAT3 signaling pathway, and the resulting phenotypes may influence the response to sunitinib-targeted therapy for renal cell carcinoma.

    Published February 2, 2017
  • Integration of Recurrent Somatic Mutations with Clinical Outcomes: A Pooled Analysis of 1049 Patients with Clear Cell Renal Cell Carcinoma.

    Analyses of associations between clinicopathologic outcomes and recurrent somatic mutations in clear cell renal cell carcinoma (ccRCC) have been limited to individual cohorts.

    To define clinicopathologic associations between specific mutations and ccRCC disease characteristics.

    Published August 10, 2017
  • Is Change in Hemoglobin Level a Predictive Biomarker of Tyrosine Kinase Efficacy in Metastatic Renal Cell Carcinoma? A Turkish Oncology Group Study.

    There are insufficient predictive markers for renal cell carcinoma (RCC).

    A total of 308 metastatic RCC patients were analyzed retrospectively.

    The increased hemoglobin (Hb) group had significantly higher progression-free survival and overall survival (OS) compared with the decreased Hb group at 11.

    Published March 30, 2017
  • Laparoscopic Partial Nephrectomy Supported by Training Involving Personalized Silicone Replica Poured in Three-Dimensional Printed Casting Mold.

    Most kidney neoplasms are found incidentally and qualify for nephron-sparing surgery. Laparoscopic approach is beneficial to these patients because of its minimally invasive approach. However, these operations are both difficult and require plenty of experience and extended training.

    Published January 8, 2017
  • Laser desorption/ionization MS imaging of cancer kidney tissue on silver nanoparticle-enhanced target.

    Renal cell carcinoma is a very aggressive and often fatal disease for which there are no specific biomarkers found to date. The purpose of work was to find substances that differentiate the cancerous and healthy tissue by using laser desorption/ionization MS imaging combined with silver nanoparticle-enhanced target.

    Published December 22, 2017
  • Long-term benefit of sunitinib in patients with metastatic renal cell carcinoma in Latin America: retrospective analysis of patient clinical characteristics.

    To describe the clinical characteristics of Latin American patients with metastatic renal cell carcinoma (mRCC) who experienced a progression-free survival (PFS) for at least 15 months following treatment with sunitinib.

    Published December 27, 2016
  • Low preoperative serum cholesterol level is associated with aggressive pathologic features and poor cancer-specific survival in patients with surgically treated renal cell carcinoma.

    The prognostic implications of preoperative serum total cholesterol (TC) level in patients with renal cell carcinoma (RCC) remain poorly understood. We investigated the prognostic role of preoperative serum TC in patients with surgically treated RCC from a large, multi-institutional Korean collaboration.

    Published August 17, 2017
  • Lymphatic drainage from renal tumors in vivo: a prospective sentinel node study using SPECT/CT imaging.

    Lymphatic drainage from renal tumors is unpredictable and in vivo drainage studies of primary lymphatic landing sites may reveal the variability and dynamics of lymphatic connections. The purpose of this study was to investigate the lymphatic drainage pattern from renal tumors in vivo with SPECT/CT imaging after intra-tumoral radiotracer injection.

    Published December 15, 2017
  • Management of Atypical Renal Cell Carcinomas.

    Non-clear cell renal cell carcinoma (RCC) encompasses a diverse group of diseases, with research yielding different histologic findings and genetic profiles with each distinct subgroup. Simply mirroring the management techniques of clear cell RCC and borrowing from its growing armamentarium of therapeutic agents, while somewhat productive at first, but will ultimately be limiting.

    Published September 19, 2017
  • Metabolic Syndrome Negatively Impacts the Outcome of Localized Renal Cell Carcinoma.

    The aim of this study was to analyze the impact of metabolic syndrome (MetS) on outcome of patients with localized renal cell carcinoma (RCC). A retrospective database was compiled consisting of 646 patients who underwent surgery for localized RCC between 2005 and 2014.

    Published March 14, 2017
  • Metastatic polyp of the gallbladder from renal cell carcinoma.

    Gallbladder metastasis from renal cell carcinoma (RCC) is extremely rare. The purpose of this study is to clarify the characteristics of metastatic RCC to gallbladder.

