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.

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Condition: Renal Cell Carcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02811861

Sponsor: Eisai Inc.

Phase: Phase 3

Eligibility:

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

Inclusion Criteria:

• Histological or cytological confirmation of renal cell carcinoma (RCC) with a clear-cell component
• At least 1 measurable target lesion according to Response Evaluation in Solid Tumors (RECIST) 1.1
• Karnofsky Performance Status (KPS) of ≥70
• Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP ≤150/90 mmHg at Screening and no change in antihypertensive medications within 1 week prior to Cycle 1/Day 1 (C1/D1)
• Adequate organ function per blood work

Exclusion Criteria:

• Participants who have received any systemic anticancer therapy for RCC, including anti-vascular endothelial growth factor (VEGF) therapy, or any systemic investigational anticancer agent
• Participants with central nervous system (CNS) metastases are not eligible, unless they have completed local therapy (eg, whole brain radiation therapy (WBRT), surgery or radiosurgery) and have discontinued the use of corticosteroids for this indication for at least 4 weeks before starting treatment in this study. Any signs (eg, radiologic) or symptoms of CNS metastases must be stable for at least 4 weeks before starting study treatment
• Active malignancy (except for RCC, definitively treated basal or squamous cell carcinoma of the skin, and carcinoma in-situ of the cervix or bladder) within the past 24 months. Participants with history of localized & low risk prostate cancer are allowed in the study if they were treated with curative intent and there is no prostate specific antigen (PSA) recurrence within the past 5 years
• Prior radiation therapy within 21 days prior to start of study treatment with the exception of palliative radiotherapy to bone lesions, which is allowed if completed 2 weeks prior to study treatment start
• Received a live vaccine within 30 days of planned start of study treatment
• Participants with urine protein ≥1 gram/24 hour
• Fasting total cholesterol >300 milligram per deciliter (mg/dL) (or ˃7.75 millimole per liter (mmol/L)) and/or fasting triglycerides level ˃2.5 x upper limit of normal (ULN). Note: these participants can be included after initiation or adjustment of lipid-lowering medication
• Uncontrolled diabetes as defined by fasting glucose >1.5 times the ULN. Note: these participants can be included after initiation or adjustment of glucose-lowering medication
• Prolongation of corrected QT (QTc) interval to >480 milliseconds (ms)
• Bleeding or thrombotic disorders or participants at risk for severe hemorrhage. The degree of tumor invasion/infiltration of major blood vessels should be considered because of the potential risk of severe hemorrhage associated with tumor shrinkage/necrosis following lenvatinib therapy
• Clinically significant hemoptysis or tumor bleeding within 2 weeks prior to the first dose of study drug
• Significant cardiovascular impairment within 12 months of the first dose of study drug: history of congestive heart failure greater than New York Heart Association Class II, unstable angina, myocardial infarction, cerebrovascular accident, or cardiac arrhythmia associated with hemodynamic instability. The following is also excluded: left ventricular ejection fraction below the institutional normal range as determined by multiple-gated acquisition scan or echocardiogram
• Active infection (any infection requiring systemic treatment)
• Participants known to be positive for Human Immunodeficiency Virus (HIV).
• Known active Hepatitis B (eg, Hepatitis B surface antigen (HBsAg) reactive) or Hepatitis C (eg, hepatitis C virus ribonucleic acid (HCV RNA) [qualitative] is detected)
• Known history of, or any evidence of, interstitial lung disease
• Has a history of (non-infectious) pneumonitis that required steroids, or current pneumonitis
• Participants with a diagnosis of immunodeficiency or who are receiving chronic systemic steroid therapy (doses exceeding 10 mg/day of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment. Physiologic doses of corticosteroids (up to 10 mg/day of prednisone or equivalent) may be used during the study
• Active autoimmune disease (with the exception of psoriasis) that has required systemic treatment in the past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
• Known intolerance to any of the study drugs (or any of the excipients)
• Participant has had an allogenic tissue/solid organ transplant.

