Kidney/Renal Cancer

{{header-clinical-trials-navigation}}

MEDI4736 Combinations in Metastatic Renal Cell Carcinoma


Condition: Renal Clear Cell Carcinoma, Renal Papillary Cell Carcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02819596

Sponsor: Queen Mary University of London

Phase: Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  1. Written informed consent prior to performing any protocol-related procedures, including study specific screening procedures.
  2. Age ≥ 18 years at the time of study entry.
  3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
  4. Life expectancy ≥12 weeks
  5. Histologically confirmed advanced (not amenable to curative surgery or radiation therapy) or metastatic (stage IV) renal cell cancer with a component of either clear cell cancer or papillary cancer. Patients with a component of both must be enrolled into the cohort with the predominant tumour type.
  6. Clear cell renal cancer patients must have experienced progressive disease after exposure to Vascular Endothelial growth rate (VEGF) targeted therapy.
  7. Papillary cell renal cancer patients must be considered to be VEGF treatment naive or treatment refractory to be eligible.
  8. Evidence of measurable disease (i.e., ≥1 malignant tumour mass that can be accurately measured in at least 1 dimension ≥ 20 mm with conventional computerized tomography CT Scan or Magnetic Resonance Imaging (MRI), or ≥10 mm with spiral CT scan using a 5 mm or smaller contiguous reconstruction algorithm). Bone lesions, ascites, peritoneal carcinomatosis or miliary lesions, pleural or pericardial effusions, lymphangitis of the skin or lung, cystic lesions, or irradiated lesions are not considered measurable.
  9. Adequate normal organ, marrow and coagulation function as defined by the following criteria:
  10. Haemoglobin ≥ 9.0g/dL
  11. Absolute neutrophil count (ANC) ≥1.5 x 109/L (≥1500/L) without growth factor support
  12. Platelet count ≥ 100 x 109 /L (≥100,000/L)
  13. Total serum bilirubin ≤1.5 x institutional upper limit of normal (ULN) (this will not apply to subjects with confirmed Gilbert's syndrome [persistent or recurrent hyperbilirubinaemia that is predominantly unconjugated in the absence of haemolysis or hepatic pathology], who will be allowed only in consultation with their physician.
  14. Serum transaminases (AST/ALT) ≤2.5 x the institutional ULN.
  15. Glomerular filtration rate (GFR)FR ≥40mL/min as assessed using the standard methodology at the investigating sites (e.g. by Cockroft-Gault).
  16. International Normalisation Ration (INR) <1.5 x institutional ULN or activated partial thromboplastin time (aPTT) <1.5 x institutional ULN. This applies only to patients who do not receive therapeutic anti-coagulation.
  17. Representative formalin-fixed paraffin-embedded (FFPE) tumour block with an associated anonymised pathology report must be available for central testing and determined to be evaluable for tumour assessment of PD-L1 and Met. PD-L1 and Met related testing will be required prior to study entry only for the biomarker enrichment phase of the trial. (every effort should be made to obtain FFPE blocks however unstained fresh tissue slides and core needle biopsies will suffice)
  18. Patients with known tumour thrombus or deep vein thrombosis (DVT) are eligible if stable on low molecular weight heparin (LMWH) for ≥ 4 weeks.
  19. Negative serum or urine pregnancy test within 2 weeks prior to the first dose of IMP (for female patients of childbearing potential only). Non-childbearing potential is defined as:
  20. Post-menopausal defined as aged 50 years of age and amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments OR
  21. Documented irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation OR
  22. <50 years of age who have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatments and with Luteinizing hormone (LH) and Follicle Stimulating Hormone (FSH) levels within local institution post-menopausal ranges
  23. Agreement to use adequate contraceptive measures (Section 6.18).
  24. Ability to swallow and retain oral medications.
  25. Willing and able to comply with the protocol for the duration of the study including undergoing treatment, scheduled visits and examinations including follow up.

Exclusion Criteria:

  • 1. Participation in another clinical study with an investigational product within 28 days prior to enrolment in the study. 2. Any previous treatment with an anti−programmed death−1 (PD-1), or anti−PD-L1 therapeutic antibody (including MEDI4736), CD137 agonists, c-MET inhibitors or pathway-targeting agents, or CTLA-4. Patients with limited c-MET inhibitor exposure must be discussed with the study medical monitor. 3. Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumour embolization, monoclonal antibodies) within 2 weeks or five half-lives of the anti-cancer therapy prior to the first dose of study drug, or radical radiotherapy within 4 weeks prior to the first dose of study drug. 4. Patients receiving strong inducers of CYP3A4, strong inhibitors of CYP3A4 or CYP1A2 or CYP3A4 substrates which have a narrow therapeutic range within 2 weeks before the first dose of study treatment (3 weeks for St John's Wort) are excluded from enrolment in the study (see Appendix I). 5. Currently receiving treatment with therapeutic doses of warfarin sodium. LMWH is allowed. 6. Current or prior use of immunosuppressive medication within 21 days before the first dose of MEDI4736 or tremelimumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid. 7. Treatment with systemic immunostimulatory agents (including but not limited to interferons or interleukin [IL] −2) within 4 weeks or five half-lives of the drug, whichever is shorter, prior to enrolment. 8. Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving MEDI4736 or tremelimumab or anticipation that such a live, attenuated vaccine will be required during the study. 9. Symptomatic or uncontrolled brain metastases requiring concurrent treatment, inclusive of but not limited to surgery, radiation and/or corticosteroids. 10. History of another primary malignancy other than renal cell carcinoma within 3 years prior to Cycle 1, Day 1 with the exception of: 1. Malignancy treated with curative intent and with no known active disease ≥ 3 years before the first dose of study drug and of low potential risk for recurrence. 2. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease. 3. Adequately treated carcinoma in situ without evidence of disease e.g. cervical cancer in situ or localized prostate cancer treated with curative intent and absence of prostate-specific antigen (PSA) relapse or incidental prostate cancer (Gleason score ≤ 3 + 4 and PSA <10ng/mL undergoing active surveillance and treatment naive). Patients on surveillance for low risk prostate cancer are also eligible
  • please discuss with medical monitor. 11. Mean resting QT interval corrected for heart rate (QTc) >470ms calculated from triplicate electrocardiograms (ECGs). 12. Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results, including significant liver disease (such as cirrhosis, uncontrolled major seizure disorder, or superior vena cava syndrome). 13. Any unresolved toxicity of CTCAE grade >2 from previous anti-cancer therapy. Patients with irreversible toxicity that is not reasonably expected to be exacerbated by the IMP may be included e.g. hearing loss, peripheral neuropathy etc. 14. Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE >Grade 1. 15. Active or prior documented autoimmune disease within the past 2 years including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. NOTE: Subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded. Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid-replacement hormone may be eligible for this study. 16. Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis) or history of gastrointestinal disorders (medical disorders or extensive surgery) which may interfere with the absorption of the study drug 17. History of primary immunodeficiency 18. History of allogeneic prior allogeneic stem cell or solid organ transplant 19. History of hypersensitivity to MEDI4736, tremelimumab, or any excipient or history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins 20. History of hypersensitivity to savolitinib and its excipients. 21. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension (SBP>160mmHg or Diastolic blood pressure >100mmHg, patients with values above these levels must have their blood pressure controlled with medication prior to starting treatment), unstable angina pectoris, cardiac arrhythmia, or any factors that increase the risk of QTc prolongation, any clinically important abnormalities in rhythm, conduction or morphology of resting ECGs, active peptic ulcer disease or gastritis, Type I diabetes mellitus, active bleeding diatheses including any subject known to have evidence of acute or chronic hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent 22. Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within 3 months prior to enrolment, Patients with a known left ventricular ejection fraction (LVEF) < 40% will be excluded. 23. Major surgical procedure within 4 weeks prior to enrolment, minor surgical procedure within 7 days of enrolment or anticipation of need for a major surgical procedure during the course of the study other than for diagnosis 24. History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest CT scan (History of radiation pneumonitis in the radiation field (fibrosis) is permitted). 25. Active tuberculosis or known history of previous clinical diagnosis of tuberculosis. 26. History of leptomeningeal carcinomatosis 27. Female subjects who are pregnant or breast-feeding 28. Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

Alternative Schedule Sunitinib in Metastatic Renal Cell Carcinoma: Cardiopulmonary Exercise Testing


