Bladder Cancer

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Randomized Phase II Study of Neoadjuvant Nivolumab With and Without Urelumab in Cisplatin-Ineligible or Chemotherapy-refusing Patients With Muscle-Invasive Urothelial Carcinoma of the Bladder


Condition: Urothelial Carcinoma, Bladder Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02845323

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  • Electively refusing cisplatin-based neoadjuvant chemotherapy or
  • Ineligible to receive cisplatin-based neoadjuvant chemotherapy based upon at least one of the following criteria:
  • Creatinine clearance < 60 ml/min
  • ECOG status =2
  • Grade > 2 hearing loss
  • Grade > 2 neuropathy
  • New York Heart Association Class III heart failure
  • Age ≥ 18 years old at time of consent
  • Patients must have the following laboratory values: a) Absolute neutrophil count (ANC) ≥ 1.5 K/mm3 (must be stable off any growth factor within 4 weeks of first study drug administration) b) Platelets ≥ 100 K/mm3 (transfusion to achieve this level is not permitted within 2 weeks of first study drug administration) c) Hemoglobin (Hgb) ≥ 9 g/dL d) Serum total bilirubin: ≤ 1.5 x ULN e) ALT and AST ≤ 3.0 x ULN f) Serum creatinine clearance (CrCl) ≥ 30 mL/min using the Cockcroft-Gault equation, see formula below:
  • CrCl = [140-age (years)] x weight (kg) / [72 x serum Cr (mg/dL)] (if patient is female multiply the above by 0.85)
  • Patients who give a written informed consent obtained according to local guidelines

Exclusion Criteria:

  • Patients with locally advanced unresectable or metastatic urothelial carcinoma as assessed on baseline radiographic imaging obtained within 28 days prior to study registration. The required radiographic imaging includes: a) Abdomen/Pelvis
  • CT scan b) Chest
  • chest x-ray or CT scan
  • Patients with concurrent upper urinary tract (i.e. ureter, renal pelvis) invasive urothelial carcinoma.
  • Patients with another active second malignancy other than non-melanoma skin cancers and biochemical relapsed prostate cancer
  • Patients who have received the last administration of an anti-cancer therapy including chemotherapy, immunotherapy, and monoclonal antibodies ≤ 4 weeks prior to starting study drug, or who have not recovered from the side effects of such therapy
  • Patients who have received prior therapy with immune checkpoint inhibitors (e.g. anti-PD-1, anti-PD-L1, anti-LAG3, anti-CTLA-4) or immune costimulatory molecules (e.g. anti-CD137, anti-OX40, anti-GITR) directed agents.
  • Patients who have had radiotherapy ≤ 4 weeks prior to starting study drug, or who have not recovered from radiotherapy toxicities
  • Patients who have undergone major surgery (e.g. intra-thoracic, intra-abdominal or intra-pelvic), open biopsy or significant traumatic injury ≤ 4 weeks prior to starting study drug, or patients who have had minor procedures (i.e. TURBT), percutaneous biopsies or placement of vascular access device ≤ 1 week prior to starting study drug, or who have not recovered from side effects of such procedure or injury
  • Patients with history of alcoholic or non-alcoholic steatohepatitis (NASH), auto-immune hepatitis, or previous grade 3-4 drug-related hepatitis. (Note: Patients with radiographic evidence of steatohepatitis are excluded unless a liver biopsy is obtained demonstrating no evidence of alcoholic or non-alcoholic steatohepatitis).
  • Patient with history of prior solid organ or allogeneic bone marrow transplant.
  • Patients with any of the following concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study: 1. Clinically significant cardiac diseases, including any of the following: i. History or presence of serious uncontrolled ventricular arrhythmias ii.Clinically significant resting bradycardia iii.Any of the following within 3 months prior to starting study drug: myocardial infarction (MI), severe/unstable angina, Coronary Artery Bypass Graft (CABG), Congestive Heart Failure (CHF), Cerebrovascular Accident (CVA), Transient Ischemic Attack (TIA), Pulmonary Embolism (PE) iv.Uncontrolled hypertension defined by a SBP ≥ 160 mm Hg and/or DBP ≥ 100 mm Hg, with or without anti-hypertensive medication(s) b) Cirrhosis, chronic active hepatitis or chronic persistent hepatitis c) Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory) d) Known diagnosis of any condition (i.e. post-hematopoietic or organ transplant, rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, etc.) that requires chronic immunosuppressive therapy. Usage of non-steroidal anti-inflammatory medications (NSAIDS) for the treatment of osteoarthritis and uric acid synthesis inhibitors for the treatment of gout are permitted. For questions, please consult the study chair. e) Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g. active or uncontrolled infection, uncontrolled diabetes) that could cause unacceptable safety risks or compromise compliance with the protocol
  • Pregnant or breast-feeding women
  • Women of child-bearing potential, who are biologically able to conceive, and not employing two forms of highly effective contraception. Highly effective contraception must be used throughout the trial and up to 8 weeks after the last dose of study drug (e.g. male condom with spermicidal; diaphragm with spermicide; intra-uterine device). Women of child-bearing potential, defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive months), must have a negative serum pregnancy test ≤ 14 days prior to starting study drug
  • Fertile males not willing to use contraception, as stated above
  • Patients unwilling or unable to comply with the protocol

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Phase II Study to Evaluate the Activity of Commercially Available Molecularly Matched Targeted Therapies in Selected Tumor Types Based on Genomic Alterations


Condition: Non-small Cell Lung Carcinoma, Urothelial Carcinoma, Gastrointestinal Carcinoma, Non-colon, Upper Aerodigestive Tract Carcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02795156

Sponsor: SCRI Development Innovations, LLC

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  • 1. Patients with a histologically or cytologically confirmed diagnosis of one of the following tumor types whose disease has progressed following one line of standard therapy and/or for which no standard treatment is available that has been shown to prolong survival: 1. Non-small cell lung cancer 2. Urothelial carcinoma 3. Non-colon gastrointestinal cancers (including hepatobiliary, pancreatic, and gastroesophageal tumors) 4. Upper aerodigestive tract cancers (including lip, tongue, salivary gland, gum, oral cavity, mouth, tonsils, oropharynx, nasopharynx, nasal cavity, sinus, and larynx tumors) 2. Patients must have a predefined genomic alteration that can be targeted with any of the FDA-approved targeted agents used in this study. 3. Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 4. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1. 5. Age greater than or equal to 18 years. 6. Adequate hematologic function defined as:
  • Absolute neutrophil count (ANC) ≥1500/μL
  • Platelets ≥75,000/μL 7. Adequate liver function defined as:
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x the upper limit of normal (ULN) or ≤ 5.0 X ULN if liver metastases present
  • Total bilirubin ≤1.5 x ULN (unless the patient has Grade 1 bilirubin elevation due to Gilbert's disease or a similar syndrome involving slow conjugation of bilirubin) 8. Adequate renal function defined as serum creatinine ≤1.5 x the upper limit of normal OR measured or calculated creatinine clearance ≥50 mL/min for patients with creatinine levels greater than or equal to 1.5 x the upper limit of normal. 9. Patients who are therapeutically treated with an agent such as warfarin or heparin will be allowed to receive either regorafenib or afatinib provided that their medication dose and INR/PTT are stable. Close monitoring is mandatory if the patient is receiving anticoagulants. If values are above the therapeutic range the anticoagulant doses should be modified and assessments should be repeated until stable. 10. Male patients with female partners of childbearing potential and women patients of childbearing potential are required to use two forms of acceptable contraception, including one barrier method, during their participation in the study and for 90 days following last dose of study drug(s). Male patients must also refrain from donating sperm during their participation in the study and for 90 days after the last dose of study drug. 11. Willingness and ability to comply with study and follow-up procedures. 12. Ability to understand the nature of this study and give written informed consent.

Exclusion Criteria:

