Bladder Cancer Research & Trials

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:

• Histologically confirmed by BICR diagnosis of non-muscle invasive (T1, high-grade Ta and/or CIS) TCC of the bladder

• Have been treated with one adequate course of BCG induction therapy for the treatment of HR NMIBC defined as at least 5 intravesical instillations of BCG within a 10-week period of time; if more than one induction course or any maintenance therapy of BCG has been received, the participant is not eligible for this study

• Following adequate BCG induction therapy, must have persistent or recurrent HR NMIBC defined as:
  – HR NMIBC: Recurrent T1, high-grade Ta and/or CIS
  – Persistent: Remains present within 3 months (-2 weeks) to 6 months (+4 weeks) after start of BCG induction (Note: persistent T1 not eligible for study), or
  – Recurrent: Reappearance of high-risk NMIBC after achieving a CR or tumor- free state within 6 months (+ 4 weeks) after start of BCG induction. The recurrence must be within 24 months of last exposure to BCG [with up to an additional 56 days allowed to account for delays in the 24-month assessment].

Exclusion Criteria:

• Has persistent (remains present within 3 months (-2 weeks) to 6 months (+4 weeks) after start of BCG induction) T1 disease following an induction course of BCG

• Has muscle invasive (i.e., T2, T3, T4), locally advanced non-resectable or metastatic urothelial carcinoma

• Note: BICR confirmation of the absence of locally advanced or metastatic disease is required prior to participant randomization

• Has concurrent extra-vesical (i.e., urethra, ureter, renal pelvis) non-muscle invasive transitional cell carcinoma of the urothelium, concurrent upper tract involvement, or invasive prostatic TCC including T1 or greater disease, or ductal invasion

• Has received 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 (e.g., CTLA-4, OX-40, CD137).

Note: Participants with biopsy proven low-grade disease or CIS of the prostate are eligible.

Principal Investigator:

Kenneth Ogan, MD

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)

A Phase 1/2 Study of EG-70 as an Intravesical Administration to Patients with BCG-Unresponsive NMIBC and High-Risk NMIBC Patients who are BCG Naïve or Received Incomplete BCG Treatment (Phase 2)

Inclusion Criteria:

• BCG-unresponsive NMIBC with (CIS) w/ or w/o resected papillary tumors indicated for, ineligible for, or have elected not to undergo cystectomy:

  • persistent HG Ta, T1, or Tis after receiving iBCG (at least 5/6) or recurrence after 12 mo. of receiving iBCG (at least 5/6) or

  • T1 high grade disease residual at the first evaluation following iBCG (at least 5/6)

• Patients previously treated with investigational or approved checkpoint inhibitor (e.g., pembro) who failed treatment are eligible for inclusion 30 days post-treatment

• Male or non-pregnant, non-lactating female

• ECOG 0, 1 or 2

• Hematologic inclusion w/i 2 wks of tx:

  • a. Absolute neutrophil count >1,500/mm3.

  • b. Hemoglobin >9.0 g/dl.

  • c. Platelet count >100,000/mm3.

• Hepatic inclusion w/i 2 wks of Day 1:

  • Total bilirubin ≤1.5 ULN

  • Creatinine clearance >30 mL/min (measured using Cockcroft-Gault or eGFR)

  • AST and ALT ≤2.5 x ULN for the institution, alkaline phosphatase ≤2.5 x ULN for the institution, unless bone metastasis is present in the absence of liver metastasis.

• PT and PTT w/i normal limits at Screening.

• Must be able to retain study drug for 60 min

Exclusion Criteria:

• Any other malignancy diagnosed w/i 1 yr of study entry (except basal or squamous cell skin cancers or noninvasive cancer of the cervix)

• Concurrent tx with any chemotherapeutic agent.

• Treatment with pembro w/i 30 days prior to Screening.

• Treatment with last therapeutic agent w/i 30 days of Screening

• Hx vesicoureteral reflux or indwelling urinary stent.

• Participation in any other research protocol involving administration of an investigational agent within 1 mo prior to Day 1.

• Hx external beam radiation to the pelvis at any time or prostate brachytherapy w/i last 12 mo

• Hx interstitial lung disease and/or pneumonitis in patients who have previously received a PD-1 or PD-L1 inhibitor therapy.

• Evidence of metastatic disease.

• Hx difficult catheterization that would prevent administration of EG-70.

• Hx interstitial cystitis.

• Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy.

• Known HIV, Hep B, or Hep C

• Significant cardiovascular risk (e.g., coronary stenting within 8 wks, myocardial infarction within 6 mo).

Principal Investigator: 

Dr. Shreyas Joshi

A Phase 3, Multi-center, Randomized Study Evaluating Efficacy of TAR-200 in Combination With Cetrelimab Versus Concurrent Chemoradiotherapy in Participants With Muscle-Invasive Urothelial Carcinoma (MIBC) of the Bladder who are not Receiving Radical Cystectomy

Inclusion Criteria:

• Histologically proven, cT2-T4a N0, M infiltrating urothelial carcinoma

  • Participants with variant histologic subtypes (e.g squamous cell carcinoma) are allowed if urothelial differentiation is predominant

• Ineligible for or have elected not to undergo radical cystectomy

• All AEs associated with any prior surgery and/or intravesical therapy must have resolved to Grade < 2

• ECOG 0, 1, or 2.