Condition: Carcinoma, Renal Cell

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03109015

Sponsor: Duke University

Phase: Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • 1. Age ≥ 18 years. 2. Histologically confirmed renal cell carcinoma (RCC) 3. One of the two following populations: 1. High risk for recurrence of RCC after nephrectomy, in the opinion of the investigator, OR 2. Locally advanced, unresectable or metastatic disease, in the opinion of the investigator, and good or intermediate risk by IDMC Heng Criteria (see Appendix I). 4. Karnofsky Performance Status (KPS) ≥ 80 (see Appendix A) 5. Good or intermediate risk by IDMC Heng Criteria (see Appendix I).4 6. Appropriate for treatment with sunitinib in the opinion of the treating physician. 7. Able to swallow sunitinib and comply with study requirements. 8. Able to walk and jog on a treadmill, in the opinion of the treating physician. 9. Must be able to complete an acceptable cardiopulmonary exercise test (CPET) at baseline (see Section 8.2), defined as at least one of the following:
  • Achieving a plateau in oxygen consumption concurrent with an increase in power output;
  • Respiratory exchange ratio ≥ 1.1 (RER);
  • Volitional exhaustion with a rating of perceived exertion ≥17 (RPE). 10. Subjects must have normal organ and marrow function as defined below:
  • Absolute neutrophil count ≥1,200/µL
  • Hemoglobin ≥9 g/dL
  • Platelets ≥75,000/µL
  • Total bilirubin ≤1.5 x institutional upper limit of normal
  • AST(SGOT)/ALT(SGPT) <2.5 x institutional upper limit of normal
  • Urine protein creatinine (UPC) ratio of <1 (see Appendix G schedule of events footnote)
  • Creatinine ≤2.0 OR creatinine clearance >30 mL/min/1.73 m2 for subjects with creatinine levels above institutional normal (see Appendix H).
  • Left ventricular ejection fraction (LVEF) ≥lower limit of institutional normal as assessed by echocardiography. 11. For the sixteen patients who elect to participate in the optional technology portion involving electronic step counts and blood pressure monitoring, the patient must have a Bluetooth-enabled smart phone, which is compatible with the wireless health monitors. 12. For women of childbearing potential (WOCBP) must have a negative serum pregnancy test prior to the start of the study. Women of childbearing potential (WOCBP) must agree to follow instructions for method(s) of contraception for the duration of the study. Medically acceptable contraceptives include: (1) surgical sterilization (such as a tubal ligation or hysterectomy), (2) approved hormonal contraceptives (such as birth control pills, patches, implants or injections), (3) barrier methods (such as a condom or diaphragm) used with a spermicide, or (4) an intrauterine device (IUD). Contraceptive measures such as Plan B (TM), sold for emergency use after unprotected sex, are not acceptable methods for routine use. If you do become pregnant during this study or if you have unprotected sex, you must inform your study physician immediately. 13. For men who are sexually active, must agree to use a two medically acceptable forms of birth control (one of which must include a condom as a barrier method of contraception) in order to be in this study. Medically acceptable contraceptives include: (1) surgical sterilization (such as a vasectomy), or (2) a condom used with a spermicide. Contraceptive measures such as Plan B (TM), sold for emergency use after unprotected sex, are not acceptable methods for routine use. Men must also agree to inform their partner of the potential for harm to an unborn child. She should know that if pregnancy occurs, the subject will need to report it to the study doctor, and she should promptly notify her doctor. The study doctor will ask if the subject's partner is willing to provide updates on the progress of the pregnancy and its outcome. If the subject's partner agrees, this information will be provided to Pfizer, Inc. for safety monitoring follow-up.

Exclusion Criteria:

  • 1. Any prior anti-VEGF therapies (i.e., sunitinib, sorafenib, pazopanib, axitinib, cabozantinib, bevacizumab, etc.), including in the adjuvant or neoadjuvant setting. 2. Prior systemic therapy for advanced RCC; however, treatment with immunotherapy (i.e., high-dose bolus IL-2, ipilumumab + nivolumab, etc.) is allowed. 3. Subjects who are receiving any other investigational agents. 4. Subjects who are receiving strong CYP3A4 inhibitors or CYP3A4 inducers (see Section 5.3.2.2). 5. Radiotherapy within 2 weeks prior to taking the first dose of study drug, or those who have not recovered from adverse events due to agents administered more than 2 weeks earlier. 6. Central nervous system (CNS) metastases at baseline, with the exception of those subjects who have previously treated CNS metastases (surgery ± radiotherapy, radiosurgery, or gamma knife) and who meet both of the following criteria: a) are asymptomatic, and b) have no requirement for steroids or enzyme-inducing anticonvulsants in the prior 28 days. 7. Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to:
  • Active peptic ulcer disease
  • Known intraluminal metastatic lesion(s) with risk of bleeding
  • Inflammatory bowel disease (e.g., ulcerative colitis, Crohn's disease) or other gastrointestinal conditions with increased risk of perforation
  • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to beginning study treatment 8. History of any one or more of the following cardiovascular conditions within the past 6 months:
  • Cardiac angioplasty or stenting
  • Myocardial infarction
  • Unstable angina
  • Coronary artery bypass graft surgery
  • Symptomatic peripheral vascular disease
  • Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA) (see Appendix J) 9. Absolute contraindications to cardiopulmonary exercise testing and/or aerobic training, as determined by the attending oncologist: Absolute Contraindications
  • Uncontrolled arrhythmia causing symptoms or hemodynamic compromise
  • Recurrent syncope
  • Active endocarditis
  • Acute myocarditis or pericarditis
  • Symptomatic severe aortic stenosis
  • Uncontrolled heart failure
  • Suspected dissecting aneurysm
  • Uncontrolled asthma
  • Pulmonary edema
  • Room air desaturation at rest <85%
  • Respiratory failure
  • Acute non-cardiopulmonary disorders that may affect exercise performance or be aggravated by exercise (i.e., infection, renal failure, thyrotoxicosis)
  • Mental impairment leading to inability to cooperate. 10. Poorly controlled hypertension [defined as systolic blood pressure (SBP) of >150 mmHg or diastolic blood pressure (DBP) of >90 mmHg]. 11. History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism, or untreated deep venous thrombosis (DVT) within the past 6 months. 12. Major surgery or trauma within 28 days prior to first dose of investigational product and/or presence of any non-healing wound, fracture, or ulcer (procedures such as catheter placement are not considered to be major surgery). 13. Osseous metastatic disease with unacceptable risk of impending fracture due to study assessments, in the opinion of the investigator 14. Evidence of active bleeding or bleeding diathesis. 15. Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels that increase the risk of pulmonary hemorrhage.

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

A Phase 1/2a Study of BMS-986205 Administered in Combination With Nivolumab (Anti-PD-1 Monoclonal Antibody) and in Combination With Both Nivolumab and Ipilimumab (Anti-CTLA-4 Monoclonal Antibody) in Advanced Malignant Tumors


Condition: Advanced Cancer, Melanoma, Non-Small Cell Lung Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02658890

Sponsor: Bristol-Myers Squibb

Phase: Phase 1/Phase 2

Eligibility:

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

Inclusion Criteria:

  • During dose escalation, subjects with advanced solid tumors that have progressed following at least one standard regimen
  • During cohort expansion, subjects with advanced cancer that either have received at least one prior therapy or are treatment naive, depending on the specified tumor type
  • Subjects must have measurable disease
  • Subject must consent to provide previously collected tumor tissue and a tumor biopsy during screening.
  • At least 4 weeks since any previous treatment for cancer
  • Must be able to swallow pills or capsules
  • Eastern Cooperative Oncology Group(ECOG) Performance Status 0-1 Exclusion Criteria:
  • Active or chronic autoimmune diseases
  • Uncontrolled or significant cardiovascular disease
  • History of any chronic Hepatitis, active Hepatitis B or C, human immunodeficiency virus (HIV), or acquired immune deficiency syndrome (AIDS)
  • Chronic hepatitis: Positive test for Hepatitis B virus surface antigen or Hepatitis C antibody (except for subjects with hepatocellular carcinoma)
  • Active central nervous system (CNS) metastases and CNS metastases as the only sites of disease
  • Active infection Other protocol defined inclusion/

Exclusion Criteria:

  • Active or chronic autoimmune diseases
  • Uncontrolled or significant cardiovascular disease
  • History of any chronic Hepatitis, active Hepatitis B or C, human immunodeficiency virus (HIV), or acquired immune deficiency syndrome (AIDS)
  • Chronic hepatitis: Positive test for Hepatitis B virus surface antigen or Hepatitis C antibody (except for subjects with hepatocellular carcinoma)
  • Active central nervous system (CNS) metastases and CNS metastases as the only sites of disease
  • Active infection Other protocol defined inclusion/exclusion criteria could apply

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

A Phase III, Multicenter, Randomized, Placebo-Controlled, Double-Blind Study of Atezolizumab (Anti−PD-L1 Antibody) as Adjuvant Therapy in Patients With Renal Cell Carcinoma at High Risk of Developing Metastasis Following Nephrectomy


Condition: Renal Cell Carcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03024996

Sponsor: Hoffmann-La Roche

Phase: Phase 3

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • ECOG performance status of less than or equal to (
  • Pathologically confirmed RCC with a component of either clear cell histology or sarcomatoid histology that has not been previously treated in the adjuvant or neoadjuvant setting and classified as being at high risk of RCC recurrence
  • Radical or partial nephrectomy with lymphadenectomy in select participants
  • Absence of residual disease and absence of metastasis, as confirmed by a negative baseline computed tomography (CT) of the pelvis, abdomen, and chest no more than 4 weeks prior to randomization. Confirmation of disease-free status will be assessed by an independent central radiologic review of imaging data.
  • Absence of brain metastasis, as confirmed by a negative CT with contrast or magnetic resonance imaging (MRI) scan of the brain, no more than 4 weeks prior to randomization. Applicable only to metastasectomy participants
  • Full recovery from nephrectomy or metastasectomy within 12 weeks from randomization following surgery