  • 1. Two or more prior chemotherapy regimens in the metastatic setting. 2. Most recent chemotherapy ≤ 3 weeks and > Grade 1 chemotherapy-related side effects, with the exception of neuropathy (> grade 2 excluded) and alopecia. 3. Use of a study drug or targeted therapy ≤21 days or 5 half-lives (whichever is shorter) prior to the first dose of study treatment. For study drugs for which 5 half-lives is ≤21 days, a minimum of 10 days between termination of the study drug and administration of study treatment is required. 4. Wide field radiotherapy (including therapeutic radioisotopes such as strontium 89) administered ≤28 days or limited field radiation for palliation ≤7 days prior to starting study drug or has not recovered from side effects of such therapy. 5. Major surgical procedures ≤28 days of beginning study drug, or minor surgical procedures ≤7 days. No waiting required following port-a-cath placement. 6. Previously untreated brain metastases. Patients who have received radiation or surgery for brain metastases are eligible if therapy was completed at least 2 weeks prior to study entry and there is no evidence of central nervous system disease progression, mild neurologic symptoms, and no requirement for chronic corticosteroid therapy. Enzyme-inducing anticonvulsants are contraindicated. 7. Pregnant or lactating 8. Acute or chronic liver, renal, or pancreas disease. 9. Presence of active gastrointestinal disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of oral therapy. 10. Any of the following cardiac diseases currently or within the last 6 months:
  • Unstable angina pectoris
  • Congestive heart failure (New York Heart Association (NYHA) ≥ Grade 2
  • Acute myocardial infarction
  • Conduction abnormality not controlled with pacemaker or medication
  • Significant ventricular or supraventricular arrhythmias (patients with chronic rate-controlled atrial fibrillation in the absence of other cardiac abnormalities are eligible)
  • Valvular disease with significant compromise in cardiac function 11. Inadequately controlled hypertension. 12. Thrombotic, embolic, venous, or arterial events, such as cerebrovascular accident (including transient ischemic attacks) deep vein thrombosis or pulmonary embolism within 6 months of start of treatment. 13. Evidence or history of bleeding diathesis or coagulopathy; any haemorrhage or bleeding event ≥ NCI CTCAE Grade 3 within 4 weeks prior to start of treatment. 14. For patients receiving cabozantinib only: Do not administer cabozantinib to patients that have high risk or at high risk for severe haemorrhage. Examples include: 1. The patient has radiographic evidence of cavitating pulmonary lesion(s). 2. The patient has tumor invading or encasing any major blood vessels. 3. The patient has had hemoptysis of ≥ 0.5 teaspoon (2.5ml) of red blood within 3 months before the first dose of study treatment. 4. The patient has experienced clinically significant GI bleeding within 6 months of the first dose of study treatment. 5. The patient has experienced any other signs indicative of pulmonary hemorrhage within 3 months of the first dose of study treatment. 15. For patients receiving cabozantinib only: Do not administer cabozantinib to patients that have high risk or at high risk of perforation or fistula: 1. The patient 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. 2. Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess within 6 months before first dose. Note: Complete healing of an intra-abdominal abscess must be confirmed before first dose. 3. The patient has pre-existing fistula of head and neck area. Note: Treatment areas should be healed with no sequelae from prior radiation therapy that would predispose to fistula formation. 4. The patient has pre-existing osteonecrosis of the jaw. 16. Concomitant anticoagulation at therapeutic doses with oral anticoagulants or platelet inhibitors. [Patients receiving cabozantinib only] 17. Note: Low-dose aspirin for cardioprotection (per local applicable guidelines), low-dose warfarin (< 1 mg/day), and low dose, low molecular weight heparins (LMWH) are permitted. Anticoagulation with therapeutic doses of LMWH is allowed in subjects without radiographic evidence of brain metastasis, who are on a stable dose of LMWH for at least 12 weeks before randomization, and who have had no complications from a thromboembolic event or the anticoagulation regimen.Presence of a non-healing wound, non-healing ulcer, or bone fracture. 18. Patients with phaeochromocytoma. 19. Serious active infection at the time of treatment, or another serious underlying medical condition that would impair the ability of the patient to receive protocol treatment. 20. Known diagnosis of human immunodeficiency virus, hepatitis B, or hepatitis C. 21. Presence of other active cancers unless indolent and not requiring therapy. Patients with Stage I cancer who have received definitive local treatment and are considered unlikely to recur are eligible. All patients with previously treated in situ carcinoma are eligible, as are patients with history of non-melanoma skin cancer. 22. Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.

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Peking University First Hospital


Condition: Upper Tract Urothelial Carcinoma, Bladder Recurrence

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02740426

Sponsor: Peking University First Hospital

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  • Suspected UTUC patients without history of bladder tumor.
  • Suspected UTUC patients without synchronous bladder tumor.
  • Suspected UTUC patients without contralateral UTUCs.

Exclusion Criteria:

  • Patients with history of bladder tumor.
  • Patients with synchronous bladder tumor.
  • Patients with contralateral UTUCs.
  • Patients with advanced stage (T4).
  • Patients with other malignant tumors.

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A Phase 1/2, Open-Label, Dose-Escalation, Safety and Tolerability Study of INCB054828 in Subjects With Advanced Malignancies (FIGHT-101)


Condition: Lung Cancer, Solid Tumor, Gastric Cancer, Urothelial Cancer, Endometrial Cancer, Multiple Myeloma, Myeloproliferative Neoplasms, Breast Cancer, Cholangiocarcinoma, UC, MPN

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02393248

Sponsor: Incyte Corporation

Phase: Phase 1/Phase 2

Eligibility:

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

Inclusion Criteria:

  • 1. Male or female subjects, age 18 years or older on day of signing consent 2. Part 1: Any advanced solid tumor malignancy; Part 2: Subjects with squamous non-small cell lung cancer, cholangiocarcinoma/gastric cancer, urothelial cancer, breast/endometrial cancer, multiple myeloma, or MPNs that have a tumor or malignancy that has been evaluated and confirmed to harbor genetic alterations in FGF or FGFR genes. A subject's fibroblast growth factor (FGF) or fibroblast growth factor receptor (FGFR) alteration may be based on local or central laboratory results. Part 3: Dose finding: subjects with solid tumor malignancies who qualify for combo therapy; dose-expansion: FGF/FGFR+ subjects qualified to receive combo therapy 3. Has progressed after prior therapy and there is no further effective standard anticancer therapy available (including subject refuses or is intolerant) 4. Life expectancy > 12 weeks 5. Eastern Cooperative Oncology Group (ECOG) performance status:
  • Part 1: 0 or 1
  • Part 2 and 3: 0, 1, or 2

Exclusion Criteria:

  1. Treatment with other investigational study drug for any indication for any reason, or receipt of anticancer medications within 21 days or 5 half-lives before first dose of study drug
  2. Prior receipt of a selective FGFR inhibitor
  3. History of a calcium/phosphate homeostasis disorder
  4. History and/or current evidence of ectopic mineralization/calcification
  5. Current evidence of corneal disorder/keratopathy
  6. Has a history or presence of inadequate liver, renal, hematopoietic and/or cardiac function parameters outside protocol-defined range
  7. Prior radiotherapy within 2 weeks of study treatment

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Prospective Randomized Phase II Trial: Single Instillation Versus Long-term Prophylactic Intravesical Instillation of Pirarubicin in the Prevention of Bladder Recurrence After Nephroureterectomy for Primary Upper Tract Urothelial Carcinoma


Condition: Intravesical Instillation

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03030157

Sponsor: RenJi Hospital

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  • clinically diagnosed with upper tract urothelial carcinoma
  • have no distant metastasis
  • have an ECOG 0 to 2
  • expected to receive radical nephroureterectomy

Exclusion Criteria:

  • a prior history of bladder or synchronous bladder cancer
  • administration of neoadjuvant chemotherapy
  • the presence of severe complications
  • deny to receive cytoscopy
  • patients with advanced stage (T4)
  • patients with contralateral UTUCs

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A Multi-national, Open-label, Dose Escalation Phase I Study to Assess the Safety and Clinical Activity of Multiple Administrations of NKR-2 in Patients With Different Metastatic Tumor Types (THINK - THerapeutic Immunotherapy With NKR-2)


Condition: Acute Myeloid Leukemia/Myelodysplastic Syndrome, Multiple Myeloma (MM)

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03018405

Sponsor: Celyad (formerly named Cardio3 BioSciences)

Phase: Phase 1/Phase 2

Eligibility:

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

Inclusion Criteria:

  • are:
  • Men or women ≥ 18 years old at the time of signing the ICF,
  • Patient with a CRC, epithelial ovarian cell or fallopian tube carcinoma, urothelial carcinoma, TNBC, pancreatic cancer, AML/MDS or MM,
  • Disease must be measurable according to the corresponding guidelines,
  • Patient with an ECOG performance status 0 or 1, and AML patients with anemia resulting in an ECOG performance status of 2,
  • Patient with adequate bone marrow reserve, hepatic and renal functions.
  • Patients must have sufficient pulmonary functions with a Forced Expiratory Volume in the first second (FEV-1)/Forced Vital Capacity (FVC) ≥ 0.7 with FEV-1 ≥ 50% predicted. Main

Exclusion Criteria:

  • are:
  • Patient with a tumor metastasis in the central nervous system,
  • Patients who have received another cancer therapy within 2 weeks before the planned day for the apheresis (except hydroxyurea for AML patients),
  • Patients who receive or are planned to receive any other investigational product within the 3 weeks before the planned day for the first NKR-2 administration (except hydroxyurea for AML patients),
  • Patient is under systemic immunosuppressive drugs, unless specific cases authorized per protocol,
  • Patients who have received other cell therapies,
  • Patients who underwent major surgery within 4 weeks before the planned day for the first NKR-2 administration.
  • Patient cannot present with history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis and/or active or acute exacerbation of chronic obstructive pulmonary disease (COPD). Detailed disease specific criteria exist and can be discussed with contacts listed below.

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Prophylactic Intravesical Chemotherapy to Prevent Bladder Recurrence After Nephroureterectomy for Primary Upper Tract Urothelial Carcinoma Patients


Condition: Bladder Recurrence, Upper Tract Urothelial Carcinoma, Nephroureterectomy

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02923557

Sponsor: Peking University First Hospital

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  • Suspected UTUC patients without history of bladder tumor.
  • Suspected UTUC patients without synchronous bladder tumor.
  • Suspected UTUC patients without contralateral UTUCs.

Exclusion Criteria:

  • Patients with history of bladder tumor.
  • Patients with synchronous bladder tumor.
  • Patients with contralateral UTUCs.
  • Patients with advanced stage (T4).
  • Patients with other malignant tumors.

