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Clinical Trial Details — Status: Suspended

Administrative data

NCT number NCT04871529
Other study ID # S2011
Secondary ID NCI-2021-02265S1
Status Suspended
Phase Phase 2
First received
Last updated
Start date August 10, 2022
Est. completion date April 30, 2029

Study information

Verified date August 2023
Source SWOG Cancer Research Network
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical 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.


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.


Recruitment information / eligibility

Status Suspended
Enrollment 196
Est. completion date April 30, 2029
Est. primary completion date April 30, 2027
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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 Design


Related Conditions & MeSH terms


Intervention

Procedure:
Therapeutic Conventional Surgery
Undergo surgery
Drug:
Avelumab
Given IV
Gemcitabine Hydrochloride
Given IV
Carboplatin
Given IV

Locations

Country Name City State
United States Pali Momi Medical Center 'Aiea Hawaii
United States Saint Anthony's Health Alton Illinois
United States Mary Greeley Medical Center Ames Iowa
United States McFarland Clinic - Ames Ames Iowa
United States Saint Joseph Mercy Hospital Ann Arbor Michigan
United States University of Colorado Hospital Aurora Colorado
United States Illinois CancerCare-Bloomington Bloomington Illinois
United States McFarland Clinic - Boone Boone Iowa
United States Saint Joseph Mercy Brighton Brighton Michigan
United States Trinity Health IHA Medical Group Hematology Oncology - Brighton Brighton Michigan
United States Illinois CancerCare-Canton Canton Illinois
United States Saint Joseph Mercy Canton Canton Michigan
United States Trinity Health IHA Medical Group Hematology Oncology - Canton Canton Michigan
United States Saint Francis Medical Center Cape Girardeau Missouri
United States Illinois CancerCare-Carthage Carthage Illinois
United States Saint Joseph Mercy Chelsea Chelsea Michigan
United States Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital Chelsea Michigan
United States Northwestern University Chicago Illinois
United States University of Illinois Chicago Illinois
United States Hematology Oncology Consultants-Clarkston Clarkston Michigan
United States Newland Medical Associates-Clarkston Clarkston Michigan
United States Cleveland Clinic Cancer Center/Fairview Hospital Cleveland Ohio
United States Cleveland Clinic Foundation Cleveland Ohio
United States Mercy Hospital Coon Rapids Minnesota
United States UT Southwestern Simmons Cancer Center - RedBird Dallas Texas
United States UT Southwestern/Simmons Cancer Center-Dallas Dallas Texas
United States Carle at The Riverfront Danville Illinois
United States Cancer Care Specialists of Illinois - Decatur Decatur Illinois
United States Decatur Memorial Hospital Decatur Illinois
United States Northwestern Medicine Cancer Center Kishwaukee DeKalb Illinois
United States Illinois CancerCare-Dixon Dixon Illinois
United States Carle Physician Group-Effingham Effingham Illinois
United States Crossroads Cancer Center Effingham Illinois
United States Illinois CancerCare-Eureka Eureka Illinois
United States NorthShore University HealthSystem-Evanston Hospital Evanston Illinois
United States Parkland Health Center - Farmington Farmington Missouri
United States Genesee Cancer and Blood Disease Treatment Center Flint Michigan
United States Genesee Hematology Oncology PC Flint Michigan
United States Genesys Hurley Cancer Institute Flint Michigan
United States McFarland Clinic - Trinity Cancer Center Fort Dodge Iowa
United States UT Southwestern/Simmons Cancer Center-Fort Worth Fort Worth Texas
United States Illinois CancerCare-Galesburg Galesburg Illinois
United States Northwestern Medicine Cancer Center Delnor Geneva Illinois
United States NorthShore University HealthSystem-Glenbrook Hospital Glenview Illinois
United States NorthShore University HealthSystem-Highland Park Hospital Highland Park Illinois
United States UCHealth Highlands Ranch Hospital Highlands Ranch Colorado
United States Queen's Medical Center Honolulu Hawaii
United States Straub Clinic and Hospital Honolulu Hawaii
United States McFarland Clinic - Jefferson Jefferson Iowa
United States Illinois CancerCare-Kewanee Clinic Kewanee Illinois
United States Northwestern Medicine Lake Forest Hospital Lake Forest Illinois
United States Trinity Health Saint Mary Mercy Livonia Hospital Livonia Michigan
United States Illinois CancerCare-Macomb Macomb Illinois
United States Cleveland Clinic Cancer Center Mansfield Mansfield Ohio
United States McFarland Clinic - Marshalltown Marshalltown Iowa
United States Marshfield Medical Center-Marshfield Marshfield Wisconsin
United States Carle Physician Group-Mattoon/Charleston Mattoon Illinois
United States Hillcrest Hospital Cancer Center Mayfield Heights Ohio
United States East Jefferson General Hospital Metairie Louisiana
United States LSU Healthcare Network / Metairie Multi-Specialty Clinic Metairie Louisiana
United States Marshfield Clinic-Minocqua Center Minocqua Wisconsin
United States Cancer Care Center of O'Fallon O'Fallon Illinois
United States University of Oklahoma Health Sciences Center Oklahoma City Oklahoma
United States AdventHealth Orlando Orlando Florida
United States Illinois CancerCare-Ottawa Clinic Ottawa Illinois
United States Illinois CancerCare-Pekin Pekin Illinois
United States Illinois CancerCare-Peoria Peoria Illinois
United States Illinois CancerCare-Peru Peru Illinois
United States Newland Medical Associates-Pontiac Pontiac Michigan
United States Saint Joseph Mercy Oakland Pontiac Michigan
United States Illinois CancerCare-Princeton Princeton Illinois
United States UT Southwestern Clinical Center at Richardson/Plano Richardson Texas
United States Ascension Saint Mary's Hospital Saginaw Michigan
United States Oncology Hematology Associates of Saginaw Valley PC Saginaw Michigan
United States Missouri Baptist Medical Center Saint Louis Missouri
United States Sainte Genevieve County Memorial Hospital Sainte Genevieve Missouri
United States North Coast Cancer Care Sandusky Ohio
United States Memorial Medical Center Springfield Illinois
United States Southern Illinois University School of Medicine Springfield Illinois
United States Springfield Clinic Springfield Illinois
United States Marshfield Medical Center-River Region at Stevens Point Stevens Point Wisconsin
United States Missouri Baptist Sullivan Hospital Sullivan Missouri
United States Missouri Baptist Outpatient Center-Sunset Hills Sunset Hills Missouri
United States ProMedica Flower Hospital Sylvania Ohio
United States Ascension Saint Joseph Hospital Tawas City Michigan
United States Carle Cancer Center Urbana Illinois
United States Northwestern Medicine Cancer Center Warrenville Warrenville Illinois
United States Illinois CancerCare - Washington Washington Illinois
United States Marshfield Medical Center - Weston Weston Wisconsin
United States Cleveland Clinic Wooster Family Health and Surgery Center Wooster Ohio
United States Huron Gastroenterology PC Ypsilanti Michigan
United States Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus Ypsilanti Michigan

