Genistein Therapy (GIBBS Study)
Randomized Placebo-Controlled Clinical Trial of Genistein in Reducing the Toxicity and Improving the Efficacy of Intravescial Therapy
Inclusion Criteria:
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Diagnosis of superficial bladder cancer
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Scheduled for BCG intravesical therapy tab
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Willing and able to give blood sample
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Willing and able to fill out a pill diary to ensure compliance
Exclusion Criteria:
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Pregnant patients
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Diagnosis of invasive bladder cancer
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HIV positive or immunocompromised
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Presence of concurrent second cancer (active, not history)
Principal Investigator:
Omer Kucuk, MD (Department of Hematology and Medical Oncology)
Co-Investigators & Collaborators:
BMS-CA2099UT
Phase 2, Randomized, Open-label Study of Nivolumab or Nivolumab/BMS-986205 Alone or Combined with Intravesical BCG in Participants with BCG-Unresponsive, High-Risk, Non-Muscle Invasive Bladder Cancer (CheckMate 9UT: CHECKpoint pathway and nivoluMAb clinical Trial Evaluation 9UT)
Inclusion Criteria:
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Pathologically demonstrated BCG-unresponsive*, high-risk NMIBC defined as carcinoma in situ (CIS) with or without papillary component, any T1, or Ta high-grade lesions; diagnosis required within 8 weeks (56 days) prior to starting treatment and must be confirmed by the Pathology Review Committee (PRC)
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Predominant histologic component (> 50%) must be urothelial (transitional cell) carcinoma
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ECOG performance status of 0-1
Exclusion Criteria:
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Participants with an active, known or suspected autoimmune disease
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Participants with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll
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Prior malignancy active within the previous three years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, prostate cancer with evidence of undetectable Prostate Specific Antigen (PSA), or carcinoma in situ of the cervix or breast
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Participants with a personal or family (ie, in a first-degree relative) history of cytochrome b5 reductase deficiency (previously called methemoglobin reductase deficiency) or other diseases that put them at risk of methemoglobinemia. All participants will be screened for methemoglobin levels prior to randomization
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Participants with a history of G6PD deficiency or other congenital or autoimmune hemolytic disorders. All participants will be screened for G6PD deficiency prior to randomization
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Evidence of locally advanced disease or metastatic bladder cancer as seen in crosssectional images of the chest, abdomen, and pelvis
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Urothelial cancer (UC) in the upper genitourinary tract (kidneys, renal collecting systems, ureters) within 24 months of enrollment
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UC and/or CIS in the prostatic urethra within 12 months of enrollment
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Locally advanced disease demonstrated by pelvic examination, preferably performed under anesthesia
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Previous or concurrent muscle invasive or disseminated/metastatic bladder cancer
Principal Investigator:
Co-Investigators & Collaborators:
Mehmet Bilen, MD (Department of Hematology and Medical Oncology); Kenneth Ogan, MD
Janssen THOR-2
Randomized Phase 2 Study of Erdafitinib Versus Investigator Choice of Intravesical Chemotherapy in Subjects Who Received Bacillus Calmette-Guérin (BCG) and Recurred With High Risk Non-Muscle-Invasive Bladder Cancer (NMIBC) and FGFR Mutations or Fusions
Inclusion Criteria:
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Histologically confirmed, recurrent, non-muscle-invasive urothelial carcinoma of the bladder
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Any UCC variant is allowed
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At least one of the following tumor FGFR mutations or fusions as determined by local or central testing at the time of recurrence after BCG therapy: FGFR3 mutations (R248C, S249C, G370C, Y373C) or FGFR2 and FGFR3 gene fusions (FGFR2-BICC1, FGFR2-CASP7, FGFR3-TACC3, FGFR3-BAIAP2L1)
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BCG-unresponsive subjects must meet at least one of the following:
– Persistent or recurrent CIS alone or with recurrent Ta/T1 disease within 12 months of adequate BCG therapy (Cohort 2 only).
– Recurrent high-grade Ta/T1 disease within six months of completion of adequate BCG therapy.
