Combining Immunotherapy and Radiation Therapy to Help Patients Avoid Bladder Removal After Treatment Shrinks Muscle Invasive Bladder Cancer, BRIGHT Trial
Purpose
This phase II trial tests the effect of giving pembrolizumab in combination with radiation therapy after chemotherapy in preventing surgery to remove the bladder in patients with muscle invasive bladder cancer. Standard of care therapy includes chemotherapy before surgery (neoadjuvant) to shrink or get rid of the tumor. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. Photon beam radiation therapy is a type of radiation therapy that uses x-rays or gamma rays that come from a special machine called a linear accelerator. The radiation dose is delivered at the surface of the body and goes into the tumor and through the body. Giving pembrolizumab in combination with radiation therapy after neoadjuvant chemotherapy may help prevent surgical removal of the bladder in patients with muscle invasive bladder cancer.
Conditions
- Muscle Invasive Bladder Urothelial Carcinoma
- Stage II Bladder Cancer AJCC v8
- Stage IIIA Bladder Cancer AJCC v8
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Criteria
Inclusion Criteria:
- Participants must have histologic evidence of cT2-T4aN0M0 muscle invasive urothelial
carcinoma of the bladder within 180 days prior to starting neoadjuvant therapy (NAT)
- Participants must have had CT chest/abdomen/pelvis (C/A/P), MRI C/A/P or PET within
60 days prior to starting NAT to determine cT2-T4aN0M0
- Participants must have undergone TURBT with biopsy of areas of prior disease and
systematic biopsies (left and right lateral, dome, posterior wall and trigone) and
radiologic staging showing clinically T0-T1 disease within 60 days after the last
dose of NAT. At least 4 out of 5 systematic biopsies must be performed
- NOTE: This TURBT must be within 90 days prior to registration. Registration
must be within 90 days after the last dose of NAT
- Participants must have imaging of the chest, abdomen, and pelvis performed using CT
or MRI preferably with contrast. Fludeoxyglucose F-18 (FDG) PET-CT can also be used
for staging. If FDG PET-CT is used, then it is at the discretion of the investigator
if they want to additionally obtain diagnostic CT or MRI with contrast within 60
days after the last dose of NAT
- Participants with lymph nodes ≥ 1.0 cm in the shortest cross-sectional diameter on
imaging (CT or MRI of abdomen and pelvis) after completion of NAT must have a PET-CT
within 70 days prior to registration. A biopsy in the setting of negative PET-CT is
not required unless there is strong clinical suspicion for nodal involvement with
tumor. Participants with a positive PET are deemed ineligible unless a biopsy is
performed and shows no evidence of tumor involvement
- NOTE: For questions regarding the above eligibility criteria, please contact
the study chairs in addition to the Southwest Oncology Group (SWOG) Statistics
and Data Management Center (SDMC)
- Participants must not have evidence of ≥ T2, or N1-3, or M1 disease after NAT
- Participants must not have the presence of small cell, neuroendocrine carcinoma,
plasmacytoid variants on any pathology
- Participants must not have had urothelial carcinoma or histological variant at any
site outside of the urinary bladder within 24 months prior to registration except
Ta/T1/carcinoma in situ (CIS) of the upper urinary tract, including renal pelvis or
ureter if the participant underwent complete nephroureterectomy
- NOTE: Participants with mixed variant histology will be eligible for the trial
if the majority (> 50%) of the tumor is urothelial cell carcinoma
- Participants will be allowed to continue PD-1/L-1 inhibitor therapy received as part
of standard of care neoadjuvant therapy while they undergo pre-registration
assessments (TURBT and imaging)
- Participants must have received at least 3 and no more than 6 cycles of Food and
Drug Administration (FDA) approved NAT for MIBC. These include cisplatin-based
combination chemotherapy (e.g. cisplatin and gemcitabine [GC] with or without
PD-1/L1 inhibitors) dose dense or accelerated methotrexate, vinblastine, doxorubicin
and cisplatin (MVAC) or enfortumab vedotin with PD-1/L1 inhibitor
- Participants must not have had anti-PD-1, anti PD-L1, anti PD-L2 or anti-CTLA4
antibody, any other antibody or drug targeting T-cell co-stimulation, enfortumab
vedotin, or any other drug targeting nectin-4 other than for neoadjuvant treatment
for MIBC
