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AzTrials

Urothelial CarcinomaPhase 1/2ADAPT-BLADDERNCT03317158

Modern Immunotherapy in BCG-Unresponsive, BCG-Relapsing and High Risk BCG-Naive Non-Muscle Invasive Urothelial Carcinoma of the Bladder

A Phase 1/2 study testing Durvalumab (Cohort 1-3), External Beam Radiotherapy (EBRT) and Bacillus Calmette-Guérin (BCG) in people with Urothelial Carcinoma and Bladder Cancer, run by Noah Hahn, M.D. at 9 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

Upon successful screening and registration, enrollment to a cohort will begin. If DLT criteria are exceeded in a cohort, that cohort will close and will not proceed to Phase 2 of the study. Provided the safety of a cohort is established, enrollment will continue. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Urothelial Carcinoma, Bladder Cancer
What is being tested?
Durvalumab (Cohort 1-3), External Beam Radiotherapy (EBRT) and Bacillus Calmette-Guérin (BCG)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
186 participants
Where
9 sitesUnited States
Study dates
21 Nov 2017to 31 Dec 2029
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Subject must meet all of the following applicable criteria to participate in this study:
  • Histologically confirmed non-muscle invasive urothelial carcinoma of the bladder (Ta, T1, or Tis stage) on TURBT obtained within 60 days of registration.
  • NOTE: Mixed histologies are permitted, provided a component of urothelial carcinoma is present. Patients with histologically confirmed non- muscle invasive urothelial carcinoma of the bladder (Ta, T1, or Tis stage) on prior TURBT who undergo re-resection of the tumor base to confirm the diagnosis and/or exclude the presence of muscle-invasive disease (T2 or greater) who do not have appreciable tumor in the re-resection TURBT are eligible to enroll provided their re-resection was obtained within 60 days of registration and they meet all other eligibility criteria.
  • 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:
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  • 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
  • In addition to the inclusion criteria required of all patients above, the following inclusion criteria are also required of patients enrolling to Phase 1 of the study.
  • BCG-unresponsive disease 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.
  • NOTE: In recognition of the fact that procedure scheduling factors beyond the control of the patient or treating physician may cause unintended delays in disease evaluations, patients with pure papillary tumors (Ta or T1) with no components of CIS with recurrence documented within 9 months of completion of adequate BCG therapy who meet all other eligibility criteria may be considered for enrollment after consultation with the study chair.
  • 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.
  • NOTE: In cohorts that administer intravenous systemic therapy as part of the treatment regimen (cohorts 1-5), patients with concurrent non-muscle high-grade invasive tumors (CIS, Ta, T1) in the prostatic urethra and/or concurrent non-invasive high-grade tumors (CIS, Ta) in the upper urinary tracts (ureter, renal pelvis) are permitted to enroll in Phase 1 of the study. Patients with concurrent high-grade T1 tumors in the upper urinary tracts (ureter, renal pelvis) are not eligible to enroll in Phase 1 of the study.
  • In cohorts that do not administer intravenous systemic therapy as part of the treatment regimen (cohorts 6-8), patients with concurrent non-muscle invasive high-grade tumors (CIS, Ta, T1) in the prostatic urethra and/or concurrent non-muscle invasive high-grade tumors (CIS, Ta, T1) in the upper urinary tracts (ureter, renal pelvis) are not eligible to enroll in Phase 1 of the study.
  • Patients who have met the BCG-unresponsive criteria at any time point in their treatment history are permitted to enroll in Phase 1 of the study regardless of the time frame between their most recent BCG treatment administration and study registration dates.
  • In addition to the inclusion criteria required of all patients above, the following inclusion criteria are also required of patients enrolling to Phase 2 of the study.
  • High-risk NMIBC defined according to modified EORTC risk criteria summarized as follows: NOTE: Intermediate- and Low-risk tumors as defined below are not eligible. NOTE: At least half of the subjects enrolled to each cohort must have a component of CIS present.
  • 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
  • --- All tumors not defined in the two adjacent categories (between the category of low and high risk)
  • High-risk Tumors. Any of the following:
  • --- T1 tumor
  • 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.
  • NOTE: In recognition of the fact that procedure scheduling factors beyond the control of the patient or treating physician may cause unintended delays in disease evaluations, patients with pure high-grade papillary tumors (Ta or T1) with no components of CIS with recurrence documented within 9 months of completion of adequate BCG therapy who meet all other eligibility criteria may be considered for enrollment after consultation with the study chair.
  • 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
  • o 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 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-relapsing NMIBC is defined as recurrent high-risk NMIBC after achievement of a complete response to BCG induction therapy which does not meet any of the BCG-unresponsive criteria outlined in the protocol.
  • 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)
  • Primary Exclusion Criteria:

Who cannot join

  • 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.
  • Any unresolved toxicity NCI CTCAE v4.03 for Cohorts 1-3 and v5.0 for cohorts 4-8 Grade ≥ 2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria
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  • 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.
  • Subjects who have had any prior radiation to the prostate or pelvis. NOTE: The exclusion of patients who have had any prior radiation to the prostate or pelvis applies to both phase 1 and 2 of the trial only within radiation containing study regimens. Patients with a prior history of prostate or pelvic radiation who meet all other eligibility criteria may be considered for phase 1 and phase 2 enrollment to non-radiation containing study regimens after consultation with the study chair.
  • 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:
  • --- History or presence of serious uncontrolled ventricular arrhythmias
  • --- Clinically significant resting bradycardia
  • 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)
  • --- Tuberculosis
  • --- Hepatitis B (known positive HBV surface antigen (HbsAg). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HbsAg) are eligible
  • 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:
  • --- Patients with vitiligo or alopecia
  • --- Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
  • --- Any chronic skin condition that does not require systemic therapy
  • --- Patients without active disease in the last 5 years may be included but only after consultation with the study physician
  • --- Patients with celiac disease controlled by diet alone
  • 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:
  • o Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection)
  • o Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
  • 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.
  • NOTE: Patients, if enrolled, should not receive live vaccine whilst receiving study drugs and up to 30 days after the last dose of study drug.
  • Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
  • 3.2.2 Exclusion Criteria (Cohorts 4, 5, 7, and 8 Only)
  • Subjects who have received prior intravesical therapy with BOTH gemcitabine and docetaxel NOTE: Patients who have received either intravesical gemcitabine or intravesical docetaxel (or other taxanes) but not both remain eligible. For example, patients receiving post-TURBT single dose intravesical gemcitabine administration are eligible. Similarly, patients treated with intravesical gemcitabine induction and/or maintenance are eligible. While we typically do not see patients treated with intravesical docetaxel (or other taxanes) monotherapy, if such a patient were identified and screened, they would be eligible. Patients who have received treatment with separate courses of intravesical gemcitabine monotherapy and intravesical docetaxel (or other taxanes) monotherapy are not eligible, unless such therapies occurred more than 24 months ago.
  • 3.2.3 Exclusion Criteria (Cohort 6 Only)
  • Subjects who have received prior intravesical induction therapy with gemcitabine NOTE: Patients treated with single-dose post-TURBT intravesical gemcitabine are eligible. Patients who have received intravesical induction therapy with gemcitabine are not eligible. While we typically do not see patients treated with intravesical docetaxel (or other taxanes) monotherapy, if such a patient were identified and screened, they would be eligible.
  • Exclusion Criteria (Phase 1 Only) In Phase 1 of the study, there are no additional exclusion criteria beyond those described of all patients above.
  • Exclusion Criteria (Phase 2 Only) In addition to the exclusion criteria described of all patients above, the following exclusion criteria apply to patients enrolling to Phase 2 of the study.
  • Subjects with prostatic urethra or concurrent upper urinary tract (i.e. ureter, renal pelvis) high-grade urothelial carcinoma. NOTE: Subjects with concurrent low-grade non-invasive (Ta) prostatic urethra or upper urinary tract urothelial carcinoma are eligible. Similarly, patients with a history of high-grade prostatic urethra or upper tract urothelial carcinoma that has been definitively treated with at least one post-treatment disease assessment (i.e. cytology, biopsy, imaging) that demonstrates no evidence of residual disease are eligible.

