Different Versions of BCG with or without Vaccine Therapy in Treating Patients with High Grade Bladder Cancer That Is Not Muscle Invasive
- Patients must have histologically proven Ta, carcinoma in situ (CIS) or T1 stage urothelial cell carcinoma of the bladder within 90 days prior to 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 nodal involvement or 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
- No other prior non-bladder 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 or intradermal BCG
- 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
- Patients must not have known history of tuberculosis
- Patients must be negative for prior Tuberculosis infection as determined by a negative PPD test; if PPD is not available, then a negative interferon gamma release assay (IGRA) may be used; the PPD or IGRA test results must be obtained 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); for PPD readings done outside of 48-72 hour window, patients must have PPD test and reading repeated to confirm eligibility; IGRA positive is defined by the laboratory interpretation or using the package insert cut-off values; any IGRA approved by the Food and Drug Administration (FDA) is allowed, including the QuantiFERON–TB Gold In-Tube test (QFT–GIT) or the T–SPOT TB test (T–Spot)
- Patients must be >= 18 years of age
- Prestudy history and physical must be obtained within 90 days prior to registration; patients must have a complete blood count (CBC) and basic metabolic panel including creatinine, potassium, chloride, blood urea nitrogen (BUN), carbon dioxide (CO2) and glucose within 28 days prior to registration
- Patients must not be pregnant or nursing as the use of intravesical BCG is not recommended during pregnancy; 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
- Patients who can complete patient-reported outcome (PRO) forms in English or Spanish must complete the baseline Bladder Cancer Index, European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-Core (C) 30, American Urological Association Symptom Score (AUASS), and Cancer Patient Tobacco Use Questionnaire forms
District of Columbia
Salt Lake City
I. To compare whether time to high-grade recurrence (TTHGR) for patients with BCG-naive, non-muscle invasive bladder cancer (NMIBC) receiving BCG Tokyo-172 strain solution (Tokyo-172 BCG) (Arm II) is non-inferior to patients receiving BCG solution (BCG LIVE [TICE BCG]) (Arm I).
II. To test whether TTHGR for patients with BCG-naive, NMIBC receiving intradermal BCG Tokyo-172 strain vaccine (Tokyo-172 BCG vaccination) followed by intravesical Tokyo-172 BCG instillation (Arm III) is superior to patients receiving intravesical Tokyo-172 BCG instillation without prior intradermal BCG vaccination (Arm II).
I. To compare time to recurrence (TTR) with any-grade (AG) bladder cancer between:
Ia. patients receiving Tokyo-172 versus BCG LIVE (TICE BCG) strain.
Ia. Patients receiving intradermal + intravesical versus intravesical only Tokyo-172 BCG.
II. To compare progression-free survival (PFS) between:
IIa. Patients receiving Tokyo-172 versus BCG LIVE (TICE BCG) strain.
IIa. Patients receiving intradermal + intravesical versus intravesical only Tokyo-172 BCG.
III. To estimate the complete response (CR) rate for carcinoma in situ (CIS) patients at 6 months in patients receiving intravesical versus intravesical only Tokyo-172 BCG (Arms II & III will be evaluated separately).
IV. To evaluate the duration of CR by treatment arm for patients with CIS who have a CR at 6 months.
V. To test whether TTHGR for patients with BCG-naive, NMIBC receiving intradermal Tokyo-172 BCG vaccination followed by intravesical Tokyo-172 BCG instillation is superior to patients receiving intravesical TICE BCG strain.
PRIMARY TRANSLATIONAL RESEARCH 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 measured prior to weeks 1, 3 and 6 BCG instillation 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.
IV. To assess whether changes in pre-BCG extracellular vesicle profiles in urine and blood from week 1 to week 3 vary by treatment arm and whether these changes are prognostic for TTHGR.
PATIENT REPORTED OUTCOMES OBJECTIVES:
I. To compare the change (baseline to 6 month) in patient-reported bladder cancer-specific quality of life between TICE and Tokyo BCG strains.
II. To compare the change (baseline to 6 month) in patient-reported quality of life between priming and no priming.
III. To test the hypothesis that changes in urinary symptoms during BCG treatment predict time to high-grade recurrence (TTHGR).
IV. To evaluate whether smoking status is associated with time TTHGR, and whether the efficacy of BCG strain (Tice versus [vs.] Tokyo) and BCG priming is modified by measures of smoking exposure.
V. To estimate adverse event profiles for each of the three treatment arms by smoking status.
OUTLINE: Patients are randomized to 1 of 3 treatment arms.
INDUCTION: Patients receive BCG solution intravesically once a week for 6 weeks.
MAINTENANCE: Patients receive BCG solution intravesically once a week for 3 consecutive weeks at months 3, 6, 12, 18, 24, 30, and 36 for 21 doses.
INDUCTION: Patients receive BCG Tokyo-172 strain solution intravesically once a week for 6 weeks.
MAINTENANCE: Patients receive BCG Tokyo-172 strain solution intravesically once a week for 3 consecutive weeks at months 3, 6, 12, 18, 24, 30, and 36 for 21 doses.
PRIME: Patients receive BCG Tokyo-172 strain vaccine once intradermally (ID).
INDUCTION: Within 21 days, patients receive BCG Tokyo-172 strain solution as in Arm II.
MAINTENANCE: Patients receive BCG Tokyo-172 strain solution as in Arm II.
After completion of study treatment, patients are followed up for 5 years.
Trial Phase Phase III
Trial Type Treatment
Robert Scott Svatek
- Primary ID S1602
- Secondary IDs NCI-2016-00451
- Clinicaltrials.gov ID NCT03091660