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Condition: Microsatellite-instability (MSI) High Colorectal Cancer (CRC), Endometrial Cancer, Head and Neck Cancer, Hepatocellular Carcinoma (HCC), Gastric Cancer, Lung Cancer, Lymphoma, Renal Cell Carcinoma (RCC), Ovarian Cancer, Solid Tumors, UC (Urothelial Cancer), Melanoma, Bladder Cancer, Triple Negative Breast Cancer (TNBC)

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02178722

Sponsor: Incyte Corporation

Phase: Phase 1/Phase 2

Eligibility:

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

Inclusion Criteria:

• Subjects with histologically or cytologically non−small cell lung cancer (NSCLC), melanoma, transitional cell carcinoma of the genitourinary (GU) tract, renal cell cancer, triple negative breast cancer, adenocarcinoma of the endometrium or squamous cell carcinoma of the head and neck (Phase 1).
• Subjects with histologically confirmed melanoma, NSCLC, transitional cell carcinoma of the GU tract, TNBC, SCCHN, ovarian cancer, MSI high colorectal cancer (CRC), RCC, gastric cancer, HCC and DLBCL (Phase 2).
• Life expectancy > 12 weeks.
• Eastern Cooperative Oncology Group (ECOG) performance status 0
• 1.
• Presence of measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or Lugano Classification for subjects with DLBCL.
• Laboratory and medical history parameters within protocol-defined range.
• For Phase 1: Subjects who have advanced or metastatic disease as noted above that have received at least one prior therapy or have advanced or metastatic disease for which no curative treatment is available may be enrolled.
• For Phase 2 expansion cohorts: Subjects with NSCLC, melanoma (checkpoint inhibitor naïve, primary refractory melanoma, relapsed melanoma), transitional cell carcinoma of the GU tract, SCCHN, ovarian cancer, MSI high CRC, RCC, DLBCL, TNBC, gastric cancer, and HCC.
• Phase 2 expansion: NSCLC
• Subjects who have received at least 1 prior platinum-based therapy. Subjects who have a non-platinum-based regimen may be enrolled with medical monitor approval.
• Tumors with epidermal growth factor receptor mutation positive or anaplastic lymphoma kinase fusion oncogene positive treated with a tyrosine kinase inhibitor are permitted; however, subjects should have progressed on or be intolerant to the targeted therapy.
• Subjects must not have received immunotherapy with programmed death receptor-1 (PD-1) or cytotoxic T-lymphocyte antigen (CTLA-4) targeted therapy.
• Phase 2 expansion: Melanoma
• Documentation of V600E-activating BRAF mutation status.
• Prior systemic therapy requirements.
• Melanoma immune checkpoint-naïve: Subjects must not have received immunotherapy with anti-PD-1, anti-PD-L1, or anti-CTLA-4 therapy. Exception: Prior anti−CTLA-4 in the adjuvant setting would be permitted.
• Primary refractory melanoma: Subjects must have received prior treatment with anti-PD-1 or anti-PD-L1 therapy (alone or as part of a combination) in the advanced or metastatic setting and have progressive disease as their best response to treatment that is confirmed 4 weeks later.
• Relapsed melanoma: Subjects must have received prior anti−PD-1 or anti−PD-L1 therapy (alone or as part of a combination) in the advanced or metastatic setting and achieved partial response ore complete response but later have confirmed progressive disease.
• Subjects enrolling in the primary refractory or relapsed melanoma must be willing to undergo mandatory pretreatment and on-treatment biopsies.
• Ocular melanoma is excluded.
• Phase 2 expansion: Transitional cell carcinoma of the GU tract
• Metastatic or locally advanced and not amenable to curative therapy with disease progression on or after platinum-based chemotherapy or alternative therapy if platinum-based therapy is not appropriate.
• Prior PD-1 or CTLA-4 targeted therapies are excluded
• Phase 2 expansion: SCCHN
• Histologically confirmed metastatic or recurrent squamous cell carcinoma not amenable to local therapy with curative intent (surgery or radiation with or without chemotherapy). Carcinoma of the nasopharynx, salivary gland, or * *Subjects must have received at least 1 prior systemic chemotherapy regimen that must have included a platinum-based therapy.