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A Phase 2, Two-arm Multicenter, Open-Label Study to Determine the Efficacy and the Safety of Two Different Dose Regimens of a Pan-FGFR Tyrosine Kinase Inhibitor JNJ-42756493 in Subjects With Metastatic or Surgically Unresectable Urothelial Cancer With FGFR Genomic Alterations


Condition: Urothelial Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02365597

Sponsor: Janssen Research & Development, LLC

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  • Must have histologic demonstration of metastatic or surgically unresectable urothelial cancer. Minor components of variant histology such as glandular or squamous differentiation, or evolution to more aggressive phenotypes such as sarcomatoid or micropapillary change are acceptable
  • Must have measurable disease according to the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) at baseline
  • Must have an Eastern Cooperative Oncology Group (ECOG) performance status score 0, 1, or 2
  • Must have adequate bone marrow, liver, and renal function as described in protocol
  • Negative pregnancy test (urine or serum beta human chorionic gonadotropin [b-hCG]) at Screening for women of child bearing potential who are sexually active
  • Must have shown disease progression according to RECIST, version 1.1, following prior chemotherapy for metastatic or surgically unresectable urothelial cancer. Participants who received neoadjuvant or adjuvant chemotherapy and showed disease recurrence or progression according to RECIST, version 1.1, within 12 months of the last dose are considered to have received chemotherapy in the metastatic setting. These participants will be referred to as chemo-refractory participants. (Participants who have shown disease progression according to RECIST, version 1.1 following prior treatment with anti-Programmed death-ligand 1 (anti PDL1/PD1) antibodies are also eligible) For DDI substudy
  • Disease progression following prior chemotherapy for metastatic or surgically unresectable urothelial cancer. Participants who received neoadjuvant or adjuvant chemotherapy and showed disease recurrence or progression within 12 months of the last dose are considered to have received chemotherapy in the metastatic setting.

Exclusion Criteria:

  • Received chemotherapy, targeted therapies, definitive radiotherapy, or treatment with an investigational anticancer agent within 2 weeks (in the case of nitrosoureas and mitomycin C, within 6 weeks; in the case of immunotherapy, within 4 weeks) before the first administration of study drug. Localized palliative radiation therapy (but should not include radiation to target lesions) and ongoing bisphosphonates and denosumab, are permitted
  • Has persistent phosphate level greater than upper limit of normal (ULN) during screening (within 14 days of treatment and prior to Cycle 1 Day 1) and despite medical management
  • Has a history of or current uncontrolled cardiovascular disease
  • Females who are pregnant, breast-feeding, or planning to become pregnant within 3 months after the last dose of study drug and males who plan to father a child while enrolled in this study or within 5 months after the last dose of study drug
  • Has not recovered from reversible toxicity of prior anticancer therapy (except toxicities which are not clinically significant such as alopecia, skin discoloration, or Grade 1 neuropathy)

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An Open Label Phase II Study of Tipifarnib in Patients With Previously-Treated, Advanced, HRAS Mutant Urothelial Carcinoma


Condition: Urothelial Carcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02535650

Sponsor: Samsung Medical Center

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  1. Subject is at least 20 years of age.
  2. Subject has a histologically or cytologically confirmed diagnosis of urothelial carcinoma arising from urinary bladder or upper urinary tract.
  3. Subject has been treated with platinum-based chemotherapy for advanced disease. They must have refractory or progressive disease for which there is no further curative therapy available.
  4. Subject has been treated with platinum-based chemotherapy for advanced disease. They must have refractory or progressive disease for which there is no further curative therapy available. Subject has a tumor that carries a missense HRAS mutation according to a standard methodology using Illumina HiSeqTM. (missence non-synonymous HRAS mutation and/or STK11: rs2075606 (T>C))HRAS status may have been assessed either in primary tumor tissue, recurrent or metastatic disease.
  5. Subject has consented to provide at least 10 unstained tumor slides for retrospective testing of HRAS gene tumor status.
  6. Must have a life expectancy of 3 months or more
  7. Subject has measurable disease according to RECIST(Response Evaluation Criteria in Solid Tumors ) v1.1 and has relapsed (progressive disease) or is refractory to prior therapy.
  8. At least 2 weeks since the last systemic therapy regimen prior to enrolment. Subjects must have recovered to NCI CTCAE v. 4.03 < Grade 2 from all acute toxicities (excluding Grade 2 toxicities that are not considered a safety risk by the Sponsor and Investigator) or toxicity must be deemed irreversible by the Investigator.
  9. At least 2 weeks since last radiotherapy if radiation was localized to the only site of measurable disease, unless there is documentation of disease progression of the irradiated site. Patients must have recovered from all acute toxicities from radiotherapy.
  10. ECOG(Eastern Cooperative Oncology Group ) performance status of 0 or
  11. Acceptable liver function:
  12. Bilirubin ≤ 1.5 times upper limit of normal (x ULN); does not apply to subjects with Gilbert's syndrome diagnosed as per institutional guidelines.
  13. AST (SGOT,aspartate aminotransferase ) and ALT (SGPT,Alanine aminotransferase) ≤ 3 x ULN; if liver metastases are present, then ≤ 5 x ULN is allowed.
  14. Acceptable renal function with serum creatinine ≤ 1.5 x ULN or a calculated creatinine clearance ≥ 60 mL/min using the Cockcroft-Gault or MDRD(Modification of Diet in Renal Disease ) formulas. Serum potassium with normal or ≤ CTCAE Grade 1 with or without supplementation.
  15. Acceptable hematologic status (without growth factor support or transfusion dependency):
  16. ANC(absolute neutrophil count )>1500 cells/μL.
  17. Platelet count >100,000/μL.
  18. Hemoglobin >9.0 g/dL.
  19. Female subjects must be either:
  20. Of non-child-bearing potential (surgically sterilized or at least 2 years post-menopausal); or
  21. If of child-bearing potential, subject must use an adequate method of contraception consisting of two-barrier method or one barrier method with a spermicide or intrauterine device. Both females and male subjects with female partners of child-bearing potential must agree to use an adequate method of contraception for 2 weeks prior to screening, during, and at least 4 weeks after last dose of trial medication. Female subjects must have a negative serum or urine pregnancy test within 72 hours prior to start of trial medication.
  22. Not breast feeding at any time during the study.
  23. Written and voluntary informed consent understood, signed and dated.

Exclusion Criteria:

  1. Ongoing treatment with an anticancer agent not contemplated in this protocol.
  2. Prior treatment (at least 1 full treatment cycle) with an FTase inhibitor.
  3. Any history of clinically relevant coronary artery disease or myocardial infarction within the last 3 years, New York Heart Association (NYHA) grade III or greater congestive heart failure, cerebrovascular attack within the prior year, or current serious cardiac arrhythmia requiring medication except atrial fibrillation.
  4. Known uncontrolled brain, leptomeningeal or epidural metastases (unless treated and well controlled for at least 4 weeks prior to Cycle 1 Day 1). Subjects that develop brain metastasis during the study may have their treatment interrupted to receive a course of cranial radiation and restart trial medication after a recovery period of at least 1 week. High dose corticosteroids may be employed for the management of cranial radiation but must be tapered off before resuming treatment.
  5. Non-tolerable > Grade 2 neuropathy or evidence of unstable neurological symptoms within 4 weeks of Cycle 1 Day
  6. Major surgery, other than diagnostic surgery, within 4 weeks prior to Cycle 1 Day 1, without complete recovery.
  7. Double primary cancer of other site(s), except for cured ones at the discretion of investigator
  8. Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy. Known infection with HIV, or an active infection with hepatitis B or hepatitis C.
  9. Subjects who have exhibited allergic reactions to tipifarnib, structural compounds similar to tipifarnib or to its excipients.
  10. Concomitant disease or condition that could interfere with the conduct of the study, or that would, in the opinion of the Investigator, pose an unacceptable risk to the subject in this study.
  11. The subject has legal incapacity or limited legal capacity.
  12. Dementia or significantly altered mental status that would limit the understanding or rendering of informed consent and compliance with the requirements of this protocol. Unwillingness or inability to comply with the study protocol for any reason.
  13. QTcF interval ≥ 470 msecs

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A Phase II Trial of sEphB4-HSA in Combination With Anti PD1 Antibody Pembrolizumab (MK-7435) for Metastatic Urothelial Cancer Refractory to Platinum


Condition: Stage IV Bladder Urothelial Carcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02717156

Sponsor: University of Southern California

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  • Be willing and able to provide written informed consent/assent for the trial
  • Advanced (metastatic or recurrent) pathologically proven urothelial carcinoma which is refractory to platinum based due to disease progression on a platinum containing regimen; patients progressing within 12 months of their last dose of platinum-based neoadjuvant or adjuvant chemotherapy will be considered platinum refractory
  • Have measurable disease based on RECIST 1.1
  • Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion; newly-obtained is defined as a specimen obtained for up to 6 weeks (42 days) prior to initiation of treatment on day 1; subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen only upon agreement from the Sponsor; an optional core biopsy will be requested from an accessible metastatic site after 2 cycles of treatment
  • Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
  • Absolute neutrophil count (ANC) >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • Hemoglobin >= 9 g/dL or >= 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment)
  • Measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) >= 30mL/min for subject with creatinine levels > 1.5 X institutional upper limit of normal (ULN)
  • Serum total bilirubin =< 1.5 X ULN or direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 ULN
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X ULN or =< 5 X ULN for subjects with liver metastases
  • Albumin >= 2.5 mg/dL
  • International normalized ratio (INR) or prothrombin time (PT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants
  • Activated partial thromboplastin time (aPTT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
  • Recovered to grade 1 from the effects (excluding alopecia) of any prior therapy for their malignancies
  • 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
  • Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication; subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year
  • Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy

Exclusion Criteria:

  • Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment
  • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
  • Has a known history of active TB (bacillus tuberculosis)
  • Hypersensitivity to pembrolizumab or any of its excipients
  • Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study day 1 or who has not recovered (ie, =< grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier
  • Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1 or who has not recovered (ie, =< grade 1 or at baseline) from adverse events due to a previously administered agent; Note: subjects with =< grade 2 neuropathy are an exception to this criterion and may qualify for the study; Note: if subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
  • 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 or early stage carcinoma of the cervix that has undergone potentially curative therapy or in situ cervical cancer; patients with incidental prostate cancer diagnosed at cystectomy or deemed appropriate for surveillance based on national guidelines will be allowed to enroll
  • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment; this exception does not include carcinomatous meningitis which is excluded regardless of clinical stability
  • Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs); replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc) is not considered a form of systemic treatment
  • Has known history of, or any evidence of active, non-infectious pneumonitis
  • Has an active infection requiring systemic therapy
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
  • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or sEsphB4-HSA
  • Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
  • Has known active Hepatitis B (eg, hepatitis B surface antigen [HBsAg] reactive) or Hepatitis C (eg, hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected)
  • Major systemic infection requiring antibiotics 72 hours or less prior to first dose of study drug
  • Has New York Heart Association (NYHA) class 3 or 4, myocardial infarction, acute coronary syndrome, diabetes mellitus with ketoacidosis or chronic obstructive pulmonary disease (COPD) requiring hospitalization in the preceding 6 months; or any other intercurrent medical condition that contraindicates treatment with sEphB4HSA or pembrolizumab (MK-3475) or places the patient at undue risk for treatment related complications
  • Any other condition, including mental illness or substance abuse, deemed by the investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interferes with the interpretation of the results
  • Any active bleeding in the last =< 4 weeks or have an otherwise known bleeding diathesis
  • 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 (eg, flu-mist) are live attenuated vaccines, and are not allowed

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An Open Label, Single-arm, Phase 2 Study of Neoadjuvant Pembrolizumab (MK-3475) Before Cystectomy for Patients With Muscle-invasive Urothelial Bladder Cancer.


Condition: Urothelial Bladder Carcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02736266

Sponsor: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  1. Willing and able to provide written informed consent.
  2. Ability to comply with the protocol.
  3. Age ≥ 18 years.
  4. Histopathologically confirmed transitional cell carcinoma. Patients with mixed histologies are required to have a dominant (i.e. 50% at least) transitional cell pattern.
  5. Fit and planned for cystectomy (according to local guidelines).
  6. Clinical stage T2-T4a N0 M0 disease by CT (or MRI) + PET/CT (within 4 weeks of randomization by RECIST v1.1).
  7. Residual disease after TURB (surgical opinion, cystoscopy or radiological presence).
  8. Representative formalin-fixed paraffin-embedded (FFPE) tumor specimens (blocks preferred) or at least 15 unstained slides, with an associated pathology report, for testing at the study sponsor site and determined to be evaluable for tumor PD-L1 expression prior to study enrolment; patients with fewer than 15 unstained slides available at baseline (but no fewer than 10) may be eligible following discussion with Merck representatives.
  9. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or
  10. Adequate hematologic and end-organ function tests.

Exclusion Criteria:

  • Patients taking regular oral steroids, above the allowed limit of 10mg/day methylprednisolone or analogues, for any reason. Patients must not have had steroids for 28 days prior to study entry.
  • Previously intravenous chemotherapy bladder cancer. Patients who have previously had radiotherapy or concurrent chemo-radiation would be eligible.
  • Malignancies other than UBC within 5 years prior to Cycle 1, Day 1, with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, or ductal carcinoma in situ treated surgically with curative intent) 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 < 10 ng/mL undergoing active surveillance and treatment naive).
  • Evidence of measurable nodal or metastatic disease.
  • 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).
  • Pregnant female patients. All female patients of childbearing potential with a positive pregnancy test within 2 weeks prior to the first dose of study treatment will be excluded from the study.
  • Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within 3 months prior to enrolment, unstable arrhythmias, or unstable angina.
  • Severe infections within 4 weeks prior to enrolment in the study including but not limited to hospitalization for complications of infection, bacteraemia, or severe pneumonia.
  • Major surgical procedure within 4 weeks prior to enrolment or anticipation of need for a major surgical procedure during the course of the study other than for diagnosis.
  • History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
  • Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the pembrolizumab formulation
  • History of autoimmune disease 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.
  • Patients with a history of autoimmune-related hypothyroidism, unless on a stable dose of thyroid-replacement hormone.
  • Patients with uncontrolled Type 1 diabetes mellitus
  • Uncontrolled hypercalcemia
  • Patients with prior allogeneic stem cell or solid organ transplantation.
  • History of idiopathic pulmonary fibrosis
  • Positive test for HIV.
  • Patients with active hepatitis infection
  • Patients with active tuberculosis.
  • Prior treatment with anti-programmed death-1 (PD-1), or anti-PD-L1 therapeutic antibody or pathway-targeting agents.
  • Administration of a live, attenuated vaccine within 4 weeks prior to enrolment or anticipation that such a live, attenuated vaccine will be required during the study
  • Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days prior to enrolment
  • History of severe immune-related adverse effects from anti-CTLA-4 (CTCAE Grade 3 and 4).
  • Treatment with systemic immunostimulatory agents within 4 weeks or five half-lives of the drug, whichever is shorter, prior to enrolment.

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Atezolizumab in Combination With Gemcitabine and Cisplatin As First-Line Treatment in Metastatic Urothelial Cancer: A Multicenter Randomized Phase II Study of Two Alternative Dosing Schedules


Condition: Urothelial Carcinoma, Locally Advanced, Unresectable

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03093922

Sponsor: Memorial Sloan Kettering Cancer Center

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  • Histologically confirmed urothelial carcinoma of the bladder, ureter, urethra, or renal pelvis by the enrolling institution. Patients with mixed histologies are required to have a predominant urothelial component as reviewed by the pathologist at the enrolling institution.
  • Locally advanced (T4b, any N: any T, N2-3) or metastatic (M1) disease as determined by the treating investigator.
  • Age ≥18 years
  • Life expectancy ≥ 12 weeks
  • The patient must have measurable disease according to RECIST v1.1 and must have one site amenable to biopsy that, in the opinion of the investigator and/or interventional radiologist, is likely to yield acceptable tumor sample for a core biopsy per the below pathology criteria.
  • Subject must agree to undergo two research-directed biopsies during treatment.
  • Patients must have adequate tumor tissue available for PD-L1 testing. Adequate tumor tissue is defined as:
  • For core-needle biopsy specimens, at least three cores should be submitted for evaluation if feasible. Acceptable samples include core-needle biopsies for deep tumor tissue (minimum of three cores) or excisional, incisional, punch, or forceps biopsies for cutaneous, subcutaneous, or mucosal lesions. Samples collected from fine-needle aspiration, brushing, cell pellet from pleural effusion, bone metastases without a soft tissue component, and lavage are not acceptable.
  • For pre-treatment archival tissue, representative urothelial carcinoma FFPE tumor specimens (tumor blocks or 30 unstained slides) must be provided. Patients with < 30 slides may be enrolled after discussion with the MSK Principal Investigator.
  • Primary or metastatic specimens (with the exception of bone because it is not evaluable for PD-L1 expression) may be submitted.
  • Adequate hematologic and end organ function, defined by the following laboratory results obtained within 14 days prior to the first study treatment (Cycle 1, Day 1):
  • ANC ≥ 1500 cells/uL
  • WBC counts > 2500/uL
  • Lymphocyte count ≥ 300/uL
  • Platelet count ≥ 100,000/uL; Hemoglobin ≥ 9.0 g/dL
  • Total bilirubin ≤ 1.5 x upper limit of normal (ULN) with the following exception:
  • Patients with known Gilbert disease who have total bilirubin level ≤ 3 x ULN may be enrolled.
  • AST and ALT ≤ 3.0 x ULN with the following exception: °Patients with liver metastases may enroll with AST and ALT ≤ 5 x ULN
  • Alkaline phosphatase ≤ 2.5 x ULN with the following exception: °Patients with documented liver or bone metastases may enroll with alkaline phosphatase ≤ 5 x ULN
  • Estimated glomerular filtration rate (eGFR) ≥ 50 ml/min/1.73m^2 using the CKD-EPI equation: eGFR = 141 x min(Scr/k, 1)a x max(Scr/k, 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
  • For female patients of childbearing potential and male patients with partners of childbearing potential, agreement (by patient and/or partner) to use highly effective form(s) of contraception (i.e., one that results in a low failure rate [< 1% per year] when used consistently and correctly) and to continue its use for 5 months after the last dose of atezolizumab.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
  • INR and aPTT ≤ 1.5 x ULN
  • This applies only to patients who do not receive therapeutic anticoagulation; patients receiving therapeutic anticoagulation (such as low-molecular-weight heparin or warfarin) should be on a stable dose.
  • Ability and willingness to comply with the requirements of the study protocol