Trial locations and contacts

9 sites in 1 country.

9 sites in 1 country

United States9 sites

  • Johns Hopkins University: Sidney Kimmel Comprehensive Cancer Center

    Baltimore, Maryland, 21231

  • University of North Carolina at Chapel Hill

    Chapel Hill, North Carolina, 27599

  • Indiana University Melvin and Bren Simon Cancer Center

    Indianapolis, Indiana, 46202

  • University of Iowa Hospitals and Clinics

    Iowa City, Iowa, 52242

  • Columbia University Irving Medical Center

    New York, New York, 10032

  • University of Nebraska Medical Center

    Omaha, Nebraska, 68198

  • Fox Chase Cancer Center

    Philadelphia, Pennsylvania, 19111

  • BCG Oncology

    Phoenix, Arizona, 85032

  • Washington University School of Medicine

    St Louis, Missouri, 63110

Other trials in United States

About this study

Official title: PhAse 1/2 StuDy of Modern ImmunotherApy in BCG-Unresponsive, BCG-RelaPsing, and High-Risk BCG-Naive Non-muscle Invasive UroThelial Carcinoma of the BLADDER

Upon successful screening and registration, enrollment to a cohort will begin. If DLT criteria are exceeded in a cohort, that cohort will close and will not proceed to Phase 2 of the study. Provided the safety of a cohort is established, enrollment will continue. Within BCG-containing cohorts, treatment will begin at full-dose BCG. If DLT criteria are exceeded with full-dose BCG, a one level dose reduction of BCG will be implemented. If DLT criteria are exceeded with reduced-dose BCG, the BCG-containing cohort will not proceed to Phase 2 of the study

Phase 1 Cohorts:

Read more
  • Durvalumab Monotherapy (cohort 1); ENROLLMENT COMPLETE
  • Durvalumab plus BCG (cohort 2); ENROLLMENT COMPLETE
  • Durvalumab plus External Beam Radiotherapy (EBRT) (cohort 3); ENROLLMENT COMPLETE
  • Durvalumab plus Intravesical Gemcitabine plus Intravesical Docetaxel (cohort 4); ENROLLMENT COMPLETE
  • Durvalumab plus Tremelimumab plus Intravesical Gemcitabine plus Intravesical Docetaxel (cohort 5); ENROLLMENT DID NOT OCCUR
  • Intravesical N-803NAI plus Intravesical Gemcitabine (cohort 6)
  • Intravesical N-803NAI plus Intravesical Gemcitabine plus Intravesical Docetaxel (cohort 7)
  • Subcutaneous N-803NAI plus Intravesical N-803NAI plus Intravesical Gemcitabine plus Intravesical Docetaxel (cohort 8)

If any of the combination regimen cohorts establishes a RP2D in Phase 1 of the study, enrollment to Phase 2 of the study may proceed within the individual phase 2 expansion cohorts defined by patient BCG exposure history. Upon successful screening and registration, Phase 2 subjects will be assigned to one of the treatment arms. Assignment will occur amongst the arms that are open to accrual at the time of subject registration. Phase 2 subjects will be administered treatment at the RP2D's established for each regimen within Phase 1 of the study.

However, within BCG-containing cohorts, the BCG dose will be reduced to Dose level -1 (1/3rd-dose BCG) even if the RP2D established in the Phase 1 of the study was full-dose BCG. The rationale for this stems from ongoing global BCG supply shortages that have arisen since the launch of the trial and multiple prior clinical trials demonstrating similar efficacy with decreased toxicity when reduced-dose BCG regimens are utilized compared to full-dose BCG therapy. This modification was deemed necessary to facilitate continued enrollment to the study while not sacrificing clinical efficacy or safety. This modification also aligns with recent AUA consensus guidelines on BCG dosing during BCG shortages.

It is anticipated that individual treatment cohorts will be closed and added during the conduct of the study as cohorts complete accrual, individual cohort safety data is analyzed, and new cohorts are added. Enrollment to Phase 2 cohorts will not begin until at least one cohort has successfully established a RP2D in the Phase 1 portion of the study and deemed safe to proceed to the Phase 2 portion of the trial.