- NOTE: Prior intravesical immunotherapy or chemotherapy for non-muscle invasive
disease is allowed
- Participants must not have had prior pelvic radiotherapy
- Participants must not have received a live attenuated vaccination within 28 days
prior to registration
- Participants with conditions requiring immunosuppressive doses of steroids (> 10
mg/day of prednisone or equivalent) or other immunosuppressive medications must not
be taking steroids at time of trial registration
- Participants must be ≥ 18 years old at the time of registration
- Participants must have Zubrod performance status of 0-2
- Participants must have a complete medical history and physical exam within 28 days
prior to registration
- Leukocytes ≥ 3 x 10^3/uL (within 28 days prior to registration)
- Absolute neutrophil count ≥ 1.5 x 10^3/uL (within 28 days prior to registration)
- Platelets ≥ 100 x 10^3/uL (within 28 days prior to registration)
- Total bilirubin ≤ institutional upper limit of normal (ULN) unless history of
Gilbert's disease (within 28 days prior to registration)
- Participants with history of Gilbert's disease must have total bilirubin ≤ 5 x
institutional ULN
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 3 x institutional
ULN (within 28 days prior to registration)
- Participants must have a creatinine ≤ the institutional (I)ULN OR measured OR
calculated creatinine clearance ≥ 40 mL/min using the following Cockcroft-Gault
Formula. This specimen must have been drawn and processed within 28 days prior to
registration
- Participants with known history or current symptoms of cardiac disease, or history
of treatment with cardiotoxic agents, should have a clinical risk assessment of
cardiac function using the New York Heart Association Functional Classification. To
be eligible for this trial, patients should be class II or better
- Participants with a history of human immunodeficiency virus (HIV)-infection must be
on effective anti-retroviral therapy at registration and have undetectable viral
load test on the most recent test results obtained within 6 months prior to
registration
- For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV
viral load must be undetectable on suppressive therapy, if indicated
- Participants with a history of hepatitis C virus (HCV) infection must have been
treated and cured (defined as undetectable HCV viral load)
- Participants must not have a prior or concurrent malignancy whose natural history or
treatment (in the opinion of the treating physician) has the potential to interfere
with the safety or efficacy assessment of the investigational regimen
- Participants must not be pregnant or nursing (nursing includes breast milk fed to an
infant by any means, including from the breast, milk expressed by hand, or pumped).
Individuals who are of reproductive potential must have agreed to use an effective
contraceptive method with details provided as a part of the consent process. A
person who has had menses at any time in the preceding 12 consecutive months or who
has semen likely to contain sperm is considered to be of "reproductive potential."
In addition to routine contraceptive methods, "effective contraception" also
includes refraining from sexual activity that might result in pregnancy and surgery
intended to prevent pregnancy (or with a side-effect of pregnancy prevention)
including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion,
and vasectomy with testing showing no sperm in the semen
- Participants must be offered the opportunity to participate in specimen banking
- Participants who can complete the PRO-CTCAE questionnaire in English or Spanish will
be offered the opportunity to participate in the optional patient-reported outcome
study
- NOTE: As a part of the Oncology Patient Enrollment Network (OPEN) registration
process the treating institution's identity is provided in order to ensure that the
current (within 365 days) date of institutional review board approval for this study
has been entered in the system
- Participants must be informed of the investigational nature of this study and
must sign and give informed consent in accordance with institutional and
federal guidelines
- For participants with impaired decision-making capabilities, legally authorized
representatives may sign and give informed consent on behalf of study
participants in accordance with applicable federal, local, and central
institutional review board (CIRB) regulations
Study Design
- Phase
- Phase 2