    The pooled data for analysis were collected from the case of metastatic RCC to gallbladder encountered by our institution along with sporadic cases reported in literature from 1991 to 2015.

    Published April 12, 2017
  • Metastatic renal cell carcinoma: Patterns and predictors of metastases-A contemporary population-based series.

    To assess the patterns and predictors of metastatic disease in renal cell carcinoma (RCC) at the time of diagnosis in a contemporary series.

    The Surveillance, Epidemiology, and End Results database was queried for all patients with kidney RCC from 2010 to 2013 (N = 50,815).

    Published August 4, 2017
  • microRNA-210-3p depletion by CRISPR/Cas9 promoted tumorigenesis through revival of TWIST1 in renal cell carcinoma.

    Previous studies showed that five miRNAs (miR-885-5p, miR-1274, miR-210-3p, miR-224 and miR-1290) were upregulated the most in clear cell renal cell carcinoma (ccRCC). Our focus was to understand from a clinical standpoint the functional consequences of upregulating miR-210-3p.

    Published February 5, 2017
  • MicroRNAs Associated with Von Hippel-Lindau Pathway in Renal Cell Carcinoma: A Comprehensive Review.

    Renal cell carcinoma (RCC) are the most common renal neoplasia and can be divided into three main histologic subtypes, among which clear cell RCC is by far the most common form of kidney cancer. Despite substantial advances over the last decade in the understanding of RCC biology, surgical treatments, and targeted and immuno-therapies in the metastatic setting, the prognosis for advanced RCC patients remains poor.

    Published November 27, 2017
  • Microvascular and lymphovascular tumor invasion are associated with poor prognosis and metastatic spread in renal cell carcinoma: A validation study in clinical practice.

    To validate microvascular (MVI) and lymphovascular (LVI) invasion as a prognostic factor in renal cell carcinoma patients (pts.) MATERIALS AND METHODS: Data of patients with RCC who underwent radical or nephron sparing surgery were prospectively collected from three academic centers.

    Published August 25, 2017
  • Multimodal treatment of advanced renal cancer in 2017.

    in the last decades, the treatment of renal cell carcinoma has become more complex due to the introduction of novel systemic agents and the improvement of the loco-regional therapies that prolong survival maintaining a good quality of life.

    Published October 3, 2017
  • Multiple pulmonary emboli as a result of renal cell carcinoma: A case report.

    Pulmonary embolism is the most prevalent and potentially fatal complication of deep vein thrombosis. Renal cell carcinoma (RCC) is occasionally associated with pulmonary embolism, occurring as a result of secondary hypercoagulable states or cancer-associated emboli.

    Published February 2, 2017
  • Mutations in the Mitochondrial ND1 Gene Are Associated with Postoperative Prognosis of Localized Renal Cell Carcinoma.

    We analyzed mutations in the mitochondrial ND1 gene to determine their association with clinicopathological parameters and postoperative recurrence of renal cell carcinoma (RCC) in Japanese patients.

    Published December 28, 2016
  • Natural History of Complex Renal Cysts: Clinical Evidence Supporting Active Surveillance.

    To evaluate intervention rates, progression and cancer-specific survival outcomes of patients with complex renal cysts in a single center experience.

    A radiology data-mining system (Montage; Montage Healthcare Systems, Philadelphia, PA, USA) was used to retrospectively identify all reported cases of "complex renal cyst" in our institution (2001-2013).

    Published October 5, 2017
  • Neutrophil-lymphocyte ratio as a predictive biomarker for response to high dose interleukin-2 in patients with renal cell carcinoma.

    Immunotherapy with high-dose interleukin-2 (HD-IL2) results in long-term survival in some metastatic renal cell carcinoma (mRCC) patients but has significant acute toxicities. Biomarkers predicting response to therapy are needed to better select patients most likely to benefit.

    Published January 11, 2017
  • Nivolumab versus everolimus in advanced renal cell carcinoma: Japanese subgroup analysis from the CheckMate 025 study.

    Nivolumab improved overall survival (OS) and objective response rate (ORR) versus everolimus in previously treated patients with advanced renal cell carcinoma in the phase III CheckMate 025 study (minimum follow-up: 14 months).

    Published April 28, 2017
  • Novel immunotherapy in metastatic renal cell carcinoma.