Exclusion Criteria:

  • Bilateral synchronous tumors with inheritable forms of RCC including von Hippel-Lindau
  • Any approved anti-cancer therapy, including chemotherapy or hormonal therapy, within 3 weeks prior to initiation of study treatment
  • Treatment with any other investigational agent or participation in another clinical study with therapeutic intent within 28 days or five half-lives of the investigational agent, whichever is longer, prior to enrollment
  • Malignancies other than RCC within 5 years prior to Cycle 1, Day 1
  • History of autoimmune disease
  • Participants with prior allogeneic stem cell or solid organ transplantation
  • History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest CT scan
  • Positive test for HIV
  • Participants with active hepatitis B or hepatitis C
  • Active tuberculosis
  • Severe infections within 4 weeks prior to randomization including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
  • Major surgical procedure within 4 weeks prior to randomization or anticipation of need for a major surgical procedure during the course of the study other than for diagnosis
  • Administration of a live, attenuated vaccine within 4 weeks before Cycle 1, Day 1
  • Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the participant at high risk from treatment complications
  • Prior treatment with cluster of differentiation (CD)137 agonists, anti-cytotoxic T-lymphocyte-associated protein-4 (anti-CTLA-4), anti-programmed death-1 (anti-PD−1), or anti-programmed death-ligand 1 (anti-PD-L1) therapeutic antibody or pathway-targeting agents
  • Treatment with systemic immunostimulatory agents (including but not limited to interferons or interleukin-2) within 6 weeks or five half-lives of the drug, whichever is shorter, prior to randomization
  • Treatment with systemic immunosuppressive medications (including but not limited to corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti−tumor necrosis factor agents) within 2 weeks prior to randomization or anticipated need for systemic immunosuppressive medications during the study

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

A Randomized, Phase II Efficacy Assessment of Multiple MET Kinase Inhibitors (Cabozantinib [NSC #761968], Crizotinib [NSC #749005], Savolitinib [NSC #785348], and Sunitinib [NSC #736511]) in Metastatic Papillary Renal Carcinoma (PAPMET)


Condition: Stage III Renal Cell Cancer AJCC v7, Stage IV Renal Cell Cancer AJCC v7, Type 1 Papillary Renal Cell Carcinoma, Type 2 Papillary Renal Cell Carcinoma, Unresectable Renal Cell Carcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02761057

Sponsor: National Cancer Institute (NCI)

Phase: Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • Patients must have histologically or cytologically confirmed papillary histology renal cell carcinoma which is metastatic or locally advanced disease not amenable to surgical resection; (NOTE: a designation of type I or type II should be made by the local pathologist if possible); mixed histologies containing type I or type II will be allowed provided that they contain >= 50% of the papillary component
  • Patients must also have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension; disease X-rays, scans or physical examinations used for tumor measurement must have been completed within 28 days prior to registration; if there is clinical suspicion for bone metastases at the time of enrollment (at the discretion of the investigator), bone scan should be performed at baseline (within 42 days prior to registration); all disease must be assessed and documented on the Baseline Tumor Assessment form
  • Patients with a history of treated brain metastases who are asymptomatic and have not received steroid therapy in the 14 days prior to registration are eligible; anti-seizure medications are allowed provided they are non-enzyme inducing (e.g. topiramate, levetiracetam, gabapentin)
  • Patients must not have cavitating pulmonary lesions; patients must not have tumor invading the gastrointestinal (GI) tract or evidence of endotracheal or endobronchial tumor within 28 days prior to registration
  • Patients may have received prior surgery; at least 28 days must have elapsed since surgery and patient must have recovered from any adverse effects of surgery
  • Patients may have received up to one prior systemic therapy for advanced or metastatic renal cell carcinoma with the exception of another VEGF inhibitor Food and Drug Administration (FDA)-approved for advanced RCC (i.e., pazopanib, bevacizumab, sorafenib or axitinib); if a patient develops metastatic disease within six months of discontinuation of adjuvant therapy, this will constitute one prior systemic therapy for advanced or metastatic renal cell carcinoma (RCC); if a patient develops metastatic disease and more than six months has elapsed since discontinuation of adjuvant therapy, this will not constitute prior systemic therapy for advanced or metastatic RCC; patients may have also received prior immunotherapy; patients must not have received a MET/hepatocyte growth factor (HGF) inhibitor or sunitinib as prior therapy; at least 14 days must have elapsed since completion of prior systemic therapy; patients must have recovered from all associated toxicities at the time of registration
  • Patients may have received prior radiation therapy, but must have measurable disease outside the radiation port; at least 14 days must have elapsed since completion of prior radiation therapy; patients must have recovered from all associated toxicities at the time of registration
  • Patients must not be taking, nor plan to take while on protocol treatment, strong CYP3A4 inhibitors (e.g. boceprevir, cobicistat, danoprevir, elvitegravir/RIT, fluvoxamine, indinavir, itraconazole, ketoconazole, lopinavir/RIT, nefazodone, nelfinavir, posaconazole, ritonavir, telaprevir, telithromycin, tipravavir/RIT, or voriconazole); strong CYP3A4 inducers (e.g. avasimibe, phenytoin, rifampin, rifabutin); potent inhibitors of CYP1A2 (e.g. ciprofloxacin); and/or drugs known to be CYP3A4 substrates with a narrow therapeutic range (e.g., diergotamine, ergotamine) within 14 days prior to randomization; moderate inhibitors or inducers of isoenzyme CYP3A4 should be avoided, but if necessary can be used with caution
  • Patients must not be receiving or planning to receive any other investigational agents
  • Patients must have a complete physical examination and medical history within 28 days prior to registration
  • Patients must have a Zubrod performance status of 0
  • 1
  • White blood cell count (WBC) >= 2,000/mcL (must be obtained within 28 days prior to registration)
  • Absolute neutrophil count (ANC) >= 1,000/mcL (must be obtained within 28 days prior to registration)
  • Platelet count >= 75,000/mcL (must be obtained within 28 days prior to registration)
  • Serum bilirubin =< 1.5 x institutional upper limits of normal (ULN) (must be obtained within 28 days prior to registration)
  • Serum transaminase (serum glutamic oxaloacetic transaminase [SGOT]/aspartate aminotransferase [AST] and serum glutamate pyruvate transaminase [SGPT]/alanine aminotransferase [ALT]) must be =< 2.5 x the institutional ULN unless the liver is involved with the tumor, in which case serum transaminase (SGOT/SGPT) must be =< 5 x the institutional ULN (must be obtained within 28 days prior to registration)
  • Serum creatinine must be =< 2 x the institutional ULN OR creatinine clearance (either measured or calculated) must be > 30 mL/min (must be obtained within 28 days prior to registration)
  • Patients must not have any clinical evidence of congestive heart failure (CHF) (specifically, New York Heart Association [NYHA] class III [moderate] or class IV [severe]) at the time of registration; baseline echocardiogram within 28 days of registration must demonstrate an ejection fraction (EF) >= 50%; due to the potential cardiac toxicity of the agents utilized in this protocol, patients must have corrected QT (QTc) interval < 500 msec on prestudy electrocardiogram (EKG) and no known history of congenital long QT syndrome; patients must not have experienced unstable angina pectoris, clinically significant cardiac arrhythmias, or stroke (transient ischemic attack [TIA] or other ischemic event) within 3 months prior to registration and not have experienced myocardial infarction or thromboembolic event requiring anticoagulation within 6 months of registration; prestudy EKG must be obtained within 28 days prior to registration
  • Baseline urinalysis should show urine protein < 3+ and must be obtained within 28 days prior to registration; if urine protein is 3+ or greater, then urine protein by 24 hour collection must show less than 3 grams of protein
  • Patients must not have inadequately controlled hypertension; patients must have documented blood pressures of systolic blood pressure (SBP) < 150 and diastolic blood pressure (DBP) < 90 within 14 days of starting randomization; blood pressure medications (any number) are permitted
  • Patients must be able to take oral medications (i.e., swallow pills whole); patients must not have gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for intravenous (IV) alimentation, prior surgical procedures that could in the opinion of the treating investigator affect absorption, or active peptic ulcer disease; patients with intractable nausea or vomiting are not eligible
  • Patients must not have had any clinically-significant GI bleeding within 6 months prior to registration and patients must not have a GI disorder which (at the discretion of the investigator) bears a high risk of perforation or fistula; examples of this include (but are not limited to) Crohn's disease or tumor with transmural extension through the gastrointestinal lining
  • Patients must not have had hemoptysis of >= 0.5 teaspoon (2.5 ml) of red blood within 3 months prior registration
  • Patients must not demonstrate any other signs indicative of pulmonary hemorrhage within 3 months prior to registration
  • Patient's baseline imaging must not indicate the presence of tumor invading or encasing any major blood vessels
  • Patients must not have any unresolved wounds from previous surgery
  • Albumin, alkaline phosphatase, bicarbonate, blood urea (BUN), chloride, glucose, phosphorus, and total protein must be assessed within 28 days of registration
  • No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for 3 years; men receiving active surveillance for prostate cancer may also be enrolled
  • Due to the unknown effects of the study drugs, patients must not be pregnant or nursing; women/men of reproductive potential must have agreed to use an effective contraceptive method while receiving study drug and for three months after last dose of study drug; a woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months; in addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation; however, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures
  • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with cabozantinib, crizotinib, savolitinib or sunitinib; in addition these patients are at increased risk of lethal infections when treated with marrow suppressive therapy; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
  • Patients must have tissue available and be willing to submit for independent pathologic review in order to classify type I versus type II papillary disease
  • Patients must be offered the opportunity to participate in specimen banking for future translational medicine studies
  • Patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines
  • As a part of the OPEN registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

caBozantinib in cOllectiNg ductS Renal Cell cArcInoma (BONSAI)