• Thyroid function tests within normal range or stable on hormone supplementation per investigator assessment

• Adequate bone marrow, liver and renal function

Exclusion Criteria:

• Active malignancies other than the study disease

• No UC or histological variant at any site outside bladder

• Must not have diffuse CIS

• Participants must not have evidence of cT4b, or N1-3, or M1 w/i 42 days prior to randomization

• Evidence of bladder perforation

• A history of clinically significant polyuria w

• Received intervening serial intravesical chemotherapy or immunotherapy

• Participants with an active, known or suspected autoimmune disease.

• Hx allogeneic tissue/solid organ transplant

• Indwelling urinary catheters

• Clinically significant liver disease

• Concurrent UTI infection

• Hx of any significant drug allergy

• Interstitial lung disease or active non-infectious pneumonitis.

• Hx of uncontrolled cardiovascular disease

• Major sx w/i 4 wks before first dose (except TURBT)

• Must not have tumors larger than 3cm

Principal Investigator: 

Dr. Vikram Narayan

A Phase 3, Open-Label, Multi-Center, Randomized Study Evaluating the Efficacy and Safety of TAR-200 in Combination with Cetrelimab or TAR-200 Alone Versus Intravesical Bacillus Calmette-Guérin (BCG) in Participants with BCG-naïve High-Risk Non-Muscle Invasive Bladder Cancer (HR-NMIBC)

Inclusion Criteria:

• Histologically confirmed initial diagnosis by local pathology (within 90 days of the initial signed informed consent) of HR-NMIBC (high-grade Ta, any T1 or CIS), in participants who are BCG-naïve.

• BCG-naïve (participants who have not received prior intravesical BCG or who previously received but stopped BCG more than 3 years before date of randomization are eligible)

Exclusion Criteria:

• T2 disease

• Must not have had urothelial carcinoma or histological variant at any site outside of the urinary bladder (ie, urethra, ureter, or renal pelvis). Ta/any T1/CIS of the upper urinary tract (including renal pelvis and ureter) is allowable if treated with complete nephroureterectomy more than 24 months prior to randomization.

• N+ and/or M+ per blinded independent central review (BICR) of CT/MR Urography and chest CT

Principal Investigator:

Dr. Vikram Narayan

A Phase 2, Open-Label, Multi-Center, Randomized Study of TAR-200 in Combination with Cetrelimab and Cetrelimab Alone in Participants with Muscle-Invasive Urothelial Carcinoma of the Bladder who are Scheduled for Radical Cystectomy and are Ineligible for or Refusing Platinum-Based Neoadjuvant Chemotherapy

Inclusion Criteria:

• Histologically proven, cT2-T4a N0, M0 infiltrating UCC of bladder

• All adverse events associated with any prior surgery must have resolved to CTCAE version 5.0 Grade <2 prior to randomization

• Deemed eligible for and willing to undergo RC

Exclusion Criteria:

• Active malignancies including non-invasive cervical cancer, skin, Localized prostate cancer (N0M0), breast cancer, or any other active malignancies

• Participants must not have evidence of cT4b, or N1-3, or M1 disease based on central radiology staging

Principal Investigator:

Dr. Vikram Narayan

Blue Light Cystoscopy with Cysview (BLC with Cysview) Registry

Inclusion Criteria:

• Suspected or known non-muscle invasive bladder cancer on the basis of a prior cystoscopy, or undergoing surveillance cystoscopy for carcinoma of the bladder

Exclusion Criteria:

• Porphyria

• Gross hematuria

• Known hypersensitivity to hexaminolevulinate or aminolevulinate derivatives

Principal Investigator:

Dr. Vikram Narayan

The comparison of Intravesical Therapy and Surgery as Treatment Options (CISTO) for Bladder Cancer Study

Inclusion Criteria:

• Adult 18 years of age or older; and

• Presenting with high grade NMIBC established by anatomic pathology as tumor stage classification Tis, Ta, or T1, and with:

  • Pathology documentation from any hospital/clinic/medical center, and

  • More than 50% urothelial carcinoma component in the specimen

• History of high grade NMIBC established by anatomic pathology as tumor stage classification Tis, Ta or T1 ; and

• Attempted of received induction BCG (at least 3 out of 6 instillations) at any point in time; and

• In the previous 12 months, received at least one instillation of any intravesical agent (induction or maintenance) or an administration of systemic therapy for NMIBC treatment

Exclusion Criteria:

• Any plasmacytoid or small cell (neuroendocrine) component in the pathology (past or current  presentation)

• Previous history of cystectomy or radiation therapy for bladder cancer

• Previous history of muscle invasive bladder cancer or metastatic bladder cancer

• Any history of upper tract urothelial carcinoma

• Incarcerated in detention facility or in police custody at baseline/screening

• Contraindication to radical cystectomy

• Contraindication to medical therapy

• Unable to provide written informed consent in English

• Unable to be contacted for research surveys

• Planning to participate in a Phase 1 or Phase 2 interventional clinical Trial for NMIBC or any blinded interventional trial for NMIBC

Principal Investigator:

Viraj Master MD, PhD, FACS