S1602: Different Strains of BCG With or Without Vaccine in High Grade Non- Muscle Invasive Bladder Cancer

Stage 0is Bladder Urothelial Carcinoma Clinical Trial

Official title:

S1602, A Phase III Randomized Trial to Evaluate the Influence of BCG Strain Differences and T Cell Priming With Intradermal BCG Before Intravesical Therapy for BCG-Naive High-Grade Non-muscle Invasive Bladder Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03091660
• Other study ID #: S1602
• Secondary ID: NCI-2016-00451S1
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: February 24, 2017
• Est. completion date: February 2025

Study information

• Verified date: May 2024
• Source: SWOG Cancer Research Network
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This randomized phase III trial studies Tokyo-172 strain bacillus Calmette-Guerin (BCG) solution with or without a vaccination using Tokyo-172 strain BCG to see how well it works compared with TICE BCG solution in treating patients with bladder cancer that has not spread to muscle. BCG is a non-infectious bacteria that when instilled into the bladder may stimulate the immune system to fight bladder cancer. Giving different versions of BCG with vaccine therapy may prevent bladder cancer from returning.

Description:

PRIMARY OBJECTIVES:

I. To compare whether time to high grade recurrence (TTHGR) for patients with BCG-naïve, non-muscle invasive bladder cancer (NMIBC) receiving Tokyo-172 BCG strain (Arm II) is non-inferior to patients receiving TICE BCG strain (Arm I).

II. To test whether TTHGR for patients with BCG-naïve, NMIBC receiving intradermal Tokyo-172 BCG vaccination followed by intravesical Tokyo-172 BCG instillation (Arm III) is superior to patients receiving intravesical Tokyo-172BCG instillation without prior intradermal BCG vaccination (Arm II).

SECONDARY OBJECTIVES:

I. To compare time to recurrence (TTR) with any-grade (AG) bladder cancer between patients receiving Tokyo-172 versus TICE BCG strain.

II. To compare TTR with AG bladder cancer between patients receiving intradermal + intravesical versus intravesical only Tokyo-172 BCG.

III. To compare progression-free survival (PFS) between patients receiving Tokyo-172 versus TICE BCG strain.

IV. To compare PFS between patients receiving intradermal + intravesical versus intravesical only Tokyo-172 BCG.

V. To compare 6-month complete response in patients with carcinoma in situ (CIS) with or without Ta or T1 cancer present at baseline receiving Tokyo-172 versus TICE BCG strain.

VI. To compare 6-month complete response in patients with CIS with or without Ta or T1 cancer present at baseline receiving intradermal + intravesical versus intravesical only Tokyo-172 BCG.

TERTIARY OBJECTIVES:

I. To test the hypothesis that purified protein derivative (PPD) test conversion (positive PPD at 3 or 6 months) following BCG immunotherapy will predict time to high grade recurrence (TTHGR).

II. To test the hypothesis that urinary cytokine levels following BCG immunotherapy will predict time to high grade recurrence (TTHGR).

III. To test the hypothesis that tumor neoantigen burden and T lymphocyte infiltration are associated with BCG response.

OUTLINE: Patients are randomized to 1 of 3 treatment arms.

ARM I:

INDUCTION: Patients receive TICE BCG solution intravesically once a week for 6 weeks.

MAINTENANCE: Patients receive TICE BCG solution once a week for 3 consecutive weeks at months 3, 6, 12, 18, 24, 30, and 36 for up to 7 doses.

ARM II:

INDUCTION: Patients receive Tokyo-172 strain BCG solution intravesically once a week for 6 weeks.

MAINTENANCE: Patients receive Tokyo-172 strain BCG solution once a week for 3 consecutive weeks at months 3, 6, 12, 18, 24, 30, and 36 for up to 7 doses.

ARM III:

PRIME: Patients receive Tokyo-172 strain BCG vaccine once intradermally (ID).

INDUCTION: Within 21 days, patients receive Tokyo-172 strain BCG solution as in Arm II.

MAINTENANCE: Patients receive Tokyo-172 strain BCG solution as in Arm II.

