Bladder Cancer Clinical Trial

Testing the Addition of an Anti-Cancer Immunotherapy Drug, Avelumab, to Gemcitabine and Carboplatin Chemotherapy Prior to Surgery in Muscle Invasive Urinary Tract Cancer vs. Surgery Alone in Patients Who Are Not Able to Receive Cisplatin Therapy (SWOG GAP TRIAL)

Summary

This phase II trial studies the effect of avelumab, gemcitabine and carboplatin before surgery compared with surgery alone in treating patients with muscle invasive bladder or upper urinary tract cancer who are not able to receive cisplatin therapy. Immunotherapy with monoclonal antibodies, such as avelumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as gemcitabine and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving avelumab together with gemcitabine and carboplatin before surgery may work better in lowering the chance of muscle invasive urinary tract cancer growing or spreading, in patients who cannot receive cisplatin therapy compared to surgery alone.

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Full Description

PRIMARY OBJECTIVE:

I. To compare pathologic complete response (pCR, pT0N0) with avelumab plus gemcitabine and carboplatin (AGCa) versus (vs.) no neoadjuvant therapy preceding protocol surgery for muscle-invasive bladder cancer or upper tract urothelial carcinoma (MIBC/UTUC) for participants who are ineligible for cisplatin-based chemotherapy.

SECONDARY OBJECTIVES:

I. To evaluate toxicities with AGCa, and to compare resectability rates and surgical complications by arm in this population.

II. To compare event-free survival (EFS) with AGCa versus no neoadjuvant therapy in this population.

III. To compare overall survival (OS) with AGCa versus no neoadjuvant therapy preceding surgery in this population.

IV. To compare pathologic complete response (pCR, pT0N0) with avelumab plus gemcitabine and carboplatin (AGCa) vs. no neoadjuvant therapy preceding protocol surgery in the subset of participants who received at least 2 cycles of neoadjuvant therapy in Arm A.

BANKING OBJECTIVE:

I. To bank tumor tissue, blood, and urine for future correlative genomic, transcriptomic, and proteomic studies to discover molecular signatures associated with pCR and resistance.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients receive avelumab intravenously (IV) over 60 minutes on day 1. Treatment repeats every 14 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for up 4 in the absence of disease progression or unacceptable toxicity. Within 4-8 weeks after final systemic therapy, patients undergo standard of care surgery.

ARM B: Patients undergo standard of care surgery.

After completion of study treatment, patients are followed up every 12 weeks for years 1-2, every 6 months for year 3, then annually in years 4-5.

View Eligibility Criteria

Eligibility Criteria

Inclusion Criteria:

Participants must have one of the following:

Histologically documented muscle-invasive bladder carcinoma (MIBC) from transurethral resection of bladder tumor (TURBT) within 56 days prior to registration
Histologically confirmed high grade upper tract urothelial carcinoma (UTUC) within 56 days prior to registration, with invasion confirmed by either a mass on cross-sectional imaging or a tumor directly visualized during upper urinary tract endoscopy within 56 days prior to registration
Participants diagnosed with mixed urothelial carcinoma and variant histology within 56 days prior to registration may be eligible if the majority (> 50%) of the tumor consists of urothelial carcinoma. Participants with pure non-urothelial variant histologies or any small cell histology are not eligible
Participants must have clinical stage T2-T4aN0M0 bladder or upper tract cancer confirmed by radiologic staging (computed tomography [CT] scan/magnetic resonance imaging [MRI] abdomen and pelvis, and CT scan/x-ray of the chest) within 56 days prior to registration
Participants must have a bone scan within 56 days prior to registration if they have bone pain or elevated serum alkaline phosphatase
Participants must have a bimanual examination under anesthesia within 56 days prior to registration
Participants must not have received prior systemic chemotherapy, immunotherapy or radiotherapy for the treatment of muscle invasive bladder cancer (MIBC) or upper tract urothelial carcinoma (UTUC). Other prior pelvic radiotherapy is allowed if it does not preclude surgery (radical cystectomy, nephroureterectomy or ureterectomy, based on location of primary tumor). Prior intravesical therapy is allowed
Participants must not have received immunosuppressive medication within 14 days prior to registration, with the exception of 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
Participants must be >= 18 years of age
Participants must have Zubrod performance status 0-2
Participants must have history and physical examination within 28 days prior to registration
Participants must be surgical candidates as deemed by the local site oncologic surgeon within 28 days prior to registration. This must be clearly documented
Participants must have a serum creatinine =< the institutional upper limit of normal (IULN) OR measured OR calculated creatinine clearance >= 30 mL/min using the Crockroft-Gault Formula. This specimen must have been drawn and processed within 28 days prior to registration

Participants must be deemed cisplatin-ineligible based on greater than or equal to 1 of the following:

Zubrod performance status = 2
Creatinine clearance (calculated by Crockroft-Gault formula or measured) 30 to < 60 ml/min,
Neuropathy > grade 1
Hearing loss > grade 1
Congestive heart failure > grade 2
Hemoglobin >= 9.0 g/dL (within 28 days prior to registration)
Absolute neutrophil count >= 1,500/mcL (within 28 days prior to registration)
Platelets >= 100,000/mcL (within 28 days prior to registration)
Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (within 28 days prior to registration)
Aspartate aminotransferase (AST) =< 2.5 x institutional ULN (within 28 days prior to registration)
Alanine aminotransferase (ALT) =< 2.5 x institutional ULN (within 28 days prior to registration)
Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, must have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification and be class 2B or better
Participants with known human immunodeficiency virus (HIV) must be on effective anti-retroviral therapy and have undetectable viral load at their most recent viral load test and within 6 months prior to registration

Exclusion Criteria:

Participant must not have any other prior malignancy except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, prostate cancer Gleason score =< 3+4 in active surveillance, adequately treated stage I or II cancer from which the participant is currently in complete remission, or any other cancer from which the participant has been disease free for two years
Participants must not be pregnant or nursing due to the risk of harm to a fetus or nursing infant. Women/men of reproductive potential must have a negative serum or urine pregnancy test within 28 days prior to registration and 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 participant 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
Participants must not have a history of active primary immunodeficiency
Participants must not have a history of or active autoimmune or inflammatory disorder, with the exception of vitiligo, alopecia, hypothyroidism (stable on hormone replacement), or chronic skin condition that does not require systemic therapy

Study is for people with:

Bladder Cancer

Phase:

Phase 2

Estimated Enrollment:

196

Study ID:

NCT04871529

Recruitment Status:

Suspended

Sponsor:

SWOG Cancer Research Network

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There are 78 Locations for this study

