AzTrials
AzTrials

Bladder Carcinoma Infiltrating the Muscle of the Bladder WallPhase 2NCT04871529

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)

A Phase 2 study testing Therapeutic Conventional Surgery, Avelumab and Gemcitabine Hydrochloride in people with Bladder Carcinoma Infiltrating the Muscle of the Bladder Wall and Infiltrating Renal Pelvis and Ureter Urothelial Carcinoma, run by SWOG Cancer Research Network at 92 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Therapeutic Conventional Surgery, Avelumab and Gemcitabine Hydrochloride
Could I receive a placebo?
No, everyone receives an active treatment
How many people
6 participants
Where
92 sitesUnited States
Study dates
10 Aug 2022to 26 Jun 2024
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 28Show fewer
  • 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

Who cannot join

  • 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

Trial locations and contacts

92 sites in 1 country.

92 sites in 1 country

United States92 sites

  • Pali Momi Medical Center

    ‘Aiea, Hawaii, 96701

  • Saint Anthony's Health

    Alton, Illinois, 62002

  • Mary Greeley Medical Center

    Ames, Iowa, 50010

  • McFarland Clinic - Ames

    Ames, Iowa, 50010

  • Saint Joseph Mercy Hospital

    Ann Arbor, Michigan, 48106

  • University of Colorado Hospital

    Aurora, Colorado, 80045

  • Illinois CancerCare-Bloomington

    Bloomington, Illinois, 61704

  • McFarland Clinic - Boone

    Boone, Iowa, 50036

  • Saint Joseph Mercy Brighton

    Brighton, Michigan, 48114

  • Trinity Health IHA Medical Group Hematology Oncology - Brighton

    Brighton, Michigan, 48114

  • Illinois CancerCare-Canton

    Canton, Illinois, 61520

  • Saint Joseph Mercy Canton

    Canton, Michigan, 48188

  • Trinity Health IHA Medical Group Hematology Oncology - Canton

    Canton, Michigan, 48188

  • Saint Francis Medical Center

    Cape Girardeau, Missouri, 63703

  • Illinois CancerCare-Carthage

    Carthage, Illinois, 62321

  • Saint Joseph Mercy Chelsea

    Chelsea, Michigan, 48118

  • Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital

    Chelsea, Michigan, 48118

  • Northwestern University

    Chicago, Illinois, 60611

  • University of Illinois

    Chicago, Illinois, 60612

  • Hematology Oncology Consultants-Clarkston

    Clarkston, Michigan, 48346

  • Newland Medical Associates-Clarkston

    Clarkston, Michigan, 48346

  • Cleveland Clinic Cancer Center/Fairview Hospital

    Cleveland, Ohio, 44111

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • Mercy Hospital

    Coon Rapids, Minnesota, 55433

  • UT Southwestern Simmons Cancer Center - RedBird

    Dallas, Texas, 75237

  • UT Southwestern/Simmons Cancer Center-Dallas

    Dallas, Texas, 75390

  • Carle at The Riverfront

    Danville, Illinois, 61832

  • Cancer Care Specialists of Illinois - Decatur

    Decatur, Illinois, 62526

  • Decatur Memorial Hospital

    Decatur, Illinois, 62526

  • Northwestern Medicine Cancer Center Kishwaukee

    DeKalb, Illinois, 60115

  • Illinois CancerCare-Dixon

    Dixon, Illinois, 61021

  • Carle Physician Group-Effingham

    Effingham, Illinois, 62401

  • Crossroads Cancer Center

    Effingham, Illinois, 62401

  • Illinois CancerCare-Eureka

    Eureka, Illinois, 61530

  • NorthShore University HealthSystem-Evanston Hospital

    Evanston, Illinois, 60201

  • Parkland Health Center - Farmington

    Farmington, Missouri, 63640

  • Genesee Cancer and Blood Disease Treatment Center

    Flint, Michigan, 48503

  • Genesee Hematology Oncology PC

    Flint, Michigan, 48503

  • Genesys Hurley Cancer Institute

    Flint, Michigan, 48503

  • McFarland Clinic - Trinity Cancer Center

    Fort Dodge, Iowa, 50501

  • UT Southwestern/Simmons Cancer Center-Fort Worth

    Fort Worth, Texas, 76104

  • Illinois CancerCare-Galesburg

    Galesburg, Illinois, 61401

  • Northwestern Medicine Cancer Center Delnor

    Geneva, Illinois, 60134

  • NorthShore University HealthSystem-Glenbrook Hospital

    Glenview, Illinois, 60026

  • NorthShore University HealthSystem-Highland Park Hospital

    Highland Park, Illinois, 60035

  • UCHealth Highlands Ranch Hospital

    Highlands Ranch, Colorado, 80129

  • Queen's Medical Center

    Honolulu, Hawaii, 96813

  • Straub Clinic and Hospital

    Honolulu, Hawaii, 96813

  • McFarland Clinic - Jefferson

    Jefferson, Iowa, 50129

  • Illinois CancerCare-Kewanee Clinic

    Kewanee, Illinois, 61443

  • Northwestern Medicine Lake Forest Hospital

    Lake Forest, Illinois, 60045

  • Trinity Health Saint Mary Mercy Livonia Hospital

    Livonia, Michigan, 48154

  • Illinois CancerCare-Macomb

    Macomb, Illinois, 61455

  • Cleveland Clinic Cancer Center Mansfield

    Mansfield, Ohio, 44906

  • McFarland Clinic - Marshalltown

    Marshalltown, Iowa, 50158

  • Marshfield Medical Center-Marshfield

    Marshfield, Wisconsin, 54449

  • Carle Physician Group-Mattoon/Charleston

    Mattoon, Illinois, 61938

  • Hillcrest Hospital Cancer Center

    Mayfield Heights, Ohio, 44124

  • East Jefferson General Hospital

    Metairie, Louisiana, 70006

  • LSU Healthcare Network / Metairie Multi-Specialty Clinic

    Metairie, Louisiana, 70006

  • Marshfield Clinic-Minocqua Center

    Minocqua, Wisconsin, 54548

  • Cancer Care Center of O'Fallon

    O'Fallon, Illinois, 62269

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • AdventHealth Orlando

    Orlando, Florida, 32803

  • Illinois CancerCare-Ottawa Clinic

    Ottawa, Illinois, 61350

  • Illinois CancerCare-Pekin

    Pekin, Illinois, 61554

  • Illinois CancerCare-Peoria

    Peoria, Illinois, 61615

  • Illinois CancerCare-Peru

    Peru, Illinois, 61354

  • Newland Medical Associates-Pontiac

    Pontiac, Michigan, 48341

  • Saint Joseph Mercy Oakland

    Pontiac, Michigan, 48341

  • Illinois CancerCare-Princeton

    Princeton, Illinois, 61356

  • UT Southwestern Clinical Center at Richardson/Plano

    Richardson, Texas, 75080

  • Ascension Saint Mary's Hospital

    Saginaw, Michigan, 48601

  • Oncology Hematology Associates of Saginaw Valley PC

    Saginaw, Michigan, 48604

  • Sainte Genevieve County Memorial Hospital

    Sainte Genevieve, Missouri, 63670

  • North Coast Cancer Care

    Sandusky, Ohio, 44870

  • Southern