After completion of study treatment, patients are followed up for 5 years.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1000
• Est. completion date: February 2025
• Est. primary completion date: December 15, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Patients must have histologically proven Ta, carcinoma in situ (CIS) or T1 stage urothelial cell carcinoma of the bladder within 90 days of registration

• Patients must have had all grossly visible papillary tumors removed within 30 days prior to registration or cystoscopy confirming no grossly visible papillary tumors within 30 days prior to registration

• Patients with T1 disease must have cross-sectional imaging of abdomen/pelvis demonstrating no evidence of metastatic disease (magnetic resonance imaging [MRI] or computed tomography [CT] scan) within 90 days prior to registration; patients with T1 disease must have re-resection confirming =< T1 disease within 90 days prior to registration

• Patients must have high-grade bladder cancer as defined by 2004 World Health Organization (WHO)/International Society of Urological Pathology (ISUP) classification

• Patients must not have pure squamous cell carcinoma or adenocarcinoma

• Patients' disease must not have micropapillary components

• Patients must have no evidence of upper tract (renal pelvis or ureters) cancer confirmed by one of the following tests performed within 90 days prior to registration: CT urogram, intravenous pyelogram, magnetic resonance (MR) urogram, or retrograde pyelograms

• Patients must not have nodal involvement or metastatic disease

• No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for five years; patients with localized prostate cancer who are being followed by an active surveillance program are also eligible

• Patients must have a Zubrod performance status of 0-2

• Patients must not have received prior intravesical BCG

• Patients must not have known history of tuberculosis

• Patients must be PPD negative within 90 days prior to registration; PPD negativity is defined as < 10 mm diameter induration (palpable, raised hardened area) in the volar forearm at 48-72 hours following injection with standard tuberculin dose (5 units, 0.1 ml)

• Patients must be >= 18 years of age

• Patients must not be taking oral glucocorticoids at the time of registration

• Patients must not be planning to receive concomitant biologic therapy, hormonal therapy, chemotherapy, surgery, or other cancer therapy while on study

• Prestudy history and physical must be obtained within 90days prior to registration

• Patients must not be pregnant or nursing; women/men of reproductive potential must have agreed to use an effective contraceptive method; a woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months; in addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation; however, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures

• Patients must be offered the opportunity to participate in specimen banking for future studies to include translational medicine studies

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Transitional Cell
• Stage 0 Bladder Urothelial Carcinoma
• Stage 0is Bladder Urothelial Carcinoma
• Stage I Bladder Urothelial Carcinoma

Intervention

Biological:
• BCG Solution
Given intravesically
• BCG Tokyo-172 Strain Solution
Given intravesically
• BCG Tokyo-172 Strain Vaccine
Given ID