Condition: Collecting Duct Carcinoma (Kidney)

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03354884

Sponsor: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Phase: Phase 2

Eligibility:

  • Age: minimum 18 Years maximum 85 Years
  • Gender: All

Inclusion Criteria:

  • 1. Written Informed Consent Form 2. Unresectable, advanced or metastatic collecting ducts carcinoma untreated with any systemic agent for advanced disease 3. Measurable disease as defined by RECIST v1.1 criteria 4. Age ≥18 years 5. ECOG Performance Status 0-1 6. Any of the following laboratory test findings:
  • Hemoglobin > 9 g/dL (5.6 mmol/L)
  • WBC > 2,000/mm3
  • Neutrophils > 1,500/mm3
  • Platelets > 100,000/mm3
  • AST or ALT < 3 x ULN (< 5 x ULN if liver metastases are present)
  • Total Bilirubin < 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL)
  • Serum creatinine < 1.5 x upper limit of normal (ULN) or creatinine clearance ≥ 40 mL/min (measured or calculated by Cockroft-Gault formula)
  • Lipase < 2.0 x the upper limit of normal and no radiologic or clinical evidence of pancreatitis
  • PT-INR/PTT ≤ 1.5 x upper limit of normal [Patients who are being therapeutically anticoagulated with an agent such as coumadin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in these parameters exists.] For patients on warfarin, close monitoring of at least weekly evaluations will be performed, until INR is stable based on a measurement at pre-dose, as defined by the local standard of care 7. Availability of a representative FFPE tumor specimen collected within 24 months of starting first-line cabozantinib that enables the definitive diagnosis of CDC (the archival specimen must contain adequate viable tumor tissue to enable candidate biomarkers status; the specimen may consist of a tissue block or at least 15 unstained serial sections; for core needle biopsy specimens, at least two cores should be available for evaluation) 8. Sexually active fertile subjects and their partners must agree to use medically accepted methods of contraception (eg, barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the study and for 4 months after the last dose of study treatment 9. Female subjects of childbearing potential must not be pregnant at screening

Exclusion Criteria:

  1. Previous therapy for advanced disease; any medical adjuvant treatment must have been stopped at least six months before entry into the study
  2. History of any one or more of the following cardiovascular conditions within the past 6 months: cardiac angioplasty or stenting, myocardial infarction, unstable angina, coronary artery bypass graft surgery, symptomatic peripheral vascular disease, Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA)
  3. Poorly controlled hypertension [defined as systolic blood pressure (SBP) of ≥140 mmHg or diastolic blood pressure (DBP) of ≥ 90mmHg].
  4. History of cerebrovascular accidents, including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months. Note: Subjects with recent DVT who have been treated with therapeutic anti-coagulating agents for at least 6 weeks are eligible
  5. Major surgery or trauma within 28 days before to study entry; the such as catheter placement not considered to be major surgery).
  6. Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 3 months before randomization.
  7. Evidence of active bleeding or bleeding diathesis and/or clinically-significant GI bleeding within 6 months before the first dose of study treatment; 3 months for pulmonary hemorrhage and patients with tumor invading or encasing any major blood vessels.
  8. Patients with GI disorders associated with a high risk of perforation or fistula formation.
  9. Subjects with clinically relevant ongoing complications from prior radiation therapy.
  10. Any serious and/or unstable pre-existing medical, psychiatric, or other conditions that could interfere with subject's safety, provision of informed consent, or compliance to study procedures.
  11. Previous or ongoing treatment (except for adjuvant therapies) with any of the following anti-cancer therapies: chemotherapy, immunotherapy, target therapies, investigational therapy or hormonal therapy within 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of Cabozantinib
  12. Inability to swallow tablets or capsules.

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

A Phase 2, Open-Label, Single-Arm Study of Cabozantinib in Japanese Patients With Advanced Renal Cell Carcinoma That Has Progressed After Prior VEGFR Tyrosine Kinase Inhibitor Therapy


Condition: Advanced Renal Cell Carcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03339219

Sponsor: Takeda

Phase: Phase 2

Eligibility:

  • Age: minimum 20 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • Male or female Japanese patients 20 years of age or older on the day of consent.
  • Documented histological or cytological diagnosis of RCC with a clear-cell component.
  • Measurable disease per RECIST 1.1 as determined by the investigator.
  • Must have received at least one VEGFR-targeting TKI (eg, sorafenib, sunitinib, axitinib, pazopanib or tivozanib).
  • For the most recently received VEGFR-targeting TKI the following criteria must apply:
  • Must have radiographically progressed during treatment, or been treated for at least 4 weeks and radiographically progressed within 6 months after the last dose. Radiographic progression is defined as unequivocal progression of existing tumor lesions or developing new tumor lesions as assessed by the investigator on computerized tomography (CT) or magnetic resonance imaging (MRI) scans.
  • The last dose must have been within 6 months before the first day of study drug administration (Week 1 Day 1).
  • Recovery to baseline or ≤Grade 1 Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy.
  • Karnofsky Performance Status (KPS) score of ≥70%.
  • Adequate organ and marrow function at Screening.

Exclusion Criteria:

  • Prior treatment with everolimus, or any other specific or selective target of rapamycin complex 1 /phosphoinositide 3-kinase/AKT inhibitor (eg, temsirolimus), or cabozantinib.
  • Receipt of any type of small-molecule kinase inhibitor (including investigational kinase inhibitor) within 14 days before Week 1 Day 1.
  • Receipt of any type of anticancer antibody (including investigational antibody) within 28 days before Week 1 Day 1.
  • Radiation therapy for bone metastasis within 14 days, and/or any other external radiation therapy within 28 days before Week 1 Day 1. Systemic treatment with radionuclides within 42 days before Week 1 Day 1. Patients with clinically relevant ongoing complications from prior radiation therapy are not eligible.

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

A Phase 3, Randomized, Open-Label Study of Nivolumab Combined With Cabozantinib Versus Sunitinib in Participants With Previously Untreated Advanced or Metastatic Renal Cell Carcinoma


Condition: Renal Cell Carcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03141177

Sponsor: Bristol-Myers Squibb

Phase: Phase 3

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • Histological confirmation of RCC with a clear-cell component, including participants who may also have sarcomatoid features
  • Advanced (not amenable to curative surgery or radiation therapy) or metastatic (AJCC Stage IV) RCC
  • No prior systemic therapy for RCC with the following exception: i) One prior adjuvant or neoadjuvant therapy for completely resectable RCC if such therapy did not include an agent that targets VEGF or VEGF receptors and if recurrence occurred at least 6 months after the last dose of adjuvant or neoadjuvant therapy Exclusion Criteria:
  • Any active CNS metastases
  • Any active, known or suspected autoimmune disease
  • Any condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization
  • Participants who have received a live/attenuated vaccine within 30 days of first treatment Other protocol defined inclusion/

Exclusion Criteria:

  • Any active CNS metastases
  • Any active, known or suspected autoimmune disease
  • Any condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization
  • Participants who have received a live/attenuated vaccine within 30 days of first treatment Other protocol defined inclusion/exclusion criteria could apply

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

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


Condition: Metastatic Renal Cell Carcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03149822

Sponsor: University of Colorado, Denver

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.
  • Note: Subjects with stable, treated hypothyroidism or adrenal insufficiency may qualify for the study 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 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.