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 pathologic complete response up to 5 years post-surgery
Secondary Event-free survival From randomization to the first event, assessed up to 5 years post surgery
Secondary Incidence of adverse events Will utilize the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 for toxicity and serious adverse event reporting Up to 90 days post-surgery
Secondary Overall survival Up to 5 years post-surgery
See also
  Status Clinical Trial Phase
Completed NCT03617913 - Avelumab in Combination With Fluorouracil and Mitomycin or Cisplatin and Radiation Therapy in Treating Participants With Muscle-Invasive Bladder Cancer Phase 2
Withdrawn NCT05564416 - Testing Anti-Cancer Drugs Erdafitinib With or Without Atezolizumab in Patients With Localized Bladder Cancer Not Able to Receive Cisplatin Chemotherapy, NERA Trial Phase 2
Recruiting NCT06350734 - Quality of Life After Treatment for Bladder Cancer: The Bladder Cancer Survivorship Study
Recruiting NCT04383743 - Pembrolizumab and Combination Chemotherapy Before Surgery for the Treatment of Muscle-Invasive Bladder Cancer Phase 2
Active, not recruiting NCT03775265 - Chemoradiotherapy With or Without Atezolizumab in Treating Patients With Localized Muscle Invasive Bladder Cancer Phase 3
Recruiting NCT05581589 - Sacituzumab Govitecan Before Radical Cystectomy for the Treatment of Non-Urothelial Muscle Invasive Bladder Cancer Phase 2
Completed NCT00749892 - Erlotinib Hydrochloride in Treating Participants With Muscle Invasive or Recurrent Urothelial Cancer Phase 2
Not yet recruiting NCT06263153 - Futibatinib in Combination With Durvalumab Prior to Cystectomy for the Treatment of Muscle-Invasive Bladder Cancer Patients Who Are Ineligible for Cisplatin-based Therapy Phase 2
Completed NCT03319745 - Pembrolizumab in Treating Patients With Bladder Cancer Undergoing Radical Cystectomy Phase 2
Active, not recruiting NCT04501913 - Remote Telemonitoring of Patient-Generated Physiologic Health Data and Patient-Reported Outcomes
Recruiting NCT06040762 - A Home-Based Prehabilitation Exercise Intervention for Improving Physical Function in Patients Receiving Chemotherapy Before Radical Cystectomy, Get Moving Trial N/A