Exclusion Criteria:

  • Prior chemotherapy or immunotherapy for metastatic urothelial cancer. Prior neoadjuvant or adjuvant chemotherapy with first progression > 12 months is allowed. Prior intravesical treatments such as BCG are allowed, however no BCG is allowed within 4 weeks prior to initiation of study treatment.
  • Any approved anticancer therapy, including chemotherapy, hormonal therapy, or radiotherapy, within 3 weeks prior to initiation of study treatment; however, the following are allowed:
  • Hormone-replacement therapy or oral contraceptives
  • Herbal therapy > 1 week prior to Cycle 1, Day 1. Herbal therapy intended as anticancer therapy must also be discontinued at least 1 week prior to Cycle 1, Day 1.
  • Palliative radiotherapy for bone metastases > 2 weeks prior to Cycle 1, Day 1
  • Bisphosphonate therapy for symptomatic hypercalcemia °Use of bisphosphonate therapy for other reasons (e.g., bone metastasis or osteoporosis) is allowed.
  • Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease
  • Patients with a history of or active bone marrow disorders expected to interfere with study therapy (e.g. acute leukemias, accelerated/blast-phase chronic myelogenous leukemia, chronic lymphocytic leukemia, Burkitt lymphoma, plasma cell leukemia, or non-secretory myeloma)
  • Known primary central nervous system (CNS) malignancy or symptomatic CNS metastases
  • Evaluable or measurable disease outside the CNS
  • No metastases to brain stem, midbrain, pons, medulla, cerebellum, or within 10 mm of the optic apparatus (optic nerves and chiasm)
  • No history of intracranial hemorrhage or spinal cord hemorrhage
  • No ongoing requirement for dexamethasone for CNS disease; patients on a stable dose of anticonvulsants are permitted.
  • No neurosurgical resection or brain biopsy within 28 days prior to Cycle 1, Day 1
  • Patients with asymptomatic treated CNS metastases may be enrolled, provided all the criteria listed above are met as well as the following: Radiographic demonstration of improvement upon the completion of CNS-directed therapy and no evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study No stereotactic radiation or whole-brain radiation within 28 days prior to Cycle 1, Day 1 Screening CNS radiographic study ≥ 4 weeks from completion of radiotherapy and ≥ 2 weeks from discontinuation of corticosteroids
  • Pregnancy, lactation, or breastfeeding.
  • Evidence of NYHA functional class III or IV heart disease
  • Sensory or motor peripheral neuropathy ≥ grade 2
  • Hearing loss ≥ grade 2
  • Known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
  • History or risk of autoimmune disease, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Bell's palsy, Guillain-Barré syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis. The following are exceptions to this criterion.
  • Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone may be eligible.
  • Patients with controlled Type 1 diabetes mellitus on a stable insulin regimen may be eligible.
  • Patients with celiac disease controlled on diet alone may be eligible
  • Patients with eczema, psoriasis, lichen simplex chronicus of vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided that they meet the following conditions:
  • Patients with psoriasis must have a baseline ophthalmologic exam to rule out ocular manifestations
  • Rash must cover less than 10% of body surface area (BSA)
  • Disease is well controlled at baseline and only requiring low potency topical steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%, flucinolone 0.01%, desonide 0.05%, aclometasone dipropionate 0.05%)
  • No acute exacerbations of underlying condition within the last 12 months (i.e. not requiring psoralen plus ultraviolet A radiation [PUVA], methotrexate, retinoids, biologic agents, oral calcineurin inhibitors; high potency or oral steroids)
  • History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest computed tomography (CT) scan °History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
  • 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 patient at high risk from treatment complications
  • History of HIV infection or active hepatitis B (chronic or acute) or hepatitis C infection
  • Patients with past or resolved hepatitis B infection (defined as having a negative hepatitis B surface antigen [HBsAg] test and a positive anti-HBc [antibody to hepatitis B core antigen] antibody test) are eligible.
  • Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA.
  • Active tuberculosis
  • Severe infections within 4 weeks prior to Cycle 1, Day 1, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
  • Signs or symptoms of infection within 2 weeks prior to Cycle 1, Day 1
  • Received oral or IV antibiotics within 2 weeks prior to Cycle 1, Day 1 °Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible.
  • Major surgical procedure within 28 days prior to Cycle 1, Day 1 or anticipation of need for a major surgical procedure during the course of the study
  • Administration of a live, attenuated vaccine within 4 weeks before Cycle 1, Day 1 or anticipation that such a live, attenuated vaccine will be required during the study °Influenza vaccination should be given during influenza season only (approximately October to March). Patients must not receive live, attenuated influenza vaccine (e.g., FluMist®) within 4 weeks prior to Cycle 1, Day 1 or at any time during the study.
  • Malignancies other than the disease under study within 5 years prior to Cycle 1, Day 1, with the exception of those with a negligible risk of metastasis or death and with expected curative outcome (such as but not limited to adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated surgically with curative intent, or ductal carcinoma in situ treated surgically with curative intent) or undergoing active surveillance per standard-of-care management (e.g., chronic lymphocytic leukemia Rai Stage 0, prostate cancer with Gleason score ≤ 6, and prostate-specific antigen [PSA] ≤ 10 mg/mL, etc.)
  • Prior treatment with anti-PD-1, or anti-PD-L1 therapeutic antibody or pathway-targeting agents °Patients who have received prior treatment with anti-CTLA-4 may be enrolled, provided the following requirements are met: Minimum of 12 weeks from the first dose of anti-CTLA-4 and > 6 weeks from the last dose No history of severe immune-related adverse effects from anti-CTLA-4 (NCI CTCAE Grade 3 and 4)
  • Treatment with systemic immunostimulatory agents (including but not limited to interferon [IFN]-a or interleukin [IL]-2) within 6 weeks or five half-lives of the drug (whichever is shorter) prior to Cycle 1, Day 1
  • Treatment with investigational agent within 4 weeks prior to Cycle 1, Day 1 (or within five half-lives of the investigational product, whichever is longer)
  • Treatment with systemic immunosuppressive medications (including but not limited to prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [anti-TNF] agents) within 2 weeks prior to Cycle 1, Day 1
  • Patients who have received acute, low-dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea) may be enrolled.
  • The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) is allowed.
  • History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
  • Patients with prior allogeneic bone marrow transplantation or prior solid organ transplantation

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A Phase 1/2, Open-Label, Multicenter Study to Investigate the Safety and Preliminary Efficacy of Combined Bempegaldesleukin (NKTR-214) and Pembrolizumab With or Without Chemotherapy in Patients With Locally Advanced or Metastatic Solid Tumors


Condition: Non-Small Cell Lung Cancer, Melanoma, Urothelial Carcinoma, Head and Neck Squamous Cell Carcinoma, Hepatocellular Carcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03138889

Sponsor: Nektar Therapeutics

Phase: Phase 1/Phase 2

Eligibility:

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

Inclusion Criteria:

  • Dose Optimization and Dose Expansion Inclusion Criteria:
  • Willing and able to provide written informed consent.
  • Male or female patients, age 18 years or older at the time of signing the informed consent form (ICF).
  • Life expectancy > 12 weeks from the time of enrollment as determined by the Investigator.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
  • Oxygen saturation ≥ 92% on room air for all indications.
  • Measurable disease per RECIST 1.1.
  • Patients with brain metastases are eligible if certain criteria are met.
  • Availability of fresh or archival tumor tissue
  • Patients must have a minimum of 6 months of response to any nonpalliative cancer-directed treatment Dose Optimization Inclusion Criteria (Multiple Solid Tumors):
  • Melanoma:
  • Histologically confirmed stage IV (metastatic) melanoma.
  • Non-small Cell Lung Cancer:
  • Histologically confirmed diagnosis of stage IV NSCLC
  • Must not have received systemic anti-PD-L1 therapy for metastatic disease.
  • Patients with actionable mutations with approved targeted therapy in NSCLC are excluded. Testing for mutations should be performed in accordance with standard of care.
  • Urothelial Carcinoma:
  • Histologically confirmed diagnosis of metastatic urothelial carcinoma
  • Head and Neck Squamous Cell Carcinoma (HNSCC)
  • Histologically confirmed diagnosis of metastatic HNSCC
  • Hepatocellular Carcinoma (HCC)
  • Histologically confirmed diagnosis of metastatic HCC Dose Expansion Inclusion Criteria (Non-Small Cell Lung Cancer):
  • Histologically confirmed diagnosis of stage IV NSCLC.
  • Patients must have a minimum of 6 months of response to any nonpalliative cancer-directed treatment.
  • Patients with actionable mutations with approved targeted therapy in NSCLC are excluded. Testing for mutations should be performed per standard of care.
  • Must not have received anti-cancer therapy for treatment of metastatic lung cancer
  • Must not have received prior immunotherapy Exclusion Criteria:
  • Use of an investigational agent or an investigational device within 28 days before administration of first dose of study drug(s).
  • Females who are pregnant or breastfeeding.
  • Patients who have an active autoimmune disease
  • History of allergy or hypersensitivity to study drug components
  • Evidence of clinically significant interstitial lung disease or active, noninfectious pneumonitis.
  • Prior surgery or radiotherapy within 14 days of therapy.
  • For Dose Optimization Cohort 1 only: Chemotherapy or biological therapy within 28 days of enrollment. Targeted therapy (e.g., tyrosine kinase inhibitors) within 14 days of enrollment. Patients with ongoing AEs related to prior cancer therapies will be excluded.
  • Participant's inability to adhere to or tolerate protocol or study procedures NOTE: Other protocol defined Inclusion/