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

A Randomized, Double-Blind, Placebo-Controlled Phase 2 Clinical Trial Comparing CB-839 in Combination With Cabozantinib (CB-Cabo) vs. Placebo With Cabozantinib (Pbo-Cabo) in Patients With Advanced or Metastatic Renal Cell Carcinoma (RCC)


Condition: Advanced Renal Cell Carcinoma, Metastatic Renal Cell Carcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03428217

Sponsor: Calithera Biosciences, Inc

Phase: Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  1. Documented histological or cytological diagnosis of renal cell carcinoma with a clear-cell component
  2. Adult patients
  3. Karnofsky Performance Score (KPS) ≥ 70%
  4. Measurable Disease per RECIST 1.1
  5. 1-2 lines of prior therapy for advanced or metastatic RCC including one anti-angiogenic therapy (any VEGF pathway-targeted agent used either as monotherapy or as a component of a combination regimen) OR the combination regimen of nivolumab + ipilimumab
  6. Adequate hepatic, renal, cardiac and hematologic function

Exclusion Criteria:

  1. Prior treatment with cabozantinib (or other MET inhibitor) or CB-839
  2. Receipt of other anticancer therapy within 2-6 weeks, depending on the treatment
  3. Untreated or active brain metastases or central nervous system cancer, as defined per protocol
  4. Prior gastric surgery, small bowel resection, or other conditions that may impede adequate absorption of oral study drug
  5. Known active infection with HIV, Hepatitis B or C virus
  6. Inability to discontinue proton-pump-inhibitor use before randomization
  7. Patients who are pregnant or lactating

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

Cabosun Ii: Cabozantinib Versus Sunitinib for Metastatic Variant Histology Renal Cell Carcinoma


Condition: Malignant Neoplasms of Urinary Tract, Renal Cell Carcinoma, Chromophobe Renal Cell Carcinoma, Metastatic Renal Cell Carcinoma, Papillary Renal Cell Carcinoma, Renal Cell Carcinoma Associated With Xp11.2 Translocations/TFE3 Gene Fusions, Sarcomatoid Renal Cell Carcinoma, Stage IV Renal Cell Cancer AJCC v8, Unclassified Renal Cell Carcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03541902

Sponsor: M.D. Anderson Cancer Center

Phase: Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • 1. The subject has a histologic or cytologic diagnosis of a variant histology renal cell carcinoma including papillary, chromophobe, Xp.11 translocation, undifferentiated, or unclassified which is treatment naïve or has previously been treated with one systemic treatment line not containing any vascular endothelial growth factor antibody or vascular endothelial growth factor receptor tyrosine kinase inhibitors. The patient may have received treatment with immune checkpoint therapy including nivolumab as a single agent or nivolumab plus ipilimumab in combination. Previous treatment with mammalian target of rapamycin agents such as temsirolimus or everolimus is acceptable. 2. Measurable disease per RECIST v1.1 as determined by the investigator. 3. The subject has had an assessment of all known disease sites eg, by computerized tomography (CT) scan, magnetic resonance imaging (MRI), bone scan as appropriate, within 28 days before the first dose of cabozantinib or sunitinib. 4. The subject is >/=18 years old on the day of consent; 5. The subject has an Eastern Cooperative Oncology Group (ECOG) performance status of /= 1500/mm^3 without colony stimulating factor support; b.White blood cell count >/= 2500/mm^3 (>/= 2.5 GI/L). c.Platelets >/=100,000/mm^3; d.Hemoglobin >/= 9 g/dL; e. Bilirubin /= 2.8 g/dl g.Serum creatinine /= 30 mL/min (>/= 0.5 mL/sec) using the Cockcroft-Gault equation: Males: (140
  • age) x weight (kg)/(serum creatinine [mg/dL] × 72) Females: [(140
  • age) x weight (kg)/(serum creatinine [mg/dL] × 72)] × 0.85 h.Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP)

Exclusion Criteria:

  1. The subject has a variant histology that includes renal medullary carcinoma or collecting duct renal cell carcinoma. Any clear cell component in the tumor will lead to exclusion.
  2. The subject has received any previous anti-angiogenic agent. Prior treatment with cabozantinib.
  3. Radiation therapy for bone metastasis within 2 weeks, any other external radiation therapy within 4 weeks before the first dose of study treatment. Systemic treatment with radionuclides within 6 weeks before the first dose of study treatment. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible;
  4. The subject has received any other type of investigational agent within 28 days before the first dose of study treatment;
  5. Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks before the first dose of study treatment. Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of the start of study treatment;
  6. Concomitant anticoagulation with oral anticoagulants (eg, warfarin, direct thrombin and Factor Xa inhibitors) or platelet inhibitors (eg, clopidogrel). Allowed anticoagulants are the following: o Low-dose aspirin for cardioprotection (per local applicable guidelines) is permitted. o Low-dose low molecular weight heparins (LMWH) are permitted. Anticoagulation with therapeutic doses of LMWH is allowed in subjects without known brain metastases who are on a stable dose of LMWH for at least 6 weeks before first dose of study treatment, and who have had no clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor.
  7. The subject has prothrombin time (PT)/INR or partial thromboplastin time (PTT) tes>/=1.3 X the laboratory ULN within 7 days before the first dose of study treatment.
  8. The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions: Cardiovascular disorders: a.Congestive heart failure New York Heart Association Class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias. b.Uncontrolled hypertension defined as sustained blood pressure (BP) > 150 mm Hg systolic or > 100 mm Hg diastolic despite optimal antihypertensive treatment. c.Stroke (including transient ischemic attack [TIA]), myocardial infarction (MI), or other ischemic event, or thromboembolic event (eg, deep venous thrombosis, pulmonary embolism) within 6 months before first dose.
  9. Continuation of 8:Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation: The subject has evidence of tumor invading the GI tract, active peptic ulcer disease, inflammatory bowel disease (eg, Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis, acute obstruction of the pancreatic duct or common bile duct, or gastric outlet obstruction. Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess within 6 months before first dose.
  10. Continuation of 8: Clinically significant hematuria, hematemesis, or hemoptysis of > 0.5 teaspoon (2.5 ml) of red blood, or other history of significant bleeding (eg, pulmonary hemorrhage) within 12 weeks before first dose. Cavitating pulmonary lesion(s) or known endotracheal or endobronchial disease manifestation. Lesions invading or encasing any major blood vessels. Other clinically significant disorders that would preclude safe study participation. Serious non-healing wound/ulcer/bone fracture. Uncompensated/symptomatic hypothyroidism. Moderate to severe hepatic impairment (Child-Pugh B or C).
  11. Major surgery (eg, GI surgery, removal or biopsy of brain metastasis) within 8 weeks before first dose of study treatment. Complete wound healing from major surgery must have occurred 1 month before first dose and from minor surgery (eg, simple excision, tooth extraction) at least 10 days before first dose. Subjects with clinically relevant ongoing complications from prior surgery are not eligible.
  12. Corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms per electrocardiogram (ECG) within 28 days before first dose of study treatment
  13. Pregnant or lactating females.
  14. Inability to swallow tablets
  15. Previously identified allergy or hypersensitivity to components of the study treatment formulations.
  16. Diagnosis of another malignancy within 2 years before first dose of study treatment, except for superficial skin cancers, or localized, low grade tumors deemed cured and not treated with systemic therapy. Patients with Gleason 6 (3+3) prostate cancer with previous treatment or on active surveillance may also be allowed on protocol.
  17. The subject requires chronic concomitant treatment with strong CYP3A4 inducers (eg, dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, and St. John's Wort).

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

Prospective Non Interventional Study of Cabozantinib Tablets in Adults With Advanced Renal Cell Carcinoma Following Prior Vascular Endothelial Growth Factor (VEGF)-Targeted Therapy


Condition: Renal Cell Carcinoma

Study Type: Observational

Clinical Trials Identifier NCT 8-digits: NCT03419572

Sponsor: Ipsen

Phase:

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • Age ≥18 years old
  • Has a diagnosis of advanced RCC
  • Has received at least one prior VEGF-targeted therapy
  • For whom the treating physician has decided to start treatment with cabozantinib tablets prior to inclusion
  • No previous exposure to cabozantinib prior to inclusion
  • Not concurrently involved in an interventional study
  • Consents to participate in this noninterventional study Exclusion Criteria:
  • There are no

Exclusion Criteria:

  • There are no exclusion criteria for this study.

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

A Phase II Safety Trial of Nivolumab in Patients With Metastatic Renal Cell Carcinoma Who Have Progresses During or After Prior Systemic Anti-angiogenic Regimen


Condition: Metastatic Renal Cell Carcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03013335

Sponsor: UNICANCER

Phase: Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  1. Adult men and women ≥ 18 years.
  2. Patients with a histologically confirmed Renal Cell Carcinoma with a clear-cell component
  3. Patients with metastatic (AJCC stage IV) Renal Cell Carcinoma, with at least one measurable lesion by CT Scan or MRI according to RECIST 1.1 or with clinically apparent disease that can be reliably monitored by the investigator.
  4. Patients having received at least one prior systemic anti-angiogenic treatment including but not limited to: sunitinib, sorafenib, pazopanib, axitinib, and bevacizumab, in the advanced or metastatic setting. Prior cytokine therapies (e.g. IL-2, IFN-α), vaccine therapy or treatment with cytotoxics are allowed. Patients intolerant to prior systemic anti-angiogenic treatment can also be eligible (except hypersensitivity to other monoclonal antibodies). A maximum of 25% of patients with more than 2 prior systemic treatments will be recruited per sites.
  5. Patients with Eastern Cooperative Oncology Group (ECOG) performance status ≤
  6. (Appendix 3)
  7. Favorable, intermediate or poor risk group patients measured by the IMDC model (Appendix 2).
  8. Patients with brain metastases will be eligible if they are: asymptomatic, without edema, not on corticosteroids, not be eligible for radiation therapy/surgery and not receiving active treatments.
  9. Patients who have progressed following radiation therapy. Palliative, focal radiation therapy, and immunosuppressive doses of systemic corticosteroids, except replacement organotherapy (hydrocortisone and fludrocortisone), must be discontinued at least 2 weeks prior to the first nivolumab administration.
  10. Potentially reproductive patients must agree to use an effective contraceptive method or practice adequate methods of birth control or practice complete abstinence while on treatment, and for at least 31 weeks (≈ 7 months) for males and 23 weeks (≈ 5 months) for females after the last dose of study drug. Azoospermic males and women of childbearing potential who are continuously not heterosexually active are exempt from contraceptive requirements.
  11. Women of childbearing potential must have a negative serum pregnancy test done within 24 hours prior to the first dosing.
  12. Women who are breastfeeding should discontinue nursing prior to the first dose of study drug and until 6 months after the last dose.
  13. Provision of signed and dated, written informed consent prior to any study specific procedures, sampling and analyses.
  14. Patients with social insurance coverage.

