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)

NCT ID: NCT04871529

Last Updated: 2024-12-30

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-08-10
• Study Completion Date: 2024-06-26

Brief 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.

Detailed 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.

Conditions

Bladder Carcinoma Infiltrating the Muscle of the Bladder Wall; Infiltrating Renal Pelvis and Ureter Urothelial Carcinoma; Stage II Bladder Cancer AJCC v8

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A (avelumab, gemcitabine, carboplatin, surgery)

Patients receive avelumab 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.

Group Type: EXPERIMENTAL

Therapeutic Conventional Surgery

Intervention Type: PROCEDURE

Undergo surgery

Avelumab

Intervention Type: DRUG

Given IV

Gemcitabine Hydrochloride

Intervention Type: DRUG

Given IV

Carboplatin

Intervention Type: DRUG

Given IV

Arm B (surgery)

Patients undergo standard of care surgery.

Group Type: EXPERIMENTAL

Therapeutic Conventional Surgery

Intervention Type: PROCEDURE

Undergo surgery

Interventions

Therapeutic Conventional Surgery

Undergo surgery

Intervention Type: PROCEDURE

Avelumab

Given IV

Intervention Type: DRUG

Gemcitabine Hydrochloride

Given IV

Intervention Type: DRUG

Carboplatin

Given IV

Intervention Type: DRUG

Other Intervention Names

1537032-82-8; Bavencio; Immunoglobulin G1-lambda1; Anti-(Homo sapiens CD274 (Programmed Death Ligand 1, PDL1, pd-l1, B7 Homolog 1, B7H1)); Homo sapiens Monoclonal Antibody; MSB-0010718C; MSB0010718C; 1-(2-Oxo-4-amino-1,2-dihydropyrimidin-1-yl)-2-deoxy-2,2-difluororibose, hydrochloride; 122111-03-9; 2''Deoxy-2'',2''-Difluorocytidine Hydrochloride; dFdCyd; Difluorodeoxycytidine Hydrochloride; FF 10832; FF-10832; FF10832; Gemcitabine HCI; Gemzar; LY-188011; LY188011; (SP-4-2)-diammine[1,1-cyclobutanedicarboxylato(2--)-O,O'']platinum; 1,1-cyclobutanedicarboxylic acid platinum complex; 41575-94-4; Blastocarb; Carboplat; Carboplatin Hexal; Carboplatino; Carboplatinum; Carbosin; Carbosol; Carbotec; CBDCA; cis-diammine(1,1-cyclobutanedicarboxylato) platinum(II); Cis-Diammine(cyclobutane-1,1-dicarboxylato)platinum; cis-diammine(cyclobutanedicarboxylato)platinum II; Displata; Ercar; JM-8; Nealorin; Novoplatinum; Paraplatin; Paraplatin AQ; Paraplatine; platinum; diammine(1,1-cyclobutanedicarboxylato(2-))-, (SP-4-2)

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

SWOG Cancer Research Network

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University of Colorado Hospital