Exclusion Criteria:

  • Use of an investigational agent or an investigational device within 28 days before administration of first dose of study drug(s).
  • Females who are pregnant or breastfeeding.
  • Patients who have an active autoimmune disease
  • History of allergy or hypersensitivity to study drug components
  • Evidence of clinically significant interstitial lung disease or active, noninfectious pneumonitis.
  • Prior surgery or radiotherapy within 14 days of therapy.
  • For Dose Optimization Cohort 1 only: Chemotherapy or biological therapy within 28 days of enrollment. Targeted therapy (e.g., tyrosine kinase inhibitors) within 14 days of enrollment. Patients with ongoing AEs related to prior cancer therapies will be excluded.
  • Participant's inability to adhere to or tolerate protocol or study procedures NOTE: Other protocol defined Inclusion/Exclusion criteria may apply

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Intervention of Advanced or Metastatic Urothelial Bladder Cancer by 4SCAR-T Cell Therapies


Condition: Bladder Cancer, Urothelial Carcinoma Bladder

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03185468

Sponsor: Shenzhen Geno-Immune Medical Institute

Phase: Phase 1/Phase 2

Eligibility:

  • Age: minimum 18 Years maximum 65 Years
  • Gender: All

Inclusion Criteria:

  1. Histologically or cytologically documented locally advanced or metastatic UBC (including renal pelvis, ureters, urinary bladder, and urethra)
  2. Representative tumor specimens as specified by the protocol
  3. Adequate hematologic and end organ function
  4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  5. Life expectancy greater than or equal to (>/=) 12 weeks
  6. Measurable disease, as defined by RECIST v1.1

Exclusion Criteria:

  1. Any approved anti-cancer therapy within 3 weeks prior to initiation of study treatment
  2. Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days prior to enrollment
  3. Active or untreated central nervous system (CNS) metastases as determined by computed tomography (CT) or magnetic resonance imaging (MRI) evaluation during screening and prior radiographic assessments
  4. Leptomeningeal disease
  5. Malignancies other than UBC within 5 years prior to Cycle 1, Day 1
  6. Pregnant and lactating women
  7. Significant cardiovascular disease
  8. Severe infections within 4 weeks prior to infusion
  9. Major surgical procedure other than for diagnosis within 4 weeks
  10. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins; known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation
  11. History of autoimmune disease
  12. Prior allogeneic stem cell or solid organ transplant
  13. History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
  14. Positive test for human immunodeficiency virus (HIV) and/or active hepatitis B or hepatitis C or tuberculosis

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A Phase II Open Label Single Arm Study of Adjuvant Nivolumab Following Chemo-Radiation in Localized Muscle-Invasive Bladder Cancer (NEXT)


Condition: Bladder Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03171025

Sponsor: University of Utah

Phase: Phase 2

Eligibility:

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

Inclusion Criteria:

  • Patients with muscularis propria invasion clinical stages 2 to 4 (T2-4b, N0 or N+, M0 or T1 with N+), who are not candidates for radical cystectomy.
  • Patients may have undergone partial cystectomy for removal of bladder tumor prior to chemoradiation. Patients who have M1 disease at any time prior to start of treatment are not eligible.
  • Staging is determined prior to chemoradiation
  • Patients have been evaluated by a urologic oncologist to determine eligibility for radical cystectomy prior to chemoradiation. Patients may not be candidates for radical cystectomy due to one or more reasons such as but not limited to comorbidities, age, surgical risk or patient refusal to undergo radical cystectomy. Patients who refuse to undergo radical cystectomy are not required to be evaluated by a urologic oncologist.
  • Patients must have histologically proven primary adenocarcinoma, transitional, squamous-cell, or sarcomatoid carcinoma primary of the bladder, urethra, or lower ureter.
  • Treating investigator has determined that the patients are not a candidate for radical cystectomy. Patients have been evaluated by a urologic oncologist to determine eligibility for radical cystectomy prior to chemoradiation. Patients may not be candidates for radical cystectomy due to one or more reasons such as, but not limited to, comorbidities, age, surgical risk, or patient refusal to undergo radical cystectomy.
  • Tumor tissue from the most recently resected site of disease (preferable) or from the transurethral resection that yielded the initial muscle invasive diagnosis must be provided for biomarker correlative analyses. Enrollment is permitted if adequate archived tissue is unavailable.
  • Patients must have received systemic radiosensitizing chemotherapy with definitive pelvic radiation therapy. Patients may have received partial amount of chemotherapy and radiation (both) to be eligible.
  • Platinum based chemotherapy prior to chemoradiation is permitted but not mandatory
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤2
  • Age ≥18.
  • Adequate bone marrow function White Blood Cell (WBC) > 2000/µl, neutrophils >1500/µl, Hemoglobin >9.0 g/dl.
  • Serum bilirubin and aminotransferase values less than 1.5 times the upper limit of the normal range
  • Creatinine clearance of 20 ml/min or greater as measured by the Cockroft-Gault formula
  • Able to start study treatment within 90 days of completion of chemoradiation.
  • 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.
  • Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 5 months after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
  • Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 7 months after the last dose of study therapy.
  • All toxicities attributed to prior anti-cancer therapy other than nephropathy, neuropathy, hearing loss, alopecia and fatigue must have resolved to Grade 1 (NCI CTCAE version 4.03) or baseline before administration of study drug. Subjects with toxicities attributed to prior anti-cancer therapy which are not expected to resolve and result in long lasting sequelae, such as neuropathy after platinum based therapy, are permitted to enroll.
  • Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines.

Exclusion Criteria:

  • Evidence of distant metastases or lymph node metastasis (es) that was not within the radiation field.
  • Known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin. A history of localized early stage malignancy that has undergone potentially curative therapy or is low grade and does not require active treatment is allowed.
  • Diffuse bladder carcinoma in situ (CIS) that was not able to be encompassed in a boost radiotherapy volume
  • Patients with inflammatory bowel disease
  • Patients with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
  • Patients with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 day of study drug administration. Inhaled, ocular, intraarticular, intranasal and topical steroids are permitted.
  • Patients with a known chronic immunocompromised state, HIV infection or active Hepatitis B or Hepatitis C infection.
  • Pregnancy or women of childbearing potential not willing to use contraception and men who are sexually active and not willing/able to use medically acceptable forms of contraception and breast-feeding women not willing to stop breastfeeding during study.
  • Severe active co-morbidity as determined by the investigator or principal investigator
  • Life expectancy less than 2 years

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Four Cycles of Cisplatin-Based Chemotherapy in Metastatic Urothelial Carcinoma Compared to Six Cycles: Randomized Phase III Trial - FOCUS Study -


Condition: Bladder Cancer, Ureter Cancer, Urethral Cancer, Transitional Cell Carcinoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03296306

Sponsor: Asan Medical Center

Phase: Phase 3

Eligibility:

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

Inclusion Criteria:

  1. Patients with histologically or cytologically confirmed urothelial cancer
  2. Unresectable locally advanced (T3b, N2-3), metastatic (M1), or recurrent disease
  3. Age 18 years or older
  4. Eastern Cooperative Oncology Group performance status 0-1
  5. Not progressed disease status after 2 or 4 cycles of platinum-based chemotherapy
  6. Adequate organ and bone marrow function for chemotherapy
  7. No history of radiation therapy, or radiation field within 25% of whole marrow would be allowed. If patients underwent radiation therapy in entire pelvis, they are excluded to this study. Patients should discontinue radiation therapy at least 4 weeks before enrollment, and the patients should be recovered from radiation therapy associated adverse events.
  8. Women should use contraceptive medication for 6 months after the end of the study or she would be post-menopause status. Men should consent with the contraception for 6 months after the end of the study or he would be infertile.
  9. Patients should sign a written informed consent before study entry.