Exclusion Criteria:

  • 1. Patients with any active autoimmune disease or a history of known autoimmune disease (Patients with type I diabetes mellitus, residual hypothyroidism due to an autoimmune condition requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are however eligible for this trial). 2. Patients with uncontrolled adrenal insufficiency. 3. Patients with known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS). 4. Patients with positive tests for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV RNA) indicating active or chronic infection. 5. Patients having received prior therapy with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody (or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways). 6. Patients having received any non-oncology vaccine therapy used for prevention of infectious diseases including seasonal (influenza) vaccinations within 4 weeks of the first dose of study drug. 7. Patients receiving anti-cancer therapies must be discontinued at least 2 weeks prior to administration of study drug. Palliative, focal radiation therapy, and immunosuppressive doses of systemic corticosteroids, except replacement organotherapy (hydrocortisone and fludrocortisone), must be discontinued at least 2 weeks before administration of study drug. All toxicities attributed to prior anti-cancer therapy other than alopecia must have resolved to grade 1 (NCI CTCAE version 4) or baseline before administration of study drug. 8. Patients with other prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix or breast. 9. Patients with altered hematopoietic or organ function, as indicated by the following criteria (assessed within -14 days prior the first dosing):
  • WBC < 2000/µL
  • Polynuclear neutrophils < 1.5 x 109/L
  • Platelets < 100 x 109/L
  • Hemoglobin < 8.0 g/mL
  • ALAT/ASAT > 3.0 x ULN in the absence of liver metastases or > 5x ULN in the presence of liver metastases
  • Bilirubin > 1.5 x ULN (except Gilbert Syndrome : < 3.0 mg/dL)
  • Creatinine clearance ≤ 40 mL/min (measured or calculated by Cockroft and Gault formula) or serum creatinine > 2.0 x ULN 10. Patients with a history of hypersensitivity to other monoclonal antibodies or to the active or inactive excipients of study drug. 11. Known drug or alcohol abuse. 12. Known or underlying medical condition (e.g., a condition associated with diarrhea or acute diverticulitis) that, in the investigator's opinion, would make the administration of study drug hazardous to the patient or obscure the interpretation of toxicity determination or adverse events. 13. History of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant, precluding informed consent, or interfering with compliance of oral drug intake. 14. Unwillingness to give written informed consent, unwillingness to participate, or inability to comply with the protocol for the duration of the study. 15. Individuals deprived of liberty or placed under the authority of a tutor. 16. Treatment with any other investigational agent, or participation in another clinical trial within 28 days prior to enrolment and during the treatment period

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

A Randomized Phase II Trial of Sunitinib/Gemcitabine or Sunitinib in Advanced Renal Cell Carcinoma With Sarcomatoid Features


Condition: Kidney Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT01164228

Sponsor: Eastern Cooperative Oncology Group

Phase: Phase 2

Eligibility:

  • Age: minimum 18 Years maximum 120 Years
  • Gender: All

Disease Characteristics:

  • Histologically confirmed* renal cell carcinoma
  • Disease of any subtype allowed
  • Disease must have sarcomatoid features NOTE: *Patients must have a paraffin-embedded tumor specimen from the kidney or metastatic site available for central review and confirmation of tumor histology
  • No collecting duct or medullary carcinoma
  • Measurable advanced disease that is not resectable by surgery
  • Patients with resected or radiated brain metastases or those treated with stereotactic radiation therapy are eligible, provided they have been off steroids for at least 2 weeks

Patient Characteristics:

  • ECOG performance status 0-2
  • AGC ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Hemoglobin ≥ 9.0 g/dL (transfusions allowed)
  • Serum creatinine clearance ≥ 30 mL/min
  • SGOT and SGPT ≤ 2.5 times ULN (≤ 5 times ULN in the presence of liver metastases)
  • Total bilirubin ≤ 1.5 times ULN
  • Baseline QTc interval < 500 msec on EKG
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception before and during study treatment
  • Able to swallow pills
  • No history of stroke within the past 6 months
  • No clinically significant cardiovascular disease, defined as one of the following:
  • Uncontrolled hypertension (BP > 150/100 mm Hg at the time of enrollment)
  • Patients with hypertension and BP ≤ 150/100 mm Hg on stable antihypertensive regimen are eligible
  • History of myocardial infarction or unstable angina within the past 24 weeks
  • NYHA class II-IV congestive heart failure, serious cardiac arrhythmia requiring medication, or unstable angina pectoris
  • Peripheral vascular disease ≥ grade II
  • No ongoing ventricular cardiac dysrhythmias ≥ grade 2 as assessed by NCI CTCAE version 4
  • No patients with a history of serious ventricular arrhythmia (ventricular tachycardia or ventricular fibrillation > 3 beats in a row)
  • No patients with ongoing atrial fibrillation
  • No pre-existing thyroid abnormality with thyroid-stimulating hormone that cannot be maintained at less than or within the normal range with medication
  • No serious concurrent illness or active infection that would jeopardize the ability of the patient to receive study treatment
  • No known HIV
  • Patients with a history of prior malignancy are eligible provided they were treated with curative intent and have been disease free for the time period considered appropriate to not interfere with the outcome of this study

Prior Concurrent Therapy:

  • No prior systemic therapy for metastatic disease
  • Patients who were randomized to placebo on an adjuvant study are eligible
  • More than 2 weeks since prior radiotherapy and recovered
  • Previously irradiated lesions must not be the sole site of disease
  • More than 2 weeks since prior and no concurrent ketoconazole, dexamethasone, dysrhythmic drugs (terfenadine, quinidine, procainamide, sotalol, probucol, bepridil, indapamide, or flecainide), haloperidol, risperidone, rifampin, grapefruit, or grapefruit juice
  • Topical and inhaled steroids are allowed

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

Clinical Registry Describing Treatment Reality and Therapy Modality of Patients With Metastatic or Locally Advanced Renal Cell Carcinoma Requiring Therapy


Condition: Renal Cell Carcinoma

Study Type: Observational [Patient Registry]

Clinical Trials Identifier NCT 8-digits: NCT00610012

Sponsor: iOMEDICO AG

Phase:

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • Patients with metastatic or locally advanced Renal Cell Carcinoma requiring therapy
  • Start of first palliative therapy within 1 year before enrollment of patient to registry; since enrollment of 1000 Patients: start of first palliative therapy within 4 weeks before enrollment

Exclusion Criteria:

  1. -

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

A Phase II Trial of Everolimus and Bevacizumab in Advanced Non-Clear Cell Renal Cell Carcinoma (RCC)


Condition: Renal Cell Carcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT01399918

Sponsor: Memorial Sloan Kettering Cancer Center

Phase: Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • Advanced renal cell carcinoma of non-clear cell histology, histologically with papillary features confirmed by MSKCC pathology. Availability of additional tissue for correlative studies is NOT in inclusion requirement.
  • Evidence of unidimensionally measurable disease per RECIST 1.1 (Eisenhauer, Therasse et al. 2009). Resolution of all acute toxic effects of prior radiotherapy or surgical procedures to NCI CTCAE Version 4.0 grade ≤1.
  • Adequate organ function as defined by the following criteria:
  • Absolute neutrophil count (ANC) ≥1,500/μL
  • Platelets ≥100,000/μL
  • Hemoglobin ≥9.0 g/dL
  • Serum calcium ≤12.0 mg/dL
  • Serum creatinine ≤1.5 x ULN
  • Total serum bilirubin ≤2.0 x ULN
  • Serum aspartate transaminase (AST; serum glutamic oxaloacetic transaminase [SGOT]) and serum alanine transaminase (ALT; serum glutamic pyruvic transaminase [SGPT]) ≤2.5 x local laboratory upper limit of normal (ULN), or AST and ALT ≤5 x ULN if liver function abnormalities are due to underlying malignancy
  • INR ≤1.5. (Anticoagulation is allowed if target INR ≤ 1.5 on a stable dose for >2 weeks at time of study entry.)
  • Fasting serum cholesterol ≤300 mg/dL OR ≤7.75 mmol/L AND fasting triglycerides ≤ 2.5 x ULN. NOTE: In case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication. Karnofsky performance status ≥ 70 %.
  • 18 years of age or older.
  • Ability to swallow oral medication.
  • Signed and dated informed consent document indicating that the subject (or legally acceptable representative) has been informed of all pertinent aspects of the trial prior to undergoing study screening procedures.
  • Subject's willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.