– T1 high-grade at the first disease assessment following an induction BCG course. -
BCG experienced subjects must meet the following:
– Recurrent high-grade Ta/T1 disease within 12 months of completion of BCG therapy (At least five of six full doses of an initial induction course OR at least five of six full doses of an initial induction course plus at least 1 maintenance (two of three weekly doses) in a six-month period) -
Cohort 1: may be BCG-unresponsive or BCG experienced
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Cohort 2: must be BCG-unresponsive
Exclusion Criteria:
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Histologically confirmed, muscle-invasive (T2 or higher stage) urothelial carcinoma of the bladder
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Histopathology demonstrating any small cell component, pure adenocarcinoma, pure squamous cell carcinoma, or pure squamous CIS of the bladder
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Prior treatment with an FGFR inhibitor
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Active malignancies (i.e., progressing or requiring treatment change in the last 24 months) other than the disease being treated under study (UTUC is included in this)
Principal Investigator:
Co-Investigators & Collaborators:
Kenneth Ogan, MD; Shreyas Joshi, MD, MPH; Aaron Lay, MD; Mehmet Bilen, MD (Department of Hematology and Medical Oncology); Bradley Carthon, MD (Department of Hematology and Medical Oncology)
MK-3475-676
Phase 3, Randomized, Comparator-controlled Clinical Trial to Study the Efficacy and Safety of Pembrolizumab (MK-3475) in Combination with Bacillus Calmette-Guerin (BCG) in Participants with High-risk Non-muscle Invasive Bladder Cancer (HR NMIBC) that is Persistent or Recurrent Following BCG Induction
Inclusion Criteria:
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At least 18 years of age
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Non-muscle invasive (T1, high-grade Ta and/or CIS) transitional cell carcinoma (TCC) of bladder
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Treated with only one course of BCG induction (defined as at least five of six intravesical instillations of BCG over a 10 week period)
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After BCG induction, (1) persistent Ta and/or CIS or (2) recurrent T1, Ta and/or CIS (recurrence must be within 24 months of last exposure to BCG)
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ECOG Score of 0, 1, or 2
Exclusion Criteria:
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Persistent T1 within three to six months after start of BCG induction
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Muscle-invasive urothelial carcinoma
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Concurrent extra-vesical non-muscle invasive TCC of urothelium, upper tract, or prostate
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Pregnant or breastfeeding
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History of HIV infection, Hepatitis B, active tuberculosis
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Has received prior systemic anti-cancer therapy including investigational agents within four weeks of start of study treatment
Principal Investigator:
Co-Investigators & Collaborators:
Bradley Carthon, MD (Department of Hematology and Medical Oncology); Viraj Master, MD, PhD; Mehmet Bilen, MD (Department of Hematology and Medical Oncology)
MK-3475-905
Phase 3 Randomized Study of Cystectomy plus Perioperative Pembrolizumab versus Cystectomy Alone in Cisplatin-ineligible Participants with Muscle-invasive Bladder Cancer
Inclusion Criteria:
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Histologically confirmed diagnosis of muscle invasive bladder cancer (T2-T4aN0M0) with predominant (≥50%) urothelial histology (histology and presence of muscle invasion to be confirmed by BICR)
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Clinically non-metastatic bladder cancer (N0M0) determined by imaging (CT chest and CT or MRI of the abdomen/pelvis), confirmed by BICR
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Deemed eligible for RC + PLND by his/her urologist and/or oncologist and agree to undergo curative intent standard RC + PLND (including prostatectomy if applicable)
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Be ineligible for treatment with cisplatin, as defined by meeting at least one of the following criteria:
– Impaired renal function with measured or calculated CrCl 30 to 59 mL/min (calculated by Cockcroft-Gault method or measured by 24-hour urine collection)
– ECOG Performance Status 2
– CTCAE v.4 Grade ≥2 audiometric hearing loss (25 dB in two consecutive wave ranges)
– CTCAE v.4 Grade ≥2 peripheral neuropathy
– NYHA Class III heart failure -
ECOG Score of 0, 1, or 2
Exclusion Criteria:
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Known additional non-urothelial malignancy that is progressing or has required active treatment ≤3 years of study randomization
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Any prior systemic anti-neoplastic treatment for MIBC
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An abdomino-pelvic lymph node ≥15 mm in the short axis
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Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor
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Prior systemic anti-cancer therapy including investigational agents within three years prior to randomization
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Has received prior systemic anti-cancer therapy including investigational agents within four weeks of start of study treatment
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Any prior radiotherapy to the bladder
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Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within seven days prior the first dose of study drug
Principal Investigator:
Co-Investigators & Collaborators:
Bradley Carthon, MD (Department of Hematology and Medical Oncology); Viraj Master, MD, PhD; Mehmet Bilen, MD (Department of Hematology and Medical Oncology)
QED Proof 302
Phase 3, Multicenter, Double-Blind, Randomized, Placebo-Controlled Trial of Infigratinib for the Adjuvant Treatment of Subjects with Invasive Urothelial Carcinoma with Susceptible FGFR3 Genetic Alterations (PROOF 302)
Inclusion Criteria:
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Histologically or cytologically confirmed, invasive urothelial carcinoma with susceptible FGFR3 alterations within 120 days following nephroureterectomy, distal ureterectomy, or cystectomy
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If status post neoadjuvant chemotherapy, pathologic stage at surgical resection must be AJCC Stage ≥ ypT2 and/or yN+
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If not status post neoadjuvant chemotherapy, is ineligible to receive cisplatin-based adjuvant chemotherapy based on Galsky, et al. (2011):
– Creatinine clearance ≤60 mL/min, or
– CTCAE Grade ≥2 hearing loss, or
– CTCAE Grade ≥2 neuropathy -
If cisplatin ineligible, must meet the following criteria:
– Upper tract disease should be AJCC Stage ≥pT2 pN0-2 M0
– UBC should be AJCC Stage ≥pT3 or pN+ -
Must have a centrally reviewed negative postoperative CT or negative biopsy within 28 days before randomization to confirm absence of disease at baseline
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ECOG performance status of ≤2
Exclusion Criteria:
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Presence of positive surgical margins following nephroureterectomy, distal ureterectomy, or cystectomy
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Have received BCG or other intravesical therapy for NMIBC within previous 30 days
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Are currently receiving or are planning to receive during participation in this study, treatment with agents that are known strong inducers or inhibitors of CYP3A4, and medications which increase serum phosphorus and/or calcium concentration
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Have a history of primary malignancy within the past 3 years
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Have current evidence of corneal or retinal disorder/keratopathy
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Have a history and/or current evidence of extensive tissue calcification
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Have impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral infigratinib
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Have amylase or lipase >2.0 × ULNHave insufficient hepatic and renal function
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Have any other concurrent disease or condition that, in the view of the investigator, would interfere with study participation
Principal Investigator:
Co-Investigators & Collaborators:
Mehmet Bilen, MD (Department of Hematology and Medical Oncology); Bradley Carthon, MD (Department of Hematology and Medical Oncology); Kenneth Ogan, MD; Shreyas Joshi, MD, MPH; Aaron Lay, MD