RECRUITING

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

Conditions

Urothelial Carcinoma Bladder Cancer non-muscle invasive bladder cancer BCG immunotherapy

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

Upon successful screening and registration, enrollment to durvalumab monotherapy (cohort 1) will begin. If DLT criteria outlined in the protocol are exceeded with durvalumab monotherapy (cohort 1), the study will close. Provided the safety of durvalumab monotherapy is established, enrollment to combination regimen cohorts will proceed. Cohorts will simultaneously enroll in parallel to each other with patients assigned to cohorts based on patient slot availability and study site choice of radiation arm participation. Patient assignment to future phase 1 arms would proceed similarly. Within BCG-containing cohorts, treatment will begin at full-dose BCG. If DLT criteria outlined in Section 5.1.4 are exceeded with full-dose BCG, a one level dose reduction of BCG will be implemented. If DLT criteria outlined in Section 5.1.4 are exceeded with reduced-dose BCG, the BCG-containing cohort will not proceed to Phase 2 of the study. Similarly, if DLT criteria outlined in Section 5.1.4 are exceeded within non-BCG containing cohorts, the non-BCG containing cohort will not proceed to phase 2 of the study. Due to the prolonged half-life of antibody therapies, no dose adjustments are planned for durvalumab in any of the cohorts.

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

Quick Facts

Study Start:2017-11-21

Study Completion:2025-12-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT03317158

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
Age 18 years or older Willing and able to provide informed consent Able to understand and follow study procedures Stable medical condition	* 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 4-6 Grade ≥ 2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria * 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. * 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 * 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: * Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection) * 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. 3.2.2 Exclusion Criteria (Cohorts 4 and 5 Only)

Inclusion Criteria

Exclusion Criteria

Age 18 years or older
Willing and able to provide informed consent
Able to understand and follow study procedures
Stable medical condition

* 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 4-6 Grade ≥ 2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria
* 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.
* 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
* 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:
* Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection)
* 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.
3.2.2 Exclusion Criteria (Cohorts 4 and 5 Only)

Contacts and Locations

Study Contact

Noah Hahn, MD

CONTACT

443-287-2886

nhahn4@jhmi.edu

Gabrielle Tiggs

CONTACT

317-634-5842

gtiggs@hoosiercancer.org

Principal Investigator

Noah M. Hahn, MD

PRINCIPAL_INVESTIGATOR

Hoosier Cancer Research Network

Study Locations (Sites)

BCG Oncology

Phoenix, Arizona, 85032

United States

Stanford University

Stanford, California, 94305

United States

Rush University Medical Cneter

Chicago, Illinois, 60612

United States

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202

United States

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242

United States

Johns Hopkins University: Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21231

United States

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215

United States

Washington University School of Medicine

Saint Louis, Missouri, 63110

United States

University of Nebraska Medical Center

Omaha, Nebraska, 68198

United States

Columbia University Irving Medical Center

New York, New York, 10032

United States

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599

United States

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111

United States

Collaborators and Investigators

Sponsor: Noah Hahn, M.D.

Noah M. Hahn, MD, PRINCIPAL_INVESTIGATOR, Hoosier Cancer Research Network

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2017-11-21

Study Completion Date2025-12-31

Study Record Updates

Study Start Date2017-11-21

Study Completion Date2025-12-31

Terms related to this study

Keywords Provided by Researchers

non-muscle invasive bladder cancer
BCG
immunotherapy

Additional Relevant MeSH Terms

Urothelial Carcinoma
Bladder Cancer