Exclusion Criteria:

  1. Histologic types other than urothelial cell carcinoma should be excluded. However, urothelial cell types combined with squamous or glandular features are allowed.
  2. Patients who showed progressed disease status after 2 or 4 cycles of platinum-based chemotherapy, cannot be treated with additional chemotherapy due to adverse events, or already undertook with reduced dose of more than 50%
  3. Presence or history of CNS metastasis
  4. Prior systemic chemotherapy (But prior intravesical chemotherapy or immunotherapy was allowed, and recurrent disease after adjuvant or neoadjuvant cisplatin-based systemic chemotherapy is allowed if the last chemotherapy was administered 1 year or more before the patient enrollment)
  5. Peripheral sensory neuropathy grade 2 or worse according to NCI CTCAE
  6. History of treatment with drugs of another clinical trial within 30 days before enrollment.
  7. Concomitant severe medical, surgical, or psychiatric disease or problems which can affect the results of the clinical trial or have possibilities of unexpected medical problems caused be the drug of clinical trial
  8. History of another malignancy (but treated malignancy at least two years before enrollment were allowed, and cured non-melanoma skin cancer, any cured in-situ carcinoma, clinically insignificant localized prostate cancer, or papillary thyroid carcinoma are allowed even diagnosed less than 2 years before enrollment).
  9. Pregnant or lactating women, women of childbearing potential not employing adequate contraception

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Phase III Randomized Adjuvant Study of Pembrolizumab in Muscle Invasive and Locally Advanced Urothelial Carcinoma (AMBASSADOR) Versus Observation


Condition: Localized Renal Pelvis and Ureter Urothelial Carcinoma, Locally Advanced Bladder Urothelial Carcinoma, Locally Advanced Renal Pelvis and Ureter Urothelial Carcinoma, Locally Advanced Ureter Urothelial Carcinoma, Locally Advanced Urothelial Carcinoma, Stage II Bladder Urothelial Carcinoma AJCC v6 and v7, Stage II Renal Pelvis and Ureter Cancer AJCC v7, Stage II Ureter Cancer AJCC v7, Stage III Bladder Urothelial Carcinoma AJCC v6 and v7, Stage III Renal Pelvis and Ureter Cancer AJCC v7, Stage III Ureter Cancer AJCC v7

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT03244384

Sponsor: National Cancer Institute (NCI)

Phase: Phase 3

Eligibility:

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

Inclusion Criteria:

  • PRE-REGISTRATION ELIGIBILITY CRITERIA
  • Histologically confirmed muscle-invasive urothelial carcinoma of the bladder, urethra, upper tract, or lymph node positive (LN+) disease; variant histology allowed as long as urothelial carcinoma is predominant (any amount of squamous differentiation is allowed); any component of neuroendocrine carcinoma is excluded
  • Paraffin tissue samples obtained by transurethral resection of muscle-invasive bladder tumor, upper tract resection, or radical cystectomy/nephrectomy/ureterectomy/nephroureterectomy/cystoprostatectomy or urethrectomy must be available; this specimen submission is mandatory prior to registration as results will be used for stratification; specimens from radical/definitive surgery (radical cystectomy/nephrectomy/ureterectomy /nephroureterectomy/cystoprostatectomy and LN dissection) are preferred over transuretheral resection, if available
  • Patient must fit into one of the following three categories:
  • Patients who received neoadjuvant chemotherapy and pathologic stage at surgical resection is >= pT2 and/or N+ OR
  • Patients who are not cisplatin-eligible (according to >= 1 of the following criteria: Eastern Cooperative Oncology Group [ECOG] performance status of 2, creatinine clearance < 60 mL/min, grade >= 2 hearing loss, grade >= 2 neuropathy, or New York Heart Association class III heart failure and pathologic stage at surgical resection is >= pT3 or pN+) OR
  • Patients that decline adjuvant cisplatin-based or other systemic chemotherapy based on an informed discussion with the physician and pathologic stage at surgical resection is >= pT3 or pN+
  • The 7th edition of American Joint Committee on Cancer (AJCC) staging will be utilized; patient must have had radical cystectomy (cystoprostatectomy for men) and lymph node dissection (for bladder primary), or nephrectomy, nephroureterectomy or ureterectomy (for uppertract tumors) or urethrectomy (in addition to a radical cystectomy-either simultaneously or in the past) >= 4 weeks but =< 16 weeks prior to pre-registration; patients who have had a partial cystectomy as definitive therapy are not eligible
  • No gross cancer at the surgical margins; microscopic invasive urothelial carcinoma positive margins are allowed; carcinoma in situ (CIS) at margins is considered negative margins
  • No evidence of residual cancer or metastasis after surgery; patients with upper tract urothelial carcinoma must have a negative cystoscopy within 3 months prior to pre-registration; if the bladder has been removed a cystoscopy is not required
  • No metastatic disease (or radiologic findings "concerning" for metastatic disease) on cross-sectional imaging (according to Response Evaluation Criteria in Solid Tumors [RECIST] version [v]1.1 criteria)
  • No active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids; these include but are not limited to patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome because of the risk of recurrence or exacerbation of disease; human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible
  • No current pneumonitis or prior history of non-infectious pneumonitis that required steroids within the previous 5 years
  • Patients with vitiligo, endocrine deficiencies including type I diabetes mellitus, thyroiditis managed with replacement hormones including physiologic corticosteroids are eligible
  • Patients with rheumatoid arthritis and other arthropathies, Sjogren's syndrome and psoriasis controlled with topical medication and patients with positive serology, such as antinuclear antibodies (ANA), anti-thyroid antibodies should be evaluated for the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible
  • No known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected)
  • No live vaccine within 30 days prior to the first dose of study drug; examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guerin (BCG), and typhoid vaccine; seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist) are live attenuated vaccines and are not allowed
  • No postoperative/adjuvant systemic therapy
  • No prior treatment with any therapy on the PD-1/PD-L1 axis
  • No treatment with any other type of investigational agent =< 4 weeks before pre-registration
  • No major surgery =< 4 weeks before pre-registration
  • No radiation therapy =< 4 weeks before pre-registration
  • No neoadjuvant chemotherapy =< 4 weeks before pre-registration
  • Not currently requiring hemodialysis
  • Not pregnant and not nursing, because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown
  • ECOG performance status =< 2
  • Absolute neutrophil count (ANC) >= 1,200/mm^3
  • Leukocytes >= 3,000/ mm^3
  • Platelet count >= 75,000/mm^3
  • Hemoglobin >= 9 g/dL or >= 5.6 mmol/L
  • Total bilirubin =< 1.5 x upper limit of normal (ULN)
  • Bilirubin for patients with Gilbert's =< 3.0 x ULN
  • Calculated (calc.) creatinine clearance >= 30 mL/min (using either Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] or Cockcroft-Gault formula)
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3.0 x upper limit of normal (ULN)
  • Serum albumin >= 2.8 g/dL
  • For women of childbearing potential only: a negative urine or serum pregnancy test done =< 7 days prior to pre-registration is required
  • REGISTRATION ELIGIBILITY CRITERIA: Results of central PD-L1 testing available; Q2 Solutions will forward the PD-L1 results to the statistical center and the statistical center will notify the site that the result is available; since the results with be blinded to the site the notification from the Alliance registration/randomization office will serve as a confirmation of this

Eligibility Criteria:

  • Histologically confirmed muscle-invasive urothelial carcinoma of the bladder, urethra, upper tract, or lymph node positive (LN+) disease; variant histology allowed as long as urothelial carcinoma is predominant (any amount of squamous differentiation is allowed); any component of neuroendocrine carcinoma is excluded
  • Paraffin tissue samples obtained by transurethral resection of muscle-invasive bladder tumor, upper tract resection, or radical cystectomy/nephrectomy/ureterectomy/nephroureterectomy/cystoprostatectomy or urethrectomy must be available; this specimen submission is mandatory prior to registration as results will be used for stratification; specimens from radical/definitive surgery (radical cystectomy/nephrectomy/ureterectomy /nephroureterectomy/cystoprostatectomy and LN dissection) are preferred over transuretheral resection, if available
  • Patient must fit into one of the following three categories:
  • Patients who received neoadjuvant chemotherapy and pathologic stage at surgical resection is >= pT2 and/or N+ OR
  • Patients who are not cisplatin-eligible (according to >= 1 of the following criteria: Eastern Cooperative Oncology Group [ECOG] performance status of 2, creatinine clearance < 60 mL/min, grade >= 2 hearing loss, grade >= 2 neuropathy, or New York Heart Association class III heart failure and pathologic stage at surgical resection is >= pT3 or pN+) OR
  • Patients that decline adjuvant cisplatin-based or other systemic chemotherapy based on an informed discussion with the physician and pathologic stage at surgical resection is >= pT3 or pN+
  • The 7th edition of American Joint Committee on Cancer (AJCC) staging will be utilized; patient must have had radical cystectomy (cystoprostatectomy for men) and lymph node dissection (for bladder primary), or nephrectomy, nephroureterectomy or ureterectomy (for uppertract tumors) or urethrectomy (in addition to a radical cystectomy-either simultaneously or in the past) >= 4 weeks but =< 16 weeks prior to pre-registration; patients who have had a partial cystectomy as definitive therapy are not eligible
  • No gross cancer at the surgical margins; microscopic invasive urothelial carcinoma positive margins are allowed; carcinoma in situ (CIS) at margins is considered negative margins
  • No evidence of residual cancer or metastasis after surgery; patients with upper tract urothelial carcinoma must have a negative cystoscopy within 3 months prior to pre-registration; if the bladder has been removed a cystoscopy is not required
  • No metastatic disease (or radiologic findings "concerning" for metastatic disease) on cross-sectional imaging (according to Response Evaluation Criteria in Solid Tumors [RECIST] version [v]1.1 criteria)
  • No active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids; these include but are not limited to patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome because of the risk of recurrence or exacerbation of disease; human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible
  • No current pneumonitis or prior history of non-infectious pneumonitis that required steroids within the previous 5 years
  • Patients with vitiligo, endocrine deficiencies including type I diabetes mellitus, thyroiditis managed with replacement hormones including physiologic corticosteroids are eligible
  • Patients with rheumatoid arthritis and other arthropathies, Sjogren's syndrome and psoriasis controlled with topical medication and patients with positive serology, such as antinuclear antibodies (ANA), anti-thyroid antibodies should be evaluated for the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible
  • No known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected)
  • No live vaccine within 30 days prior to the first dose of study drug; examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guerin (BCG), and typhoid vaccine; seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist) are live attenuated vaccines and are not allowed
  • No postoperative/adjuvant systemic therapy
  • No prior treatment with any therapy on the PD-1/PD-L1 axis
  • No treatment with any other type of investigational agent =< 4 weeks before pre-registration
  • No major surgery =< 4 weeks before pre-registration
  • No radiation therapy =< 4 weeks before pre-registration
  • No neoadjuvant chemotherapy =< 4 weeks before pre-registration
  • Not currently requiring hemodialysis
  • Not pregnant and not nursing, because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown
  • ECOG performance status =< 2
  • Absolute neutrophil count (ANC) >= 1,200/mm^3
  • Leukocytes >= 3,000/ mm^3
  • Platelet count >= 75,000/mm^3
  • Hemoglobin >= 9 g/dL or >= 5.6 mmol/L
  • Total bilirubin =< 1.5 x upper limit of normal (ULN)
  • Bilirubin for patients with Gilbert's =< 3.0 x ULN
  • Calculated (calc.) creatinine clearance >= 30 mL/min (using either Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] or Cockcroft-Gault formula)
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3.0 x upper limit of normal (ULN)
  • Serum albumin >= 2.8 g/dL
  • For women of childbearing potential only: a negative urine or serum pregnancy test done =< 7 days prior to pre-registration is required
  • REGISTRATION ELIGIBILITY CRITERIA: Results of central PD-L1 testing available; Q2 Solutions will forward the PD-L1 results to the statistical center and the statistical center will notify the site that the result is available; since the results with be blinded to the site the notification from the Alliance registration/randomization office will serve as a confirmation of this eligibility criteria; after sites receive the confirmation e-mail from Alliance they can register the patient