• Prior PD-1 or CTLA-4 targeted therapies are excluded.
• Phase 2 expansion: Ovarian cancer
• Subjects with FIGO Stage Ic, Stage II, Stage III, Stage IV, recurrent, or persistent (unresectable) histologically confirmed epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube carcinoma.
• Subjects must have received a platinum-taxane-based regimen as first-line therapy.
• Prior PD-1 or CTLA-4 targeted therapies are excluded.
• Borderline, low-malignant-potential epithelial carcinoma per histopathology is excluded.
• Phase 2 expansion: Relapsed or refractory DLBCL
• Prior allogeneic stem-cell transplantation is excluded.
• Must have received > or = 1 prior treatment regimen.
• Not a candidate for curative therapy or hematopoietic stem-cell transplantation (either due to disease burden, fitness, or preference).
• Prior PD-1 or CTLA-4 targeted therapies are excluded.
• Phase 2 expansion: TNBC
• Histologically confirmed breast adenocarcinoma that is unresectable loco regional, or metastatic
• Pathologically confirmed as triple negative, source documented, defined as both of the following:
• Estrogen receptor (ER) and progesterone receptor (PgR) negative.
• Human epidermal growth factor receptor 2 (HER2) negative as per American Society of Clinical Oncology/College of American Pathologists guidelines.
• Subject must have received at least 1 prior systemic regimen for advanced or metastatic disease
• Prior PD-1 or CTLA-4 targeted therapies are excluded.
• Phase 2 expansion: RCC
• Subjects with histological or cytological confirmation of clear cell RCC.
• Not curable by surgery.
• Subjects must have received prior antiangiogenic therapy.
• Subjects must not have received prior immunotherapy with anti-PD-1, anti-PD-L1, or anti-CTLA-4 therapy.
• Phase 2 expansion: MSI high CRC
• Subjects with histological confirmation of locally advanced unresectable or metastatic MSI high CRC.
• MSI status is, respectively, determined by examining CRC tumor.
• Subjects may have received no more than 2 lines of prior therapy for advanced disease.
• Phase 2 expansion: Gastric Cancer
• Must have histologically or cytologically confirmed diagnosis of gastric or gastroesophageal junction adenocarcinoma.
• Must have progression on or after therapy containing platinum/fluoropyrimidine or refused standard therapy.
• Subjects may have received no more than 2 lines of prior therapy for advanced disease.
• Prior PD-1 or CTLA-4 targeted therapies are excluded.
• Phase 2 expansion: HCC
• Must have histologically or cytologically confirmed diagnosis of HCC (fibrolamellar and mixed hepatocellular/cholangiocarcinoma subtypes are not eligible).
• Barcelona Clinic Liver Cancer (BCLC) Stage C disease (Llovet et al 1999), or BCLC Stage B disease.
• Subjects may have received no more than 2 lines of prior therapy for the advanced disease
• Must have progressed on, refused, or were intolerant of sorafenib.
• The following are excluded: Subjects with liver transplants, clear invasion of the bile duct or main portal branch(es), or hepatorenal syndrome, or subjects who have required esophageal variceal ablation within 28 days of starting study treatment.
• Prior PD-1 or CTLA-4 targeted therapies are excluded.
• Tumor biopsies are required. If a subject has inaccessible lesions, such as in ovarian cancer, HCC, or gastric cancer, or highly vascular lesions, such as RCC, enrollment may be considered with medical monitor approval, and archived tissue may be acceptable.
• Females of child-bearing potential and males who use adequate birth control through 120 days post dose.

Exclusion Criteria:

• Subjects who participated in any other study in which receipt of an investigational study drug or device occurred within 2 weeks or 5 half-lives (whichever is longer) prior to first dose.
• Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways). Exception: Prior anti−CTLA-4 in the adjuvant setting for subjects with melanoma would be permitted.
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable.
• Has an active autoimmune disease.
• Has evidence of noninfectious pneumonitis that required steroids or current pneumonitis.
• Live vaccine use within 30 days of first dose of study medication.
• Monoamine oxidase inhibitors.