Exclusion Criteria:

  • Patients who have received prior systemic therapy for their RCC with VEGF pathway inhibitor (such as sunitinib, sorafenib, and bevacizumab) or with mTOR inhibitors (such as sirolimus, temsirolimus, everolimus, or deforolimus).
  • Patients within 28 days post major surgery (e.g., intra-thoracic, intra-abdominal or intra-pelvic), open biopsy, or significant traumatic injury to avoid wound healing complications. Minor procedures and percutaneous biopsies or placement of vascular access device without complications require 48 hours prior to study entry.
  • Patients who had radiation therapy within 28 days prior to start of study treatment (palliative radiotherapy to bone lesions allowed if completed 2 weeks prior to study treatment start). Patients with evidence or history of central nervous system (CNS) metastases or spinal cord compression, unless prior treatment with surgery or radiotherapy AND no progression of CNS disease within 6 months prior to enrollment.
  • Patients with a history of abdominal fistula, gastrointestinal perforation, or intraabdominal abscess within 6 months prior to study enrollment.
  • Patients with proteinuria on screening urinalysis confirmed to be >1g /24h by 24 hour urine collection.
  • Patients with inadequately controlled hypertension (defined as a blood pressure of > 150 mmHg systolic and/or > 100 mmHg diastolic on medication), or any prior history of hypertensive crisis or hypertensive encephalopathy. Patients receiving chronic systemic treatment with corticosteroids (dose of ≥ 10 mg/day methylprednisone equivalent) or another immunosuppressive agent. Inhaled and topical steroids are acceptable.
  • Patients with a known history of HIV seropositivity.
  • Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
  • unstable angina pectoris (at any time), symptomatic congestive heart failure (NYHA III, IV) (at any time), serious uncontrolled cardiac arrhythmia (at any time), myocardial infarction, cerebrovascular accidents, or symptomatic left ventricular dysfunction ≤ 6 months prior to first study treatment
  • active bleeding diathesis
  • known severely impaired lung function defined as spirometry and DLCO ≤ 50% of normal and oxygen saturation at rest ≤ 88% on room air.
  • symptomatic intrinsic lung disease requiring oxygen supplementation at baseline
  • Uncontrolled diabetes mellitus as defined by HbA1c >8% despite adequate therapy. Patients with a known history of impaired fasting glucose or diabetes mellitus (DM) may be included, however blood glucose and antidiabetic treatment must be monitored closely throughout the trial and adjusted as necessary
  • any active (acute or chronic) or uncontrolled infection/disorders that impair the ability to evaluate the patient or for the patient to complete the study
  • liver disease such as cirrhosis decompensated liver disease or active and chronic hepatitis (i.e. quantifiable HBV-DNA and/or positive HBsAg, quantifiable HCV-RNA).
  • Patients who have a history of another primary malignancy and are off treatment for ≤ 3 years, with the exception of non-melanoma skin cancer and carcinoma in situ of the uterine cervix.
  • Female patients who are pregnant or breast feeding
  • Women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, must use highly effective methods of contraception during the study and 8 weeks after. Highly effective contraception methods include combination of any two of the following: 1. Use of oral, injected or implanted hormonal methods of contraception or; 2. Placement of an intrauterine device (IUD) or intrauterine system (IUS); 3. Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/ vaginal suppository; 4. Total abstinence or; 5. Male/female sterilization
  • Women are considered post-menopausal and not of child-bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks prior to randomization. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child-bearing potential.
  • Male patients whose sexual partner(s) are WOCBP who are not willing to use adequate contraception, during the study and for 8 weeks after the end of treatment
  • Patients who are using other investigational agents or who had received investigational drugs ≤ 4 weeks prior to study treatment start.
  • Patients who have received attenuated live vaccines within one week of study entry. Examples of live vaccines include intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella and TY21a typhoid vaccines. Known intolerance or hypersensitivity to Everolimus or other rapamycin analogs (e.g. sirolimus, temsirolimus).
  • Known impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral Everolimus.
  • Patients with a history of non-compliance to medical regimens or who are considered potentially unreliable or will not be able to complete the entire study

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

An Open-label, Multi-center Phase 2 Study to Evaluate Everolimus as Monotherapy Treatment for Patients With Metastatic Recurrent and/or Unresectable Renal Cell Carcinoma (EVERMORE).


Condition: Renal Cell Carcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT01206764

Sponsor: Novartis Pharmaceuticals

Phase: Phase 4

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • Patients may be entered in the study only if they meet all of the following criteria:
  • Age ≥18 years old;
  • Patients with advanced renal cell carcinoma with confirmed clear or non-clear cell histology, with or without nephrectomy, and with any MSKCC prognosis;
  • Prior cytokine therapy is permitted;
  • Patients with at least one measurable lesion at baseline as per the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. If skin lesions are reported as target lesions, they must be documented (at baseline and at every physical exam) using color photography and a measuring device (such as a caliper) in clear focus to allow the size of the lesion(s) to be determined from the photograph;
  • Life expectancy ≥3 months. Life expectancy should be judged in relation to other determining patient eligibility factors such as laboratory results, Karnofsky Performance Status, etc.;
  • Patients with a Karnofsky Performance Status ≥70%;
  • Adequate bone marrow function as shown by: absolute neutrophil count (ANC) ≥1.5 x 109/L, platelets ≥100 x 109/L, hemoglobin (Hb) >9 g/dL;
  • Adequate liver function: serum bilirubin ≤1.5 x upper limit of normal (ULN), alanine transaminase (ALT), and aspartate transaminase (AST) ≤2.5 x ULN;
  • Adequate renal function: serum creatinine ≤1.5 x ULN;
  • Females of childbearing potential must have had a negative serum or urine pregnancy test 7 days prior to the administration of the study treatment start;
  • Patients who give a written informed consent obtained according to local guidelines.

Exclusion Criteria:

  • Patients may not be entered into the study if they meet any of the following criteria:
  • Patients within 2 weeks post-minor surgery (e.g., herniorrhaphy), 4 weeks post-major surgery (e.g., intra-thoracic, intra-abdominal, or intra-pelvic) to avoid wound healing complications. Percutaneous biopsies require no waiting time prior to study entry;
  • Patients with a recent history of hemoptysis, ≥0.5 teaspoon of red blood;
  • Patients who have received prior systemic treatment for their metastatic RCC other than with cytokine therapy;
  • Patients who received prior therapy with a VEGF pathway inhibitor, such as sunitinib, sorafenib, and bevacizumab;
  • Patients who have previously received mTOR inhibitors (sirolimus, temsirolimus, everolimus, deferolimus);
  • History or clinical evidence of central nervous system (CNS) metastases. Note: Subjects who have previously-treated CNS metastases (surgery ± radiotherapy, radiosurgery, or gamma knife) and meet all 3 of the following criteria are eligible: Are asymptomatic; Have had no evidence of active CNS metastases for ≥6 months prior to enrollment and; Have no requirement for steroids or enzyme-inducing anticonvulsants (EIAC); • Clinically significant gastrointestinal abnormalities including, but not limited to: Malabsorption syndrome; Major resection of the stomach or small bowel that could affect the absorption of study drug; Active peptic ulcer disease; Inflammatory bowel disease; Ulcerative colitis, or other gastrointestinal conditions with increased risk of perforation; History of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess within 28 days prior to beginning of study treatment;
  • Patients receiving chronic systemic treatment with corticosteroids (dose of ≥10 mg/day methylprednisone equivalent) or another immune-suppressive agent. Inhaled and topical steroids are acceptable, as well as opotherapy after bilateral adrenal gland removal;
  • Patients with a known history of human immunodeficiency virus seropositivity;
  • Patients with autoimmune hepatitis;
  • Patients with an active, bleeding diathesis. Patients may use coumadin or heparin preparations;
  • Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study;
  • Patients who have a history of another primary malignancy ≤3 years, with the exception of non-melanoma skin cancer and carcinoma in situ of uterine;
  • Female patients who are pregnant or breastfeeding, or adults of reproductive potential who are not using effective birth control methods. If barrier contraceptives are being used, these must be continued throughout the study by both sexes. Oral contraceptives are not acceptable;
  • Patients who are using other investigational agents or who had received investigational drugs ≤4 weeks prior to study treatment start; Patients unwilling or unable to comply with the protocol. Other protocol-defined inclusion/exclusion may apply

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

Phase II Study of Gemcitabine and Cisplatin as Neoadjuvant Chemotherapy in Patients With High-Grade Upper Tract Urothelial Carcinoma


Condition: Urothelial Carcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT01261728