Being tested
Durvalumab (Cohort 1-3), External Beam Radiotherapy (EBRT), Bacillus Calmette-Guérin (BCG), Gemcitabine, Docetaxel
Keywords
non-muscle invasive bladder cancer, BCG, immunotherapy
Medical subject headings
Carcinoma, Transitional Cell, Urinary Bladder Neoplasms, Non-Muscle Invasive Bladder Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Durvalumab (Cohort 1-3)Drug

    Also called Imfinzi

    Durvalumab 1120 mg intravenously Day 1 every 21 days x 8 cycles.

  • External Beam Radiotherapy (EBRT)Radiation

    EBRT 6 Gy x 3; Cycle 1 Day 1, 3, and 5

  • Bacillus Calmette-Guérin (BCG)Biological

    Dose level 0 (starting dose) = Full-dose

    Dose level-1 = 1/3rd-dose BCG. Dose level -1 is expected to be utilized during the phase II portion of the study due to the ongoing and persistent shortage of BCG in the US.

  • GemcitabineDrug

    Also called Gemzar

    Gemcitabine 1000 mg intravesical weekly (+/- 2 days) x 6 doses

  • DocetaxelDrug

    Also called Taxotere

    Docetaxel 37.5 mg intravesical weekly (+/- 2 days) x 6 doses.

  • TremelimumabBiological

    Tremelimumab 75 mg intravenously Day 1 (+/- 2 days) every 28 days x 4 cycles.

  • Durvalumab (Cohort 4/5)Drug

    Also called Imfinzi

    Durvalumab 1500 mg intravenously Day 1 (+/- 2 days) every 28 days x 6 cycles.

  • To be determinedOther

    Other regimens to be determined

  • Intravesical NAI (Cohorts 6-7)Drug

    For all cohorts containing intravesical NAI treatment, starting in Week 1, induction intravesical NAI 400 ug will be administered weekly x 6 doses via a foley catheter into an empty bladder and maintained in the bladder for 60 minutes.

  • Subcutaneous NAI (Cohort 8)Drug

    For all cohorts containing subcutaneous NAI treatment, starting in Week 1, NAI 10 ug/kg will be administered biweekly for 3 doses via subcutaneous injection.

Study groups in NCT03317158
Study groupRoleWhat they receive
Phase 1: Cohort 1ExperimentalDurvalumab monotherapy
Receives: Drug: Durvalumab (Cohort 1-3)
Phase 1: Cohort 2ExperimentalDurvalumab plus BCG
Receives: Drug: Durvalumab (Cohort 1-3); Biological: Bacillus Calmette-Guérin (BCG)
Phase 1: Cohort 3ExperimentalDurvalumab plus External Beam Radiotherapy (EBRT) (BCG re-treatment) - Cross-over to Durvalumab Monotherapy
Receives: Drug: Durvalumab (Cohort 1-3); Radiation: External Beam Radiotherapy (EBRT)
Phase 1: Cohort 4ExperimentalDurvalumab + Gemcitabine/Intravesical Docetaxel (Gem/Doc) The sequence of administration is flexible to allow for scheduling of both the infusion and intravesical treatments.
Receives: Drug: Gemcitabine; Drug: Docetaxel; Drug: Durvalumab (Cohort 4/5)
Phase 1: Cohort 5ExperimentalNOTE: Cohort 5 was abandoned prior to any patients enrolled. Durvalumab + Tremelimumab + Gem/Doc The sequence of administration is flexible to allow for scheduling of both the infusion and intravesical treatments. For the intravenous medications, durvalumab should be administered first followed by tremelimumab.
Receives: Drug: Gemcitabine; Drug: Docetaxel; Biological: Tremelimumab; Drug: Durvalumab (Cohort 4/5)
Phase 1: Cohort 6ExperimentalIntravesical NAI plus Gemcitabine
Receives: Drug: Gemcitabine; Drug: Intravesical NAI (Cohorts 6-7)
Phase 2: Cohort 4 ExpansionExperimentalDurvalumab + Gemcitabine/Intravesical Docetaxel (Gem/Doc) The sequence of administration is flexible to allow for scheduling of both the infusion and intravesical treatments.
Receives: Drug: Gemcitabine; Drug: Docetaxel; Drug: Durvalumab (Cohort 4/5)
Phase 1: Cohort 7ExperimentalIntravesical NAI plus Gemcitabine and Docetaxel
Receives: Drug: Gemcitabine; Drug: Docetaxel; Drug: Intravesical NAI (Cohorts 6-7)
Phase 1: Cohort 8ExperimentalSubcutaneous NAI plus Intravesical NAI plus Gemcitabine and Docetaxel
Receives: Drug: Gemcitabine; Drug: Docetaxel; Drug: Intravesical NAI (Cohorts 6-7); Drug: Subcutaneous NAI (Cohort 8)
Phase 1: Cohort 9ExperimentalAdditional Regimens TBD
Receives: Other: To be determined