See Locations Near You

University of Colorado Hospital
Aurora Colorado, 80045, United States
UCHealth Highlands Ranch Hospital
Highlands Ranch Colorado, 80129, United States
AdventHealth Orlando
Orlando Florida, 32803, United States
Pali Momi Medical Center
'Aiea Hawaii, 96701, United States
Queen's Medical Center
Honolulu Hawaii, 96813, United States
Straub Clinic and Hospital
Honolulu Hawaii, 96813, United States
Saint Anthony's Health
Alton Illinois, 62002, United States
Illinois CancerCare-Bloomington
Bloomington Illinois, 61704, United States
Illinois CancerCare-Canton
Canton Illinois, 61520, United States
Illinois CancerCare-Carthage
Carthage Illinois, 62321, United States
Northwestern University
Chicago Illinois, 60611, United States
University of Illinois
Chicago Illinois, 60612, United States
Carle at The Riverfront
Danville Illinois, 61832, United States
Cancer Care Specialists of Illinois - Decatur
Decatur Illinois, 62526, United States
Decatur Memorial Hospital
Decatur Illinois, 62526, United States
Northwestern Medicine Cancer Center Kishwaukee
DeKalb Illinois, 60115, United States
Illinois CancerCare-Dixon
Dixon Illinois, 61021, United States
Carle Physician Group-Effingham
Effingham Illinois, 62401, United States
Crossroads Cancer Center
Effingham Illinois, 62401, United States
Illinois CancerCare-Eureka
Eureka Illinois, 61530, United States
NorthShore University HealthSystem-Evanston Hospital
Evanston Illinois, 60201, United States
Illinois CancerCare-Galesburg
Galesburg Illinois, 61401, United States
Northwestern Medicine Cancer Center Delnor
Geneva Illinois, 60134, United States
NorthShore University HealthSystem-Glenbrook Hospital
Glenview Illinois, 60026, United States
NorthShore University HealthSystem-Highland Park Hospital
Highland Park Illinois, 60035, United States
Illinois CancerCare-Kewanee Clinic
Kewanee Illinois, 61443, United States
Northwestern Medicine Lake Forest Hospital
Lake Forest Illinois, 60045, United States
Illinois CancerCare-Macomb
Macomb Illinois, 61455, United States
Carle Physician Group-Mattoon/Charleston
Mattoon Illinois, 61938, United States
Cancer Care Center of O'Fallon
O'Fallon Illinois, 62269, United States
Illinois CancerCare-Ottawa Clinic
Ottawa Illinois, 61350, United States
Illinois CancerCare-Pekin
Pekin Illinois, 61554, United States
Illinois CancerCare-Peoria
Peoria Illinois, 61615, United States
Illinois CancerCare-Peru
Peru Illinois, 61354, United States
Illinois CancerCare-Princeton
Princeton Illinois, 61356, United States
Southern Illinois University School of Medicine
Springfield Illinois, 62702, United States
Springfield Clinic
Springfield Illinois, 62702, United States
Memorial Medical Center
Springfield Illinois, 62781, United States
Carle Cancer Center
Urbana Illinois, 61801, United States
Northwestern Medicine Cancer Center Warrenville
Warrenville Illinois, 60555, United States
Illinois CancerCare - Washington
Washington Illinois, 61571, United States
Mary Greeley Medical Center
Ames Iowa, 50010, United States
McFarland Clinic - Ames
Ames Iowa, 50010, United States
McFarland Clinic - Boone
Boone Iowa, 50036, United States
McFarland Clinic - Trinity Cancer Center
Fort Dodge Iowa, 50501, United States
McFarland Clinic - Jefferson
Jefferson Iowa, 50129, United States
McFarland Clinic - Marshalltown
Marshalltown Iowa, 50158, United States
East Jefferson General Hospital
Metairie Louisiana, 70006, United States
LSU Healthcare Network / Metairie Multi-Specialty Clinic
Metairie Louisiana, 70006, United States
Saint Joseph Mercy Hospital
Ann Arbor Michigan, 48106, United States
Saint Joseph Mercy Brighton
Brighton Michigan, 48114, United States
Trinity Health IHA Medical Group Hematology Oncology - Brighton
Brighton Michigan, 48114, United States
Saint Joseph Mercy Canton
Canton Michigan, 48188, United States
Trinity Health IHA Medical Group Hematology Oncology - Canton
Canton Michigan, 48188, United States
Saint Joseph Mercy Chelsea
Chelsea Michigan, 48118, United States
Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
Chelsea Michigan, 48118, United States
Hematology Oncology Consultants-Clarkston
Clarkston Michigan, 48346, United States
Newland Medical Associates-Clarkston
Clarkston Michigan, 48346, United States
Genesee Cancer and Blood Disease Treatment Center
Flint Michigan, 48503, United States
Genesee Hematology Oncology PC
Flint Michigan, 48503, United States
Genesys Hurley Cancer Institute
Flint Michigan, 48503, United States
Trinity Health Saint Mary Mercy Livonia Hospital
Livonia Michigan, 48154, United States
Newland Medical Associates-Pontiac
Pontiac Michigan, 48341, United States
Saint Joseph Mercy Oakland
Pontiac Michigan, 48341, United States
Ascension Saint Mary's Hospital
Saginaw Michigan, 48601, United States
Oncology Hematology Associates of Saginaw Valley PC
Saginaw Michigan, 48604, United States
Ascension Saint Joseph Hospital
Tawas City Michigan, 48764, United States
Huron Gastroenterology PC
Ypsilanti Michigan, 48106, United States
Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
Ypsilanti Michigan, 48197, United States
Mercy Hospital
Coon Rapids Minnesota, 55433, United States
Saint Francis Medical Center
Cape Girardeau Missouri, 63703, United States
Parkland Health Center - Farmington
Farmington Missouri, 63640, United States
Missouri Baptist Medical Center
Saint Louis Missouri, 63131, United States
Sainte Genevieve County Memorial Hospital
Sainte Genevieve Missouri, 63670, United States
Missouri Baptist Sullivan Hospital
Sullivan Missouri, 63080, United States
Missouri Baptist Outpatient Center-Sunset Hills
Sunset Hills Missouri, 63127, United States
Cleveland Clinic Cancer Center/Fairview Hospital
Cleveland Ohio, 44111, United States
Cleveland Clinic Foundation
Cleveland Ohio, 44195, United States
Cleveland Clinic Cancer Center Mansfield
Mansfield Ohio, 44906, United States
Hillcrest Hospital Cancer Center
Mayfield Heights Ohio, 44124, United States
North Coast Cancer Care
Sandusky Ohio, 44870, United States
ProMedica Flower Hospital
Sylvania Ohio, 43560, United States
Cleveland Clinic Wooster Family Health and Surgery Center
Wooster Ohio, 44691, United States
University of Oklahoma Health Sciences Center
Oklahoma City Oklahoma, 73104, United States
UT Southwestern Simmons Cancer Center - RedBird
Dallas Texas, 75237, United States
UT Southwestern/Simmons Cancer Center-Dallas
Dallas Texas, 75390, United States
UT Southwestern/Simmons Cancer Center-Fort Worth
Fort Worth Texas, 76104, United States
UT Southwestern Clinical Center at Richardson/Plano
Richardson Texas, 75080, United States
Marshfield Medical Center-Marshfield
Marshfield Wisconsin, 54449, United States
Marshfield Clinic-Minocqua Center
Minocqua Wisconsin, 54548, United States
Marshfield Medical Center-River Region at Stevens Point
Stevens Point Wisconsin, 54482, United States
Marshfield Medical Center - Weston
Weston Wisconsin, 54476, United States

How clear is this clinincal trial information?

Study is for people with:

Bladder Cancer

Phase:

Phase 2

Estimated Enrollment:

196

Study ID:

NCT04871529

Recruitment Status:

Suspended

Sponsor:


SWOG Cancer Research Network

How clear is this clinincal trial information?

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