Other:
• Laboratory Biomarker Analysis
Correlative studies

Locations

Country	Name	City	State
United States	Hawaii Cancer Care - Savio	'Aiea	Hawaii
United States	Pali Momi Medical Center	'Aiea	Hawaii
United States	Queen's Cancer Center - Pearlridge	'Aiea	Hawaii
United States	Saint Joseph Mercy Hospital	Ann Arbor	Michigan
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	University of Colorado Hospital	Aurora	Colorado
United States	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland
United States	Memorial Sloan Kettering Basking Ridge	Basking Ridge	New Jersey
United States	Indu and Raj Soin Medical Center	Beavercreek	Ohio
United States	Prisma Health Cancer Institute - Spartanburg	Boiling Springs	South Carolina
United States	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho
United States	Saint Luke's Cancer Institute - Boise	Boise	Idaho
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Henry Ford Cancer Institute-Downriver	Brownstown	Michigan
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Saint Alphonsus Cancer Care Center-Caldwell	Caldwell	Idaho
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
United States	Centralia Oncology Clinic	Centralia	Illinois
United States	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina
United States	Ralph H Johnson VA Medical Center	Charleston	South Carolina
United States	Northwestern University	Chicago	Illinois
United States	University of Illinois	Chicago	Illinois
United States	Marshfield Clinic-Chippewa Center	Chippewa Falls	Wisconsin
United States	Prisma Health Cancer Institute - Laurens	Clinton	South Carolina
United States	Henry Ford Macomb Hospital-Clinton Township	Clinton Township	Michigan
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Memorial Sloan Kettering Commack	Commack	New York
United States	Bay Area Hospital	Coos Bay	Oregon
United States	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas
United States	Carle on Vermilion	Danville	Illinois
United States	Henry Ford Medical Center-Fairlane	Dearborn	Michigan
United States	Atlanta VA Medical Center	Decatur	Georgia
United States	Cancer Care Specialists of Illinois - Decatur	Decatur	Illinois
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	Henry Ford Hospital	Detroit	Michigan
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Prisma Health Cancer Institute - Easley	Easley	South Carolina
United States	Marshfield Medical Center-EC Cancer Center	Eau Claire	Wisconsin
United States	Carle Physician Group-Effingham	Effingham	Illinois
United States	Crossroads Cancer Center	Effingham	Illinois
United States	Arnot Ogden Medical Center/Falck Cancer Center	Elmira	New York
United States	Englewood Hospital and Medical Center	Englewood	New Jersey
United States	Farmington Health Center	Farmington	Utah
United States	Saint Luke's Cancer Institute - Fruitland	Fruitland	Idaho
United States	University of Florida Health Science Center - Gainesville	Gainesville	Florida
United States	University of Texas Medical Branch	Galveston	Texas
United States	Banner MD Anderson Cancer Center	Gilbert	Arizona
United States	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana
United States	Prisma Health Cancer Institute - Butternut	Greenville	South Carolina
United States	Prisma Health Cancer Institute - Eastside	Greenville	South Carolina
United States	Prisma Health Cancer Institute - Faris	Greenville	South Carolina
United States	Prisma Health Greenville Memorial Hospital	Greenville	South Carolina
United States	Prisma Health Cancer Institute - Greer	Greer	South Carolina
United States	Memorial Sloan Kettering Westchester	Harrison	New York
United States	Comprehensive Cancer Centers of Nevada - Henderson	Henderson	Nevada
United States	Comprehensive Cancer Centers of Nevada-Horizon Ridge	Henderson	Nevada
United States	Comprehensive Cancer Centers of Nevada-Southeast Henderson	Henderson	Nevada
United States	Las Vegas Urology - Green Valley	Henderson	Nevada
United States	Las Vegas Urology - Pebble	Henderson	Nevada
United States	OptumCare Cancer Care at Seven Hills	Henderson	Nevada
United States	Urology Specialists of Nevada - Green Valley	Henderson	Nevada
United States	Island Urology-Hilo	Hilo	Hawaii
United States	Hawaii Cancer Care Inc - Waterfront Plaza	Honolulu	Hawaii
United States	Island Urology	Honolulu	Hawaii
United States	Queen's Cancer Cenrer - POB I	Honolulu	Hawaii
United States	Queen's Cancer Center - Kuakini	Honolulu	Hawaii
United States	Queen's Medical Center	Honolulu	Hawaii
United States	Straub Clinic and Hospital	Honolulu	Hawaii
United States	University of Hawaii Cancer Center	Honolulu	Hawaii
United States	Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center	Houston	Texas
United States	Houston Methodist Hospital	Houston	Texas
United States	M D Anderson Cancer Center	Houston	Texas
United States	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa
United States	Baptist MD Anderson Cancer Center	Jacksonville	Florida
United States	Kettering Medical Center	Kettering	Ohio
United States	Gundersen Lutheran Medical Center	La Crosse	Wisconsin
United States	Marshfield Clinic - Ladysmith Center	Ladysmith	Wisconsin
United States	Sparrow Hospital	Lansing	Michigan
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada - Central Valley	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada - Northwest	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada - Town Center	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada-Summerlin	Las Vegas	Nevada
United States	Hope Cancer Care of Nevada	Las Vegas	Nevada
United States	Las Vegas Prostate Cancer Center	Las Vegas	Nevada
United States	Las Vegas Urology - Cathedral Rock	Las Vegas	Nevada
United States	Las Vegas Urology - Pecos	Las Vegas	Nevada
United States	Las Vegas Urology - Smoke Ranch	Las Vegas	Nevada
United States	Las Vegas Urology - Sunset	Las Vegas	Nevada
United States	OptumCare Cancer Care at Fort Apache	Las Vegas	Nevada
United States	OptumCare Cancer Care at MountainView	Las Vegas	Nevada