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Phase 1: Determine the recommended phase 2 dose (RP2D) from BCG-unresponsive non-muscle invasive bladder cancer (NMIBC)

    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.

    Measured: 6 months

  2. 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 regimen

    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.

    Measured: 6 months

Secondary outcomes (6)

  1. Phase 1: Assess Adverse Events

    The safety profile of BCG-unresponsive NMIBC subjects treated within each study regimen will be assessed by NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.03 for Cohorts 1-3 and v5.0 for Cohorts 4-8.

    Measured: 6 months

  2. Phase 1: Characterize the complete response rate of BCG-unresponsive NMIBC subjects treated with each study regimen

    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.

    Measured: 2 years (24 months)

  3. Phase 1: Characterize the 12-month recurrence free survival (RFS) rate of BCG-unresponsive NMIBC subjects treated with each study regimen

    The 12-month RFS rate of BCG-unresponsive NMIBC subjects treated within each study regimen is defined as the proportion of patients within each arm with no evidence of recurrent high grade urothelial carcinoma of the bladder of any stage at the 12-month post-treatment disease assessment.

    Measured: 12 month

  4. Phase 2: Determine the 12-month RFS rate within individual phase 2 expansion cohorts of BCG-unresponsive, BCG-relapsing/persistent, and high-risk BCG-naive NMIBC subjects treated with each study regimen

    The 12-month RFS rate of BCG-unresponsive, BCG-relapsing/persistent, and high-risk BCG-naive NMIBC subjects treated within each arm is defined as the proportion of patients within each arm with no evidence of recurrent high grade urothelial carcinoma of the bladder of any stage at the 12-month post-treatment assessment.

    Measured: 12 months

  5. Phase 2: Identify significant associations between complete response rates and 12-month RFS rates and baseline tumor immunohistochemistry staining patterns of PD-L1 and other relevant mechanism of action targets for each study regimen

    Associations between complete response rate and 12-month RFS rates will be assessed by baseline tumor immunohistochemistry staining patterns of PD-L1 (assessed by the SP263 PD-L1 antibody) and other relevant mechanism of action targets for each drug.

    Measured: 12 months

  6. Phase 2: Assess Adverse Events

    The safety profile within individual phase 2 expansion cohorts of BCG-unresponsive, BCG-relapsing/persistent, and high-risk BCG-naive NMIBC subjects treated within each study arm will be assessed by NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.03 for Cohorts 1-3 and v5.0 for Cohorts 4-8.

    Measured: 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Oct 2017
  2. Study start21 Nov 2017
  3. Primary completion31 Dec 2028 (estimated)
  4. Study completion31 Dec 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Masking
None (open label)
Enrolment
186 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03317158
Sponsor's protocol ID
HCRN GU16-243
Acronym
ADAPT-BLADDER
Status last verified
Jul 2026
First submitted
12 Oct 2017
Last updated
15 Jul 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Durvalumab (Cohort 1-3), External Beam Radiotherapy (EBRT) and Bacillus Calmette-Guérin (BCG) in people with Urothelial Carcinoma and Bladder Cancer, run by Noah Hahn, M.D. at 9 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 55 inclusion and 49 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 15 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase 1: Determine the recommended phase 2 dose (RP2D) from BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) (time frame: 6 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03317158.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jul 2026.

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