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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

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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

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Condition: Renal Cell Carcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02420821

Sponsor: Hoffmann-La Roche

Phase: Phase 3

Eligibility:

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

Inclusion Criteria:

• Definitive diagnosis of unresectable locally advanced or metastatic RCC with clear-cell histology and/or a component of sarcomatoid carcinoma, with no prior treatment in the metastatic setting
• Evaluable Memorial Sloan Kettering Cancer Center risk score
• Measurable disease, as defined by RECIST v1.1
• Karnofsky performance status greater than or equal to 70%
• Adequate hematologic and end-organ function prior to randomization Exclusion Criteria: Disease-Specific Exclusions:
• Radiotherapy for RCC within 14 days prior to treatment
• Active central nervous system disease
• Uncontrolled pleural effusion, pericardial effusion, or ascites
• Uncontrolled hypercalcemia
• Any other malignancies within 5 years except for low-risk prostate cancer or those with negligible risk of metastasis or death General Medical Exclusions:
• Life expectancy less than 12 weeks
• Participation in another experimental drug study within 4 weeks prior to treatment
• Pregnant or lactating women
• Known hypersensitivity to any component of atezolizumab or other study medication
• History of autoimmune disease except controlled, treated hypothyroidism or type I diabetes mellitus
• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis
• Positive human immunodeficiency virus test
• Active or chronic hepatitis B or C
• Severe infections within 4 weeks prior to treatment
• Exposure to oral or IV antibiotics within 2 weeks prior to treatment
• Live attenuated vaccines within 4 weeks prior to treatment (for influenza vaccination participants must agree not to receive live, attenuated influenza vaccine within 4 weeks prior to treatment, during treatment or within 5 months following the last dose)
• Significant cardiovascular disease
• Prior allogeneic stem cell or solid organ transplantation

Exclusion Criteria:

• Disease-Specific Exclusions:
• Radiotherapy for RCC within 14 days prior to treatment
• Active central nervous system disease
• Uncontrolled pleural effusion, pericardial effusion, or ascites
• Uncontrolled hypercalcemia
• Any other malignancies within 5 years except for low-risk prostate cancer or those with negligible risk of metastasis or death General Medical Exclusions:
• Life expectancy less than 12 weeks
• Participation in another experimental drug study within 4 weeks prior to treatment
• Pregnant or lactating women
• Known hypersensitivity to any component of atezolizumab or other study medication
• History of autoimmune disease except controlled, treated hypothyroidism or type I diabetes mellitus
• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis
• Positive human immunodeficiency virus test
• Active or chronic hepatitis B or C
• Severe infections within 4 weeks prior to treatment
• Exposure to oral or IV antibiotics within 2 weeks prior to treatment
• Live attenuated vaccines within 4 weeks prior to treatment (for influenza vaccination participants must agree not to receive live, attenuated influenza vaccine within 4 weeks prior to treatment, during treatment or within 5 months following the last dose)
• Significant cardiovascular disease
• Prior allogeneic stem cell or solid organ transplantation Exclusion Criteria Related to Medications:
• Prior treatment with cluster of differentiation 137 agonists, anti-cytotoxic T-lymphocyte associated protein-4, anti-programmed death (PD)-1, or anti-PD-L1 therapeutic antibody or pathway-targeting agents
• Treatment with immunostimulatory agents for non-malignant conditions within 6 weeks or immunosuppressive agents within 2 weeks prior to treatment Bevacizumab- and Sunitinib-Specific Exclusions:
• History of hypertensive crisis or hypertensive encephalopathy
• Baseline electrocardiogram showing corrected QT interval greater than 460 milliseconds

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Condition: Renal Cell Carcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03142334

Sponsor: Merck Sharp & Dohme Corp.

