NCT03317158
Modern Immunotherapy in BCG-Unresponsive, BCG-Relapsing and High Risk BCG-Naive Non-Muscle Invasive Urothelial Carcinoma of the Bladder
Active, Not Recruiting
PHASE1Ages 18+InterventionalTreatmentNoah Hahn, M.D.Investigator-initiated
~186 participants
Updated 2026-07-15 on ClinicalTrials.gov
What's tested:Durvalumab (Cohort 1-3)External Beam Radiotherapy (EBRT)Bacillus Calmette-Guérin (BCG)GemcitabineDocetaxelTremelimumab
At a glance
Recruiting sites
0 of 9 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Phase 1: Determine the recommended phase 2 dose (RP2D) from BCG-unresponsive non-muscle invasive bladder cancer (NMIBC)
Measured over 6 months
+1 more outcome measured
Conditions
Where it's being run
9 sites across 9 statesArizona1
Indiana1
Iowa1
Maryland1
Missouri1
Nebraska1
New York1
North Carolina1
Study leadership
- Noah M. Hahn, MD · PRINCIPAL_INVESTIGATOR · Hoosier Cancer Research Network
Who to contact
This trial hasn't published a contact. View it on ClinicalTrials.gov
Do you actually qualify for this trial?
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Eligibility criteria
Inclusion
ECOG (WHO) performance status 0 or 1
Age ≥ 18 years old at time of consent
Adequate hematologic, hepatic, and renal function as defined by the following laboratory parameters:
White blood cell count (WBC) \> 3.0 K/mm3
Absolute neutrophil count (ANC) ≥ 1.5 K/mm3
Platelets ≥ 100 K/mm3
Hemoglobin (Hgb) ≥ 9 g/dL
Serum total bilirubin: ≤ 1.5 x ULN
ALT and AST ≤ 2.5 x ULN
Serum creatinine clearance (CrCl) ≥ 30 mL/min using the modified Cockcroft- Gault equation
Subjects who give a written informed consent obtained according to local guidelines
Persistent or recurrent CIS with or without the presence of concurrent Ta or T1 tumors within 12 months of completion of adequate BCG therapy
Recurrent high-grade Ta or T1 tumors within 6 months of completion of adequate BCG therapy.
Persistent T1 high-grade tumors at the first disease evaluation (e.g. 3- month post-treatment evaluation) following an adequate BCG induction course
Prostatic urethra involvement of NMIBC
Adequate BCG therapy is defined as at least one of the following:
At least 5 of 6 doses of an initial induction BCG course plus at least 2 of 3 doses of maintenance therapy
At least 5 of 6 doses of an initial induction BCG course plus at least 2 of 6 doses of a second induction course.
Low-risk Tumors: Initial or recurrent tumor \> 12 months after resection with all of the following:
Solitary tumor
Low-grade
\< 3 cm
No CIS
Intermediate-Risk Tumors
High-risk Tumors. Any of the following:
High-grade
CIS
Multiple and recurrent and large (\> 3 cm) Ta low-grade tumors (all conditions must be met for this point on Ta low-grade tumors) • BCG-unresponsive, BCG-relapsing, BCG-persistent, or high-risk BCG-naïve NMIBC defined as follows: NOTE: Patients enrolling to phase 2 will enroll separately into a maximum of three expanded cohorts defined by the BCG exposure population eligibility criteria defined below (BCG-unresponsive, BCG-relapsing, BCG-persistent, and high-risk BCG-naïve). The three possible cohorts for each regimen expanded to phase 2 enrollment will be: BCG-unresponsive, BCG-relapsing and/or BCG-persistent (combined within a single cohort), and high-risk BCG-naïve. It is not anticipated that all three possible phase 2 expansion cohort populations will be pursued for every regimen entering phase 2 expansion. Questions regarding phase 2 expansion cohort populations and patient eligibility should be directed to the study chair. The individual eligibility for phase 2 expanded cohorts according to BCG exposure history are summarized below.
BCG-unresponsive NMIBC phase 2 expanded cohort. BCG-unresponsive NMIBC is defined by any of the following:
Persistent or recurrent CIS with or without the presence of concurrent Ta or T1 tumors within 12 months of completion of adequate BCG therapy
Recurrent high-grade Ta or T1 tumors within 6 months of completion of adequate BCG therapy.