Aurora, Colorado, United States

UCHealth Highlands Ranch Hospital

Highlands Ranch, Colorado, United States

AdventHealth Orlando

Orlando, Florida, United States

Queen's Medical Center

Honolulu, Hawaii, United States

Straub Clinic and Hospital

Honolulu, Hawaii, United States

Pali Momi Medical Center

‘Aiea, Hawaii, United States

Saint Anthony's Health

Alton, Illinois, United States

Illinois CancerCare-Bloomington

Bloomington, Illinois, United States

Illinois CancerCare-Canton

Canton, Illinois, United States

Illinois CancerCare-Carthage

Carthage, Illinois, United States

Northwestern University

Chicago, Illinois, United States

University of Illinois

Chicago, Illinois, 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

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

Illinois CancerCare-Kewanee Clinic

Kewanee, Illinois, United States

Northwestern Medicine Lake Forest Hospital

Lake Forest, Illinois, United States

Illinois CancerCare-Macomb

Macomb, Illinois, United States

Carle Physician Group-Mattoon/Charleston

Mattoon, Illinois, United States

Cancer Care Center of O'Fallon

O'Fallon, Illinois, 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

Illinois CancerCare-Princeton

Princeton, Illinois, United States

Southern Illinois University School of Medicine

Springfield, Illinois, United States

Springfield Clinic

Springfield, Illinois, United States

Memorial Medical Center

Springfield, Illinois, 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

Mary Greeley Medical Center

Ames, Iowa, United States

McFarland Clinic - Ames

Ames, Iowa, United States

McFarland Clinic - Boone

Boone, Iowa, United States

McFarland Clinic - Trinity Cancer Center

Fort Dodge, Iowa, United States

McFarland Clinic - Jefferson

Jefferson, Iowa, United States

McFarland Clinic - Marshalltown

Marshalltown, Iowa, United States

East Jefferson General Hospital

Metairie, Louisiana, United States

LSU Healthcare Network / Metairie Multi-Specialty Clinic

Metairie, Louisiana, United States

Saint Joseph Mercy Hospital

Ann Arbor, Michigan, United States

Saint Joseph Mercy Brighton

Brighton, Michigan, United States

Trinity Health IHA Medical Group Hematology Oncology - Brighton

Brighton, Michigan, United States

Saint Joseph Mercy Canton

Canton, Michigan, United States

Trinity Health IHA Medical Group Hematology Oncology - Canton

Canton, Michigan, United States

Saint Joseph Mercy Chelsea

Chelsea, Michigan, United States

Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital

Chelsea, Michigan, United States

Hematology Oncology Consultants-Clarkston

Clarkston, Michigan, United States

Newland Medical Associates-Clarkston

Clarkston, Michigan, 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

Trinity Health Saint Mary Mercy Livonia Hospital

Livonia, Michigan, United States

Newland Medical Associates-Pontiac

Pontiac, Michigan, United States

Saint Joseph Mercy Oakland

Pontiac, Michigan, United States

Ascension Saint Mary's Hospital

Saginaw, Michigan, United States

Oncology Hematology Associates of Saginaw Valley PC

Saginaw, Michigan, United States

Ascension Saint Joseph Hospital

Tawas City, Michigan, United States

Huron Gastroenterology PC

Ypsilanti, Michigan, United States

Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus

Ypsilanti, Michigan, United States

Mercy Hospital

Coon Rapids, Minnesota, United States

Saint Francis Medical Center

Cape Girardeau, Missouri, United States

Parkland Health Center - Farmington

Farmington, Missouri, United States

Sainte Genevieve County Memorial Hospital

Sainte Genevieve, Missouri, United States

Missouri Baptist Medical Center

St Louis, Missouri, United States

Missouri Baptist Sullivan Hospital

Sullivan, Missouri, United States

Missouri Baptist Outpatient Center-Sunset Hills

Sunset Hills, Missouri, United States

Cleveland Clinic Cancer Center/Fairview Hospital

Cleveland, Ohio, United States

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Cleveland Clinic Cancer Center Mansfield

Mansfield, Ohio, United States

Hillcrest Hospital Cancer Center

Mayfield Heights, Ohio, United States

North Coast Cancer Care

Sandusky, Ohio, United States

ProMedica Flower Hospital

Sylvania, Ohio, United States

Cleveland Clinic Wooster Family Health and Surgery Center

Wooster, Ohio, United States

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

UT Southwestern Simmons Cancer Center - RedBird

Dallas, Texas, United States

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, United States

UT Southwestern/Simmons Cancer Center-Fort Worth

Fort Worth, Texas, United States

UT Southwestern Clinical Center at Richardson/Plano

Richardson, Texas, United States

Marshfield Medical Center-Marshfield

Marshfield, Wisconsin, United States

Marshfield Clinic-Minocqua Center

Minocqua, Wisconsin, United States

Marshfield Medical Center-River Region at Stevens Point

Stevens Point, Wisconsin, United States

Marshfield Medical Center - Weston

Weston, Wisconsin, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

NCI-2021-02265

Identifier Type: REGISTRY

Identifier Source: secondary_id

S2011

Identifier Type: -

Identifier Source: org_study_id