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Electro-Phage and Colorimetric Aptamer Sensors for Clinical Staging and Monitoring of Bladder Cancer


Condition: Urinary Bladder Neoplasms

Study Type: Observational

Clinical Trials Identifier NCT 8-digits: NCT02957370

Sponsor: University of California, Irvine

Phase:

Eligibility:

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

Inclusion Criteria:

  • Patients ≥18 years old
  • Patients with diagnosed bladder cancer, undergoing transurethral resection bladder tumor (TRUBT), or under surveillance (within 2 years) for recurrent bladder cancer
  • Patients with microscopic and macroscopic hematuria
  • Willing and able to consent

Exclusion Criteria:

  • Patients <18 years old
  • Patients who are not able to give consent for study
  • Patients with urinary diversions
  • Patients who have had a recent percutaneous or endoscopic procedures for upper tract diseases such as stones or other conditions
  • Patients who have ureteral stents placed for upper urinary tract obstruction
  • Patients with recent trauma in kidney, bladder or perineal area, which may be the cause of hematuria
  • Minors will be excluded from this study because ureteral stent placement is usually performed in adult patients. Additionally, minors are treated at CHOC Hospital, and not UCIMC.
  • Women who are pregnant are excluded from this study since surgical treatments are not typically performed on pregnant women. Watchful waiting is the preferred approach for pregnant women. Furthermore, this research does not directly benefit the pregnant woman or fetus, and biomedical knowledge can be obtained using subjects who are not pregnant. Therefore, per the federal regulations, pregnant women will be excluded from this study.

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A Study of Intravesical Bacillus Calmette-Guerin (BCG) in Combination With ALT-803 in Patients With Non-Muscle Invasive Bladder Cancer


Condition: Non-muscle Invasive Bladder Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02138734

Sponsor: ImmunityBio, Inc.

Phase: Phase 1/Phase 2

Eligibility:

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

Inclusion Criteria:

  • 1. Histologic confirmation of non-muscle invasive bladder cancer of the transitional cell carcinoma high-grade subtype (mixed histology tumors allowed if transitional cell histology is predominant histology). 1. Cohort A: Histologically confirmed CIS (with or without Ta/T1 disease); Cohort B: Histologically confirmed high-grade papillary disease (Ta/T1 only). 2. Patients are eligible if the diagnostic biopsy was done within 3 months of treatment start and a cystoscopy demonstrating no resectable disease was done within 6 weeks of treatment start (residual CIS is acceptable; patients with T1 disease must undergo repeat resection if muscularis propria is not present in each biopsy sample). Patients with high-grade Ta and/or T1 disease should have complete resection before study treatment. 3. Upper tract imaging within 6 months prior to study entry must not be suspicious for upper tract malignancy. 2. Currently eligible for intravesical BCG therapy. 3. Age ≥ 18 years. 4. Performance status: ECOG performance status of 0, 1, or 2. 5. Laboratory tests performed within 21 days of treatment start: 1. Absolute neutrophil count (AGC/ANC) ≥ 1,000/µL 2. Platelets ≥ 100,000/µL [Patients may be transfused to meet this requirement] 3. Hemoglobin ≥ 8 g/dL [Patients may be transfused to meet this requirement] 4. Calculated glomerular filtration rate (GFR*) >40 mL/min or Serum creatinine ≤ 1.5 x ULN 5. Total bilirubin ≤ 2.0 X ULN 6. AST, ALT, ALP ≤ 3.0 X ULN 6. Adequate pulmonary function without any clinical sign of severe pulmonary dysfunction. PFT > 50% FEV1 if clinically indicated by the investigator. 7. Negative serum pregnancy test if female and of childbearing potential (non-childbearing is defined as greater than one year postmenopausal or surgically sterilized). 8. Female participants of childbearing potential must adhere to using a medically accepted method of birth control prior to screening and agree to continue its use during the study or be surgically sterilized (e.g., hysterectomy or tubal ligation) and males must agree to use barrier methods of birth control while on study. 9. Provide signed informed consent and HIPPA authorization and agree to comply with all protocol-specified procedures and follow-up evaluations.
  • using the following Cockcroft-Gault equation to calculate the eGFR for this study: eGFR in mL/min = {(140-age in years) x (weight in kg) x F}/(serum creatinine in mg/dL x 72) Where F =1 if male; and 0.85 if female

Exclusion Criteria:

  1. Prior BCG treatment or known hypersensitivity to BCG. Patients who have received more than a single-dose post-operative treatment of mitomycin-C or gemcitabine are excluded.
  2. Concurrent use of other investigational agents.
  3. History of or evidence of muscle-invasive, locally advanced, metastatic and/or extravesical bladder cancer or any other cancer within the past 5 years, except: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage 1 or 2 cancer from which the patient is currently in complete remission, or stable prostate cancer (under active surveillance or hormone control).
  4. Symptomatic congestive heart failure (CHF), NYHA (New York Heart Association) Class III or IV or other clinical signs of severe cardiac dysfunction.
  5. Severe/unstable angina pectoris, or myocardial infarction within 6 months prior to study entry.
  6. History or evidence of uncontrollable CNS disease.
  7. Known HIV-positive.
  8. Active systemic infection requiring parenteral antibiotic therapy. All prior infections must have resolved following optimal therapy.
  9. Concurrent febrile illness, active urinary tract infection, active tuberculosis, a history of hypotension or anaphylactic reactions.
  10. Ongoing chronic systemic steroid therapy required (>10 mg oral prednisone daily or equivalent).
  11. Women who are pregnant or nursing. Female patients of childbearing potential must have a negative pregnancy test and must adhere to using a medically acceptable method of birth control prior to screening and agree to continue its use during the study and for 30 days after the last dose of study drug, or be surgically sterilized (e.g., hysterectomy or tubal ligation). Women of childbearing potential are defined as any female who has experienced menarche and who is NOT permanently sterile or postmenopausal. Postmenopausal is defined as 12 consecutive months with no menses without an alternative medical cause. Males must agree to use barrier methods of birth control while on study and for 90 days post last dose of study drug.
  12. Psychiatric illness/social situations that would limit compliance with study requirements.
  13. Other illness that in the opinion of the investigator would exclude the patient from participating in this study.

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The Role of the Vitamin D Receptor Gene Polymorphisms in Hepatocarcinogenesis in Cirrhotic Patients Infected With Chronic Hepatitis C Virus


Condition: Liver Cancer

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT02461979

Sponsor: Sherief Abd-Elsalam

Eligibility:

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

Inclusion Criteria:

  • Hcv cirrhotic patient with and without Hcc

Exclusion Criteria:

  • Malignancy other than HCC
  • Co-infection with Hepatitis B virus (HBV) and Human immunodeficiency virus (HIV)
  • Cirrhosis is due to causes other than chronic hepatitis C

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