- Study Type
- Interventional
- Allocation
- N/A
- Intervention Model
- Single Group Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Treatment (photon beam RT, pembrolizumab) |
Patients undergo photon beam RT QD on Monday-Friday for up to 20 treatments and receive pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for up to 18 cycles (for a total of 12 months, including NAT) in the absence of disease progression or unacceptable toxicity. Patients also undergo TURBT with tissue sample collection at pre-registration and CT, MRI or PET, cystoscopy, and urine and blood sample collection throughout the study. |
|
Recruiting Locations
Birmingham, Alabama 35233
Gilbert, Arizona 85234
Site Public Contact
602-747-9738
Phoenix, Arizona 85054
Site Public Contact
855-776-0015
Fayetteville, Arkansas 72703
Rogers, Arkansas 72758
Springdale, Arkansas 72762
Beverly Hills, California 90211
Corona, California 92882
Duarte, California 91010
Irvine, California 92618
Site Public Contact
877-467-3411
Lancaster, California 93534
Los Angeles, California 90033
Los Angeles, California 90033
Site Public Contact
323-865-0451
Los Angeles, California 90048
Sacramento, California 95817
Site Public Contact
916-734-3089
South Pasadena, California 91030
Tarzana, California 91356
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818-981-3818
Upland, California 91786
Aurora, Colorado 80045
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720-848-0650
Edwards, Colorado 81632
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970-569-7429
Fort Collins, Colorado 80524
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970-297-6150
Fort Collins, Colorado 80528
Highlands Ranch, Colorado 80129
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720-848-0650
Lone Tree, Colorado 80124
Loveland, Colorado 80538
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970-203-7083
Ruskin, Florida 33570
Tampa, Florida 33607
Tampa, Florida 33612
Tampa, Florida 33612
Wesley Chapel, Florida 33544
Newnan, Georgia 30265
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770-400-6629
Aurora, Illinois 60504
Bloomington, Illinois 61701
Bloomington, Illinois 61704
Canton, Illinois 61520
Carthage, Illinois 62321
Chicago, Illinois 60611
Danville, Illinois 61832
Decatur, Illinois 62526
Decatur, Illinois 62526
DeKalb, Illinois 60115
Effingham, Illinois 62401
Eureka, Illinois 61530
Evanston, Illinois 60201
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847-570-2109
Galesburg, Illinois 61401
Geneva, Illinois 60134
Glenview, Illinois 60026
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847-570-2109
Glenview, Illinois 60026
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312-695-1102
Grayslake, Illinois 60030
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312-695-1102
Highland Park, Illinois 60035
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847-570-2109
Kewanee, Illinois 61443
Lake Forest, Illinois 60045
Macomb, Illinois 61455
Mattoon, Illinois 61938
O'Fallon, Illinois 62269
O'Fallon, Illinois 62269
Oak Brook, Illinois 60523
Orland Park, Illinois 60462
Ottawa, Illinois 61350
Pekin, Illinois 61554
Peoria, Illinois 61615
Peoria, Illinois 61615
Peoria, Illinois 61637
Peru, Illinois 61354
Princeton, Illinois 61356
Springfield, Illinois 62702
Site Public Contact
217-545-7929
Springfield, Illinois 62702
Site Public Contact
800-444-7541
Springfield, Illinois 62781
Urbana, Illinois 61801
Warrenville, Illinois 60555
Washington, Illinois 61571
Ames, Iowa 50010
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515-956-4132
Ames, Iowa 50010
Ankeny, Iowa 50023
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515-241-3305
Clive, Iowa 50325
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515-241-3305
Clive, Iowa 50325
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515-241-3305
Des Moines, Iowa 50309
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515-241-6727
Des Moines, Iowa 50309
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515-241-3305
Des Moines, Iowa 50314
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515-241-3305
Des Moines, Iowa 50314
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515-241-3305
Waukee, Iowa 50263
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515-241-3305
West Des Moines, Iowa 50266
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515-875-9815
Lexington, Kentucky 40536
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859-257-3379
Louisville, Kentucky 40202