    Despite the rapid development of therapeutic modalities for metastatic renal cell carcinoma (mRCC) over the past decade to include a number of targeted antiangiogenic therapies and traditional immunotherapy, such as high-dose interleukin-2 and interferon-α, mRCC continues to be associated with poor prognosis.

    Published July 13, 2017
  • Obesity as defined by waist circumference but not body mass index is associated with higher renal mass complexity.

    Obesity, typically defined as a body mass index (BMI)≥30kg/m(2), is an established risk factor for renal cell carcinoma (RCC) but is paradoxically linked to less advanced disease at diagnosis and improved outcomes.

    Published August 16, 2017
  • One-month assessment of renal cell carcinoma treated by everolimus using FDG PET/CT predicts progression-free and overall survival.

    We evaluated (18)F-2-fluoro-2-deoxyglucose positron emission tomography/computed tomography (FDG PET/CT) results as outcome predictors for patients with metastatic renal cell carcinoma (RCC) treated by everolimus (EVL), an inhibitor of mammalian target of rapamycin.

    Published March 30, 2017
  • Osteonecrosis of the Jaws in Patient Received Bisphosphonates and Sunitinib Separately: A Case Report.

    Recently published reports have suggested that antiangiogenic drugs such as sunitinib could potentiate the osteonecrosis of the jaw (ONJ) induced by bisphosphonates (BPs) and even induce this adverse effect per se.

    Published October 17, 2017
  • Outcomes of Patients With Long-Term Treatment Response to Vascular Endothelial Growth Factor-Targeted Therapy for Metastatic Renal Cell Cancer.

    Although targeted therapies with inhibitors of the vascular endothelial growth factor (VEGF) are the mainstay of treatment for metastatic renal cell carcinoma, there are limited data on the outcome of patients with long-term response to this treatment.

    Published July 26, 2017
  • Overall survival in renal cell carcinoma after introduction of targeted therapies: a Norwegian population-based study.

    This population-wide retrospective, non-interventional registry study assessed changes in overall survival (OS) and factors influencing OS in Norwegian patients with renal cell carcinoma (RCC).

    Two population-wide health registries were used to identify all RCC patients with (mRCC) or without metastases diagnosed before (2002-2005) and after (2006-2008 and 2009-2011) introduction of targeted therapies.

    Published February 8, 2017
  • Overall survival of 1st-line axitinib in metastatic renal cell carcinoma: Japanese subgroup analysis from phase II study.

    Subgroup analyses of a randomized global phase II study of axitinib showed objective response rate of 66% and median progression-free survival of 27.6 months in treatment-naïve Japanese patients with metastatic renal cell carcinoma (RCC).

    Published March 20, 2017
  • Overcoming intratumoural heterogeneity for reproducible molecular risk stratification: a case study in advanced kidney cancer.

    Metastatic clear cell renal cell cancer (mccRCC) portends a poor prognosis and urgently requires better clinical tools for prognostication as well as for prediction of response to treatment. Considerable investment in molecular risk stratification has sought to overcome the performance ceiling encountered by methods restricted to traditional clinical parameters.

    Published July 7, 2017
  • Overexpression of placenta specific 8 is associated with malignant progression and poor prognosis of clear cell renal cell carcinoma.

    Placenta specific 8 (PLAC8) plays an important role in many different cellular processes and human diseases, including multiple types of cancer. However, the functional role of PLAC8 in clear cell renal cell carcinoma (ccRCC) has never been elucidated.

    Published April 3, 2017
  • Overriding TKI resistance of renal cell carcinoma by combination therapy with IL-6 receptor blockade.

    Metastatic renal cell carcinoma (RCC) is a tumor entity with poor prognosis due to limited therapy options. Tyrosine kinase inhibitors (TKI) represent the standard of care for RCCs, however a significant proportion of RCC patients develop resistance to this therapy.

    Published August 7, 2017
  • p53-expression in patients with renal cell carcinoma correlates with a higher probability of disease progression and increased cancer-specific mortality after surgery but does not enhance the predictive accuracy of robust outcome models.

    Due to lacking external validation, molecular biomarkers are currently not applied for risk-stratification of patients with localized renal cell carcinoma. The objective of this study was to externally validate a molecular multi-marker panel included in a previously proposed prognostic nomogram for the prediction of postoperative disease-free survival.