United States	OptumCare Cancer Care at Oakey	Las Vegas	Nevada
United States	Radiation Oncology Centers of Nevada Central	Las Vegas	Nevada
United States	Urology Specialists of Nevada - Central	Las Vegas	Nevada
United States	Urology Specialists of Nevada - Northwest	Las Vegas	Nevada
United States	Urology Specialists of Nevada - Southwest	Las Vegas	Nevada
United States	UTMB Cancer Center at Victory Lakes	League City	Texas
United States	Cedars Sinai Medical Center	Los Angeles	California
United States	Los Angeles County-USC Medical Center	Los Angeles	California
United States	USC / Norris Comprehensive Cancer Center	Los Angeles	California
United States	Marshfield Medical Center-Marshfield	Marshfield	Wisconsin
United States	Carle Physician Group-Mattoon/Charleston	Mattoon	Illinois
United States	Loyola University Medical Center	Maywood	Illinois
United States	Rogue Valley Medical Center	Medford	Oregon
United States	Saint Luke's Cancer Institute - Meridian	Meridian	Idaho
United States	East Jefferson General Hospital	Metairie	Louisiana
United States	LSU Healthcare Network / Metairie Multi-Specialty Clinic	Metairie	Louisiana
United States	Memorial Sloan Kettering Monmouth	Middletown	New Jersey
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Marshfield Clinic-Minocqua Center	Minocqua	Wisconsin
United States	University of South Alabama Mitchell Cancer Institute	Mobile	Alabama
United States	West Virginia University Healthcare	Morgantown	West Virginia
United States	Good Samaritan Regional Health Center	Mount Vernon	Illinois
United States	Saint Alphonsus Medical Center-Nampa	Nampa	Idaho
United States	Saint Luke's Cancer Institute - Nampa	Nampa	Idaho
United States	Smilow Cancer Center/Yale-New Haven Hospital	New Haven	Connecticut
United States	Yale University	New Haven	Connecticut
United States	Louisiana State University Health Science Center	New Orleans	Louisiana
United States	Ochsner Medical Center Jefferson	New Orleans	Louisiana
United States	University Medical Center New Orleans	New Orleans	Louisiana
United States	Laura and Isaac Perlmutter Cancer Center at NYU Langone	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Henry Ford Medical Center-Columbus	Novi	Michigan
United States	Cancer Care Center of O'Fallon	O'Fallon	Illinois
United States	Kaiser Permanente-Oakland	Oakland	California
United States	Mercy Hospital Oklahoma City	Oklahoma City	Oklahoma
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Saint Alphonsus Medical Center-Ontario	Ontario	Oregon
United States	UC Irvine Health/Chao Family Comprehensive Cancer Center	Orange	California
United States	Stanford Cancer Institute Palo Alto	Palo Alto	California
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	Mayo Clinic Hospital in Arizona	Phoenix	Arizona
United States	Oregon Health and Science University	Portland	Oregon
United States	Portland VA Medical Center	Portland	Oregon
United States	Renown Regional Medical Center	Reno	Nevada
United States	Marshfield Medical Center-Rice Lake	Rice Lake	Wisconsin
United States	University of Rochester	Rochester	New York
United States	Kaiser Permanente-South Sacramento	Sacramento	California
United States	Mercy Hospital Saint Louis	Saint Louis	Missouri
United States	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah
United States	Audie L Murphy VA Hospital	San Antonio	Texas
United States	University Hospital	San Antonio	Texas
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	UCSF Medical Center-Mission Bay	San Francisco	California
United States	Mayo Clinic in Arizona	Scottsdale	Arizona
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	University of Washington Medical Center - Montlake	Seattle	Washington
United States	Prisma Health Cancer Institute - Seneca	Seneca	South Carolina
United States	LSU Health Sciences Center at Shreveport	Shreveport	Louisiana
United States	South Jordan Health Center	South Jordan	Utah
United States	Memorial Medical Center	Springfield	Illinois
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	Southern Illinois University School of Medicine	Springfield	Illinois
United States	Springfield Clinic	Springfield	Illinois
United States	Marshfield Clinic Stevens Point Center	Stevens Point	Wisconsin
United States	State University of New York Upstate Medical University	Syracuse	New York
United States	Madigan Army Medical Center	Tacoma	Washington
United States	Moffitt Cancer Center	Tampa	Florida
United States	Moffitt Cancer Center - McKinley Campus	Tampa	Florida
United States	Saint Luke's Cancer Institute - Twin Falls	Twin Falls	Idaho
United States	Memorial Sloan Kettering Nassau	Uniondale	New York
United States	Carle Cancer Center	Urbana	Illinois
United States	The Carle Foundation Hospital	Urbana	Illinois
United States	Kaiser Permanente-Vallejo	Vallejo	California
United States	Kaiser Permanente-Walnut Creek	Walnut Creek	California
United States	Saint John Macomb-Oakland Hospital	Warren	Michigan
United States	George Washington University Medical Center	Washington	District of Columbia
United States	MedStar Washington Hospital Center	Washington	District of Columbia
United States	Marshfield Clinic-Wausau Center	Wausau	Wisconsin
United States	Henry Ford West Bloomfield Hospital	West Bloomfield	Michigan
United States	Marshfield Medical Center - Weston	Weston	Wisconsin
United States	University of Kansas Hospital-Westwood Cancer Center	Westwood	Kansas
United States	Marshfield Clinic - Wisconsin Rapids Center	Wisconsin Rapids	Wisconsin

Sponsors (2)

Lead Sponsor	Collaborator
SWOG Cancer Research Network	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	TTHGR for Arm I compared to Arm II	Time to High Grade Recurrence	Time from randomization to first high grade recurrence assessed up to 5 years
Primary	TTHGR for Arm II compared to Arm III	Time to High Grade Recurrence	Time from randomization to first high grade recurrence assessed up to 5 years
Secondary	Disease free rates	Rates of patients who are disease free at six months versus not	At 6 months