Sponsor: Memorial Sloan Kettering Cancer Center

Phase: Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • Histologically confirmed high-grade upper tract transitional cell carcinoma at MSKCC or a participating site and/or radiographically visible tumor stage T2-T4a N0/X M0 disease with positive selective urinary cytology or high-grade concomitant bladder tumor. Hydronephrosis associated with tumor on biopsy will be considered invasive by definition.
  • Medically appropriate candidate for radical nephroureterectomy or ureterectomy as per MSKCC or a participating site attending urologic oncologist
  • Karnofsky Performance Status ≥ 70%
  • Age ≥ 18 years of age
  • Required Initial Laboratory Values:
  • Absolute neutrophil count ≥ 1500 cells/mm3
  • Platelets ≥ 100,000 cells/mm3
  • Hemoglobin ≥ 9.0g/dL
  • Bilirubin ≤ 1.2
  • Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x ULN for the institution
  • Alkaline phosphatase ≤ 2.5 x ULN for the institution
  • Serum creatinine ≤ 1.3 mg/dL if male or ≤ 1.1 mg/dL if female OR calculated creatinine clearance ≥ 55 ml/min/1.73m^2 If female of childbearing potential, serum pregnancy test is negative.
  • Patients with reproductive potential must use an effective method to avoid pregnancy for the duration of the trial. ml/min/1.73m2 using the formula: CKD epi : GFR = 141 X min(Scr/κ,1)α X max(Scr/κ,1)-1.209 X 0.993Age X 1.018 [if female] X 1.159 [if black]
  • Scr is serum creatinine, k is 0.7 for females and 0.9 for males, a is -0.329 for females and -0.411 for males, min indicates the minimum of Scr/k or 1, and max indicates the maximum of Scr/k or 1.
  • If female of childbearing potential, serum pregnancy test is negative.
  • Patients with reproductive potential must use an effective method to avoid pregnancy for the duration of the trial

Exclusion Criteria:

  • Concomitant bladder urothelial carcinoma is acceptable if it is organ confined and surgically resectable.
  • Presence of carcinoma in situ (CIS)
  • Prior systemic chemotherapy (prior intravesical therapy is allowed)
  • Prior radiation therapy to the bladder
  • Evidence of NYHA functional class III or IV heart disease.
  • Serious intercurrent medical or psychiatric illness, including serious active infection.
  • Preexisting sensory grade 3 neuropathy
  • Major surgery or radiation therapy < 4 weeks of starting study treatment.
  • Concomitant use of any other investigational drugs
  • Any of the following within the 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, or pulmonary embolism.
  • Ongoing cardiac dysrhythmias of NCI CTCAE Version 4.0 grade ≥ 2.
  • Uncontrolled hypertension (>150/100 mmHg despite optimal medical therapy).
  • Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness or other active infection. Patients with HIV but no evidence of AIDS will be considered candidates.
  • Concurrent treatment on another clinical trial involving an intervention which may affect the primary endpoint. Supportive care trials or non-treatment trials, e.g. QOL, are allowed.
  • Ongoing treatment with therapeutic doses of warfarin or low molecular weight heparin (low dose warfarin up to 2 mg po daily or use of subcutaneous low molecular weight heparin for thromboembolic prophylaxis is allowed).
  • Pregnancy or breast-feeding. Patients must be surgically sterile or be postmenopausal, or must agree to use effective contraception during the period of therapy. The definition of effective contraception will be based on the judgment of the MSKCC and participating site PI. Male patients must be surgically sterile or agree to use effective contraception

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

Randomized Phase III Trial Evaluating the Importance of Nephrectomy in Patients Presenting With Metastatic Renal Cell Carcinoma Treated With Sunitinib


Condition: Metastatic Renal Cell Carcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT00930033

Sponsor: Assistance Publique - Hôpitaux de Paris

Phase: Phase 3

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • age ≥ 18 years
  • ECOG Performance Status 0
  • 1
  • Biopsy (primary tumour or metastases) confirming the diagnosis of clear cell carcinoma
  • Documented metastatic disease
  • Absence of prior systemic treatment for kidney cancer including AA
  • Tumour amenable to nephrectomy (partial or total) in the opinion of the patient's urologist. Patients presenting with an inferior vena cava thrombosis can be included.
  • Patients for which the indication of Sunitinib is considered according to the recommendations rules given by national health authorities of participating countries. The prescription of Sunitinib in the circumstances of the study is considered as a standard treatment.
  • Platelets > or = 100 x 109/L, haemoglobin >or = 9 g/dl, neutrophils >or = 1.5 x 109/L;
  • Bilirubin < or = 2 mg/dL, aspartate transaminase (ASAT) and alanine transaminase (ALAT)< or = 2.5 times the upper normal limit (UNL) or < or = 5 times UNL for patients with liver metastases
  • Patients of child bearing age should use contraceptive methods
  • Patient able to follow the procedures outlined in the protocol as far as the planning of visits and examinations are concerned.
  • Life expectancy ≥ 3 months
  • Written informed consent
  • Patient without brain metastases or with radiotherapy or surgery treated brain metastases without progression into 6 weeks and non treated by corticoid
  • Patient non treated by anticoagulants excepted HBPM

Exclusion Criteria:

  • Prior systemic treatment for kidney cancer (including Anti Angiogenic)
  • Bilateral kidney cancer
  • Pregnant or breast feeding women
  • Acute coronary syndrome or episode of myocardial infarction or severe or unstable angina within the last 6 months as well as severe diabetes with severe peripheral arteriopathy or deep phlebitis not treated with low molecular weight heparin or arterial thrombosis within the last 3 months
  • Patients being treated with antivitamin K with curative intent (please note that patients being treated with low molecular weight heparin can be included)
  • Medical, general or psychiatric difficulties which, in the opinion of the Investigator, would make it inappropriate for trial entry
  • Symptomatic or untreated brain metastases (patients with brain metastases that have been treated by radiotherapy or surgery and have stable disease within 6 weeks, and are not requiring treatment with corticosteroids can be included)
  • Previous history of gastric disease or malabsorption, syndrome compromising the absorption of Sunitinib
  • Experimental treatment within the 28 days preceding inclusion
  • Other cancer within the previous 5 years (except for insitu skin carcinoma and treated localised prostate cancer with undetectable PSA)
  • Patient has received treatment with IV biphosphonate

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}
{{header-clinical-trials-navigation}}

177Lu Radiolabeled Monoclonal Antibody HuJ591-GS (177Lu-J591) in Patients With Nonprostate Metastatic Solid Tumors: A Pilot Study


Condition: Kidney Cancer, Head and Neck Cancer, Breast Cancer, Non-small Cell Lung Cancer, Colorectal Cancer, Pancreatic Cancer, Ovarian Cancer, Esophageal Cancer, Gliomas

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT00967577

Sponsor: Weill Medical College of Cornell University

Phase: Phase 1

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

Inclusion Criteria:

  • Histologically, or cytologically documented, advanced stage, malignant adult solid tumors (except prostate cancer) that are refractory to, or recurrent from, standard therapy or for which no curative standard therapy exists. This will include, but is not limited to patients with cancers of the kidney, urothelium, head and neck, breast, non-small cell lung, colorectal, pancreas, ovary, esophagus and gliomas.
  • Metastatic or recurrent solid tumor malignancy defined by abnormal CT, MRI, PET scan, CXR and/or bone scan
  • Progressive disease manifest by: Development of new lesions or an increase in size of preexisting lesions on imaging study or by physical examination.
  • Subjects must have recovered from the acute toxicities of any prior therapy, and not received chemotherapy, radiation therapy or other investigational anticancer therapeutic drug for at least 4 weeks prior to J591 administration in this trial
  • All subjects must have archived or current tissue (from a primary or metastatic focus) available for PSMA determination.
  • Subjects on bisphosphonate therapy or denosumab must be on a stable dose and must have started therapy > 4 weeks prior to protocol therapy.
  • Subjects will be informed as to the potential risk of procreation while participating on this trial and will be advised to use effective contraception during the entire study period. Females of child-bearing potential must have a negative pregnancy test.

Exclusion Criteria:

  • Use of red blood cell or platelet transfusions within 4 weeks of treatment.
  • Use of hematopoietic growth factors within 4 weeks of treatment.
  • Prior cytotoxic chemotherapy and/or radiation therapy within 4 weeks of treatment.
  • Prior radiation therapy encompassing >25% of skeleton.
  • Prior treatment with 89Strontium or 153Samarium containing compounds (e.g. Metastron®, Quadramet®)
  • Platelet count <150,000/mm3 or history of platelet count abnormality or dysfunction.
  • Absolute neutrophil count (ANC) <2,000/mm3
  • Hematocrit <30 percent or Hemoglobin < 10 g/dL
  • Abnormal coagulation profile (PT or INR, PTT) > 1.3x upper limit of normal (ULN)
  • Serum creatinine > 2x ULN
  • AST (SGOT) >2.5x ULN
  • Bilirubin (total) >1.5x ULN
  • Active serious infection
  • Active angina pectoris or NY Heart Association Class III-IV
  • ECOG Performance Status > 2
  • Deep vein thrombosis and/or pulmonary embolus within 1 month of enrollment.
  • Other serious illness(es) involving the cardiac, respiratory, CNS, renal, hepatic or hematological organ systems which might preclude completion of this study or interfere with determination of causality of any adverse effects experienced in this study.
  • Prior investigational therapy (medications or devices) within 6 weeks of treatment.
  • Known history of HIV.
  • Known leukemia or myelodysplastic syndrome
  • Prior allergic reaction to Gadolinium contrast.

View trial on ClinicalTrials.gov


{{footer-clinical-trials-navigation}}