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502-562-3429
Louisville, Kentucky 40245
New Orleans, Louisiana 70112
New Orleans, Louisiana 70121
Boston, Massachusetts 02111
Boston, Massachusetts 02215
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877-442-3324
Worcester, Massachusetts 01655
Bemidji, Minnesota 56601
Edina, Minnesota 55435
Saint Louis Park, Minnesota 55416
Jackson, Mississippi 39216
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601-815-6700
Cape Girardeau, Missouri 63703
Billings, Montana 59101
Lebanon, New Hampshire 03756
Cherry Hill, New Jersey 08002
Flemington, New Jersey 08822
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908-237-2330
Jersey City, New Jersey 07302
Livingston, New Jersey 07039
New Brunswick, New Jersey 08903
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732-235-7356
Sewell, New Jersey 08080
Flushing, New York 11355
New York, New York 10065
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212-746-1848
Stony Brook, New York 11794
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800-862-2215
Fargo, North Dakota 58122
Fargo, North Dakota 58122
Cincinnati, Ohio 45219
West Chester, Ohio 45069
Oklahoma City, Oklahoma 73104
Philadelphia, Pennsylvania 19104
Philadelphia, Pennsylvania 19107
Willow Grove, Pennsylvania 19090
Sioux Falls, South Dakota 57104
Sioux Falls, South Dakota 57117-5134
Germantown, Tennessee 38138
Dallas, Texas 75235
Dallas, Texas 75237
Dallas, Texas 75390
Fort Worth, Texas 76104
Houston, Texas 77030
Richardson, Texas 75080
San Antonio, Texas 78229
Temple, Texas 76508
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254-724-5407
Salt Lake City, Utah 84112
Saint Johnsbury, Vermont 05819
Richmond, Virginia 23235
Richmond, Virginia 23298
Seattle, Washington 98122
Morgantown, West Virginia 26506
Parkersburg, West Virginia 26101
Appleton, Wisconsin 54915
Brookfield, Wisconsin 53045
Chilton, Wisconsin 53014
Franklin, Wisconsin 53132
Green Bay, Wisconsin 54301
Green Bay, Wisconsin 54303
Mequon, Wisconsin 53097
Milwaukee, Wisconsin 53211
Oconto Falls, Wisconsin 54154
Oshkosh, Wisconsin 54904
Racine, Wisconsin 53405
Sheboygan, Wisconsin 53081
Sturgeon Bay, Wisconsin 54235-1495
Wauwatosa, Wisconsin 53226
More Details
- Status
- Recruiting
- Sponsor
- National Cancer Institute (NCI)
Study Contact
Detailed Description
PRIMARY OBJECTIVE: I. To evaluate whether 3-year bladder intact event-free survival (BI-EFS) is at least 70% in participants with clinically T0-clinically T1 without multifocal carcinoma in situ (CIS) following neoadjuvant therapy (NAT) for muscle-invasive bladder cancer (MIBC) who receive radiotherapy (RT) + pembrolizumab (MK-3475). SECONDARY OBJECTIVES: I. To estimate BI-EFS in participants who receive RT + pembrolizumab (MK-3475). II. To estimate local muscle invasive recurrence-free survival in participants who receive RT+ pembrolizumab (MK-3475). III. To estimate the metastasis-free survival (MFS) in participants who receive RT+ pembrolizumab (MK-3475). IV. To estimate the overall survival (OS) in participants who receive RT + pembrolizumab (MK-3475). V. To estimate the rate of salvage cystectomy in participants who receive RT+ pembrolizumab (MK-3475). VI. To evaluate the frequency and severity of toxicities in participants who receive RT + pembrolizumab (MK-3475). PATIENT REPORTED OUTCOMES (PRO)-COMMON TERMINOLOGY CRITERIA FOR ADVERSE EVENTS (CTCAE) OBJECTIVE: I. To evaluate participant-reported symptoms using selected items from Gastrointestinal, Genitourinary and sexual function domains of the PRO-CTCAE, with the goal of characterizing the frequency, severity, and interference of treatment-related symptoms. BANKING OBJECTIVE: I. To bank specimens for future correlative studies. OUTLINE: Patients undergo photon beam RT once daily (QD) on Monday-Friday for up to 20 treatments and receive pembrolizumab intravenously (IV) over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for up to 18 cycles (for a total of 12 months, including NAT) in the absence of disease progression or unacceptable toxicity. Patients also undergo transurethral resection of bladder tumor (TURBT) with tissue sample collection at pre-registration and computed tomography (CT), magnetic resonance imaging (MRI) or positron emission tomography (PET), cystoscopy, and urine and blood sample collection throughout the study. After completion of study treatment, patients are followed every 26 weeks until year 2 and then every 52 weeks up to year 5.