Phase: Phase 3

Eligibility:

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

Inclusion Criteria:

• Has histologically confirmed diagnosis of RCC with clear cell component with or without sarcomatoid features.
• Female participants of childbearing potential must be willing to use an adequate method of contraception, for the course of the study through 120 days after the last dose of study treatment.
• Male participants of childbearing potential must agree to use an adequate method of contraception, starting with the first dose of study treatment through 120 days after the last dose of study treatment.
• Has intermediate-high risk, high risk, or M1 NED RCC as defined by the following pathological tumor-node-metastasis and Fuhrman grading status: 1. Intermediate-high risk RCC: pT2, Grade 4 or sarcomatoid, N0, M0; pT3, Any Grade, N0, M0 2. High risk RCC: pT4, Any Grade N0, M0; pT, Any stage, Any Grade, N+, M0 3. M1 NED RCC participants who present not only with the primary kidney tumor but also solid, isolated, soft tissue metastases that can be completely resected at one of the following: the time of nephrectomy (synchronous) or, ≤1 year from nephrectomy (metachronous).
• Has received no prior systemic therapy for advanced RCC.
• Has undergone a partial nephroprotective or radical complete nephrectomy (and complete resection of solid, isolated, soft tissue metastatic lesion(s) in M1 NED participants) with negative surgical margins.
• Must have undergone a nephrectomy and/or metastasectomy ≥28 days prior to signing informed consent and ≤12 weeks prior to randomization.
• Must be tumor-free as assessed by the Investigator and validated by either computed tomography (CT) or magnetic resonance imaging (MRI) scan of the brain and chest, abdomen, and pelvis and a bone scan ≤28 days from randomization.
• Must have provided adequate tissue per the following: Nephrectomy only: tissue from nephrectomy (required); Synchronous M1 NED: tissue from nephrectomy (required) AND, metastasectomy tissue (if available); Metachronous M1 NED: tissue from metastasectomy (required) AND, nephrectomy tissue (if available).
• Has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 or 1.
• Has adequate organ function.

Exclusion Criteria:

• Has had major surgery, other than nephrectomy and/or resection of pre-existing metastases for M1 NED participants, within 12 weeks prior to randomization.
• Has received prior radiotherapy for RCC.
• Has pre-existing brain or bone metastatic lesions.
• Has residual thrombus post nephrectomy in the vena renalis or vena cava.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study treatment.
• Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy is allowed.
• Has a known additional malignancy that is progressing or required active treatment ≤3 years ago. Exceptions include early-stage cancers (carcinoma in situ or Stage 1) treated with curative intent, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ cervical cancer, in situ prostate cancer, or in situ breast cancer that has undergone potentially curative therapy.
• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
• Has an active infection requiring systemic therapy.
• Has a history of, or is currently on, dialysis.
• Has a known history of human immunodeficiency virus (HIV) infection.
• Has known active hepatitis B or hepatitis C virus infection.
• Has a known history of active tuberculosis (Bacillus tuberculosis).
• Has had a prior solid organ transplant.
• Has severe hypersensitivity (≥ Grade 3) to pembrolizumab and/or any of its excipients.
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the Screening visit through 120 days after the last dose of study treatment.
• Has received prior therapy with an anti-programmed cell death protein 1 (anti-PD-1), anti-programmed cell death-ligand 1 (anti-PD-L1), or anti-PD-L2 agent or with an agent directed to another co-inhibitory T-cell receptor (i.e., cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX-40, CD137 [tumor necrosis factor receptor superfamily member 9 (TNFRSF9)]) or has previously participated in a Merck pembrolizumab (MK-3475) clinical trial.
• Has received prior anticancer therapy, monoclonal antibody, chemotherapy, or an investigational agent or device within 4 weeks or 5 half-lives (whichever is longer) before first dose of study treatment or not recovered (i.e., must be ≤ Grade 1 or at Baseline) from AEs due to previously administered agents.
• Has received a live vaccine within 30 days prior to the first dose of study treatment.
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.

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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

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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

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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).

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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.

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