Persistent T1 high-grade tumors at the first disease evaluation (e.g. 3-month post-treatment evaluation) following an adequate BCG induction course
Prostatic urethra involvement of NMIBC
At least 5 of 6 doses of an initial induction BCG course plus at least 2 of 3 doses of maintenance therapy
At least 5 of 6 doses of an initial induction BCG course plus at least 2 of 6 doses of a second induction course NOTE: Patients who satisfy the above definition of BCG-unresponsive NMIBC continue to be considered BCG-unresponsive regardless of the receipt of any intervening or additional non-BCG based intravesical therapies (e.g. chemotherapy, non-BCG investigational agents)
BCG-relapsing and/or BCG-persistent NMIBC phase 2 expanded Cohort. BCG-relapsing and/or BCG-persistent NMIBC is defined by either of the following:
BCG-persistent NMIBC is defined as persistent high-risk NMIBC at the first disease evaluation after initial BCG induction therapy (with no intervening achievement of complete response) for which a second course of BCG induction therapy is considered a standard of care (e.g. CIS or high grade Ta tumors) which does not meet any of the BCG-unresponsive criteria outlined in the protocol.
High-risk BCG-naive NMIBC cohort. High-risk BCG-naive NMIBC is defined as high-risk NMIBC in a patient that has never received intravesical BCG therapy. NOTE: Patients who satisfy the above definition of BCG-unresponsive NMIBC continue to be considered BCG-unresponsive regardless of the receipt of any intervening or additional non-BCG based intravesical therapies (e.g. chemotherapy, non-BCG investigational agents)
Patients with Grade ≥ 2 neuropathy will be evaluated on a case-by- case basis after consultation with the sponsor-investigator.
Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the sponsor-investigator.
Subjects who have received prior therapy with PD-1, PD-L1, or CTLA-4 directed agents.
Exclusion
Subjects with muscle-invasive (i.e. T2, T3, T4) locally advanced unresectable, or metastatic urothelial carcinoma as assessed on baseline radiographic imaging obtained within 60 days prior to study registration. The required radiographic imaging includes:
Abdomen/Pelvis - CT scan
Chest - chest x-ray or CT scan
Subjects with another active second malignancy other than non-melanoma skin cancers and biochemical relapsed prostate cancer. Subjects that have completed all necessary therapy and are considered to be at less than 30% risk of relapse are not considered to have an active second malignancy and are eligible for enrollment.
Subjects 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.
Subjects 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 subjects 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
Subjects with any of the following concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study:
Clinically significant cardiac diseases, including any of the following:
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)
Uncontrolled hypertension defined by a SBP ≥ 160 mm Hg and/or DBP ≥ 100 mm Hg, with or without anti-hypertensive medication(s)
Cirrhosis
Active Infection (includes chronic active and chronic persistent)
Hepatitis C. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
Known diagnosis of human immunodeficiency virus (HIV/positive HIV 1/2 antibodies) infection (HIV testing is not mandatory)
Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.\]). The following are exceptions to this criterion:
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
Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions to this criterion:
Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
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 sponsor-investigator.
Pregnant or breast-feeding women. Women of child-bearing potential must have a negative serum test ≤ 14 days prior to starting study drug.
Women of child-bearing potential, who are biologically able to conceive, and not employing contraception as described in the protocol.
Fertile males not willing to use contraception, as stated in the protocol.
Subjects unwilling or unable to comply with the protocol
Receipt of live attenuated vaccine within 30 days prior to the first dose of IP.
What this trial measures
- Phase 1: Determine the recommended phase 2 dose (RP2D) from BCG-unresponsive non-muscle invasive bladder cancer (NMIBC)6 months
Determine the recommended phase 2 dose (RP2D) from BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) patients treated with each of the following immunotherapy study regimens: Durvalumab (cohort 1) Durvalumab + intravesical BCG (cohort 2) Durvalumab + radiation (cohort 3) Durvalumab + intravesical Gemcitabine + intravesical Docetaxel (cohort 4) Durvalumab + Tremelimumab + intravesical Gemcitabine + intravesical Docetaxel (cohort 5) Intravesical NAI + intravesical Gemcitabine (cohort 6) Intravesical NAI + intravesical Gemcitabine + intravesical Docetaxel (cohort 7) Subcutaneous NAI + intravesical NAI + intravesical Gemcitabine + intravesical Docetaxel (cohort 8) The RP2D of each immunotherapy study arm is defined as the dose level at which \< 2 out of 6, \< 4 out of 9, or \< 5 out of 12 patients enrolled within an individual study arm experience dose-limiting toxicity.
- Phase 2: Determine the complete response rate within individual phase 2 expansion cohorts of BCG-unresponsive, BCG-relapsing/persistent, and high-risk BCG-naïve NMIBC subjects treated with each study regimen6 months
The complete response rate within each study arm is defined as the proportion of patients within each arm that demonstrate no evidence of recurrent or persistent high grade urothelial carcinoma of the bladder of any stage at any post-treatment disease assessment.