    Published December 12, 2017
  • Partial Nephrectomy is Associated with Higher Risk of Relapse Compared with Radical Nephrectomy for Clinical Stage T1 Renal Cell Carcinoma Pathologically Upstaged to T3a.

    We aimed to study recurrence-free survival after partial versus radical nephrectomy for clinical stage T1 renal cell carcinoma among all comers and those upstaged to pathologic stage T3a.

    A retrospective review of 1250 patients undergoing partial nephrectomy or radical nephrectomy for clinically localized T1 renal cell carcinoma between 2006 and 2014 was performed.

    Published April 1, 2017
  • Partial nephrectomy margin imaging using structured illumination microscopy.

    Partial nephrectomy (PN) is the recommended procedure over radical nephrectomy (RN) for patients with renal masses < 4 cm in diameter (Stage T1a). Patients with > 4 cm renal masses can also be treated with PN, but have a higher risk for positive surgical margins.

    Published August 29, 2017
  • Pathologic analysis of non-neoplastic parenchyma in renal cell carcinoma: a comprehensive observation in radical nephrectomy specimens.

    This study provides a comprehensive examination of the histological features of non-neoplastic parenchyma in renal cell carcinoma (RCC). We prospectively collected radical nephrectomy (RN) specimens, to analyze the histological changes within peritumoral and distant parenchyma.

    Published January 3, 2018
  • Pathologic and Clinical Characteristics of Early Onset Renal Cell Carcinoma.

    The majority of RCCs occur within the 7th decade of life, uncommonly arising in adults ≤46years. We reviewed the clinicopathologic features of early-onset renal cell carcinoma (RCC) and evaluated the role of immunohistochemistry (IHC) in potentially identifying diagnoses of newly recognized RCC subtypes that may have been previously misclassified.

    Published December 1, 2017
  • Pazopanib for Metastatic Renal Cell Carcinoma: A Registry-based Analysis of 426 Patients.

    Pazopanib is approved for the first-line treatment of patients with metastatic renal cell carcinoma (mRCC). The present study was a retrospective registry-based analysis of 426 patients with mRCC treated with pazopanib as first-line targeted therapy.

    Published January 4, 2018
  • PD-L2: A prognostic marker in chromophobe renal cell carcinoma?

    In the context of cancer immunotherapy, PD-1 as well as PD-L1 has been widely studied in renal cell carcinoma (RCC). PD-1 and PD-L1 play a significant role as prognostic markers in clear cell renal cell carcinoma.

    Published April 4, 2017
  • Perinephric and Sinus Fat Invasion in Stage pT3a Tumors Managed by Partial Nephrectomy.

    We evaluated the influence of perinephric fat invasion (PFI) compared with sinus fat invasion (SFI) on disease-free survival (DFS) and cancer-specific survival (CSS) after partial nephrectomy (PN) for stage pT3a renal cell carcinoma (RCC).

    Published August 22, 2017
  • Perioperative and Oncologic Outcomes of Nephrectomy and Caval Thrombectomy Using Extracorporeal Circulation and Deep Hypothermic Circulatory Arrest for Renal Cell Carcinoma Invading the Supradiaphragmatic Inferior Vena Cava and/or Right Atrium.

    Radical nephrectomy (RN) and caval thrombectomy (CT) for renal cell carcinoma, with extracorporeal circulation (ECC) and deep hypothermic circulatory arrest (DHCA) is a challenging surgical approach.

    Published September 26, 2017
  • Phase I study of axitinib and everolimus in metastatic solid tumours and extension to metastatic renal cell carcinoma: Results of EVAX study.

    Anti-angiogenic and mammalian target of rapamycin inhibitors have shown efficacy in solid tumours. Reported combination of both drugs was deemed to be too toxic. Due to a potential favourable safety profile of axitinib (AX), a phase I study combining everolimus (EV) and AX for solid tumours was explored.

    Published September 11, 2017
  • Phase I/II Study of Pembrolizumab and Cabozantinib in Patients With Metastatic Renal Cell Carcinoma

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    Phase I/II Study of Pembrolizumab and Cabozantinib in Patients With Metastatic Renal Cell Carcinoma


    Condition: Metastatic Renal Cell Carcinoma

    Intervention:

    • Drug: Cabozantinib
    • Drug: Pembrolizumab

    Purpose: This is a phase I/II open-label study designed to evaluate the combination of pembrolizumab and cabozantinib in subjects with locally advanced, recurrent, or metastatic renal cell carcinoma. Sequential dose escalation of cabozantinib with standard dose pembrolizumab will occur in the phase I dose escalation part of the study to determine the recommended phase 2 dose (RP2D). Subsequently, subjects will receive cabozantinib at the RP2D in combination with pembrolizumab in the phase II dose expansion part of the study.

    Study Type: Interventional

    Clinical Trials Identifier NCT 8-digits: NCT03149822

    Sponsor: University of Colorado, Denver

    Primary Outcome Measures:

    • Measure: Efficacy of Pembrolizumab and Cabozantinib Based on Objective Response Rate
    • Time Frame: Beginning of study to end of study, up to 5 years
    • Safety Issue:

    Secondary Outcome Measures:

    • Measure: Maximally Tolerated Dose (MTD)
    • Time Frame: Throughout Cycle 1, up to 21 days
    • Safety Issue:
    • Measure: Recommended Phase 2 Dose
    • Time Frame: Throughout Cycle 1, up to 21 days
    • Safety Issue:
    • Measure: Dose Limiting Toxicities
    • Time Frame: Throughout Cycle 1, up to 21 days
    • Safety Issue:
    • Measure: Progression-Free Survival
    • Time Frame: Beginning of study to end of study, or death, whichever comes first, up to 5 years
    • Safety Issue:
    • Measure: Progression of Overall Disease
    • Time Frame: Beginning of study to end of study, or death, whichever comes first, up to 5 years
    • Safety Issue:
    • Measure: Progression of Bone Metastasis or Skeletal Related Event (SRE)
    • Time Frame: Beginning of study to end of study, or death, whichever comes first, up to 5 years
    • Safety Issue:
    • Measure: Clinical Benefit Rate
    • Time Frame: Beginning of study to end of study, or death, whichever comes first, up to 5 years
    • Safety Issue:
    • Measure: Duration of Disease Stability
    • Time Frame: Beginning of study to end of study, or death, whichever comes first, up to 5 years
    • Safety Issue:
    • Measure: Duration on Treatment in Subjects Beyond Treatment Progression
    • Time Frame: Beginning of study to end of study, or death, whichever comes first, up to 5 years
    • Safety Issue:

    Estimated Enrollment: 55

    Study Start Date: September 28, 2017

    Phase: Phase 1/Phase 2

    Eligibility:

    • Age: minimum 18 Years maximum 100 Years
    • Gender: All

    Inclusion Criteria:

    • 1. Subjects must have histological or cytological documentation of locally advanced, recurrent, or metastatic renal cell carcinoma. 2. Be willing and able to provide written informed consent/assent for the trial. 3. Stated willingness to complywith all study procedures and be available for the duration of the trial. 4. Be ≥ 18 years of age on day of signing informed consent. 5. Have measurable or evaluable disease based on RECIST 1.1. 6. Recovery to baseline or ≤ Grade 1 CTCAE v.4.0 from toxicities related to any prior treatments, unless AE(s) are clinically non-significant and/or stable on supportive therapy. 7. Confirmed availability of representative archival tumor specimens in paraffin blocks (preferred) or ≥ 10 unstained slides, with an associated pathology report.
    • Acceptable samples include core needle biopsies for deep tumor tissue or excisional, incisional, or punch biopsies for cutaneous, subcutaneous, or mucosal lesions.
    • Tumor tissue from bone metastases is not evaluable for PD-L1 expression and is therefore not acceptable.
    • A subject with insufficient or unavailable archival tissue may be eligible, upon discussion with the Principal Investigator, if the subject is willing to consent to undergo a pretreatment core, punch, or excisional/incisional biopsy sample collection of the tumor. 8. Have a performance status of 0 or 1 on the ECOG Performance Scale. 9. Demonstrate adequate organ function as defined by desired lab values. 10. Female subject 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. 11. Female subjects of childbearing potential (Section 5.7.2) must be willing to use an adequate method of contraception as outlined in Section 5.7.2
    • 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. 12. Male subjects of childbearing potential (Section 5.7.1) must agree to use an adequate method of contraception as outlined in Section 5.7.1- 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:

    • 1. 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. 2. Has a diagnosis of immunodeficiency or is receiving systemic steroiderapy equivalent to ≥ 10 mg/day of prednisone, or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. 3. Has a known history of active TB (Bacillus Tuberculosis) 4. Has had prior treatment with pembrolizumab. 5. Has had prior treatment with cabozantinib. 6. Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier. 7. 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., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
    • Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
    • Subjects with ≤ Grade 2 hypertension managed with medication are an exception to this criterion and may qualify for the study.
    • Subjects with ≤ Grade 2 endocrinopathy (e.g. hypothyroidism or adrenal insufficiency managed with medication) are an exception to this criterion and may qualify for the study. 8. Has had major surgery within 4 weeks or minor surgery within 2 weeks prior to study Day 1. Subjects must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy. 9. Prior treatment with immune checkpoint inhibitors is allowed, provided that no treatment-related Grade ≥ 3 adverse events (other than Grade 3 endocrinopathy managed with replacement therapy) were observed and at least a minimum of 28 days have elapsed between the last dose of prior treatment and the proposed Cycle 1 Day 1. 10. 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, carcinoma in situ or superficial bladder cancer, low-grade prostate cancer, intraductal papillary mucinous neoplasm (IPMN), and other low grade cancers that is suitable for active surveillance in the opinion of the investigator. 11. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Active CNS metastases will be defined as brain lesions that 1) require intervention with surgery, stereotactic radiosurgery (SRS), or whole brain radiotherapy (WBRT) or 2) require anti-epileptic therapy, systemic steroid treatment, or intrathecal therapy. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks after completion of focal therapy for brain metastases 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. 12. Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is allowed. 13. Has history of solid organ transplantation. 14. Has history of osteonecrosis of the jaw. 15. Has history of reversible posterior leukoencephalopathy syndrome. 16. Has history of wound dehiscence or complications requiring medical intervention within 6 months of study entry. 17. Has history of (non-infectious) pneumonitis that required steroids or active, non- infectious pneumonitis. 18. Has an active infection requiring systemic therapy with IV antibiotics. 19. Has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions: 1. Cardiovascular disorders:
    • Symptomatic congestive heart failure, unstable angina pectoris, serious cardiac arrhythmias.
    • Uncontrolled hypertension defined as sustained BP > 150 mm Hg systolic or > 100 mm Hg diastolic despite optimal antihypertensive treatment.
    • Stroke (including TIA), myocardial infarction, or other ischemic event, or thromboembolic event (e.g., deep venous thrombosis, pulmonary embolism) within 3 months before randomization. 2. Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation:
    • Tumors invading the GI-tract, active peptic ulcer disease, inflammatory bowel disease, diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis or acute obstruction of the pancreatic or biliary duct, or gastric outlet obstruction.
    • Abdominal fistula, gastrointestinal perforation, bowel obstruction, or intra-abdominal abscess within 6 months before randomization. Complete healing of an intra-abdominal abscess must be confirmed before study initiation. 3. Has clinically significant hematuria, hematemesis, or hemoptysis of > 0.5 teaspoon within 3 months before randomization. 4. Known endobronchial disease manifestation. Patients with suspected endobronchial disease on imaging who have no evidence of endobronchial disease on bronchoscopy are allowed. Patients with treated endobronchial disease are also allowed provided they are stable. 5. Lesions invading major pulmonary blood vessels. 20. 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. 21. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. 22. 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. 23. Has an inability to swallow tablets or capsules. 24. Has a previously identified allergy or hypersensitivity to components of the study treatment formulations. 25. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies). 26. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected). 27. 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.

    Contact:

    • Mary Anduha
    • 720-848-0659

    Locations:

    • University of Colorado Denver
    • Aurora Colorado 80045 United States
    • Memorial Hospital Central
    • Colorado Springs Colorado 80909 United States
    • Poudre Valley Hospital
    • Fort Collins Colorado 80528 United States
    • UCHealth Lone Tree Medical Center
    • Lone Tree Colorado 80124 United States

    View trial on ClinicalTrials.gov


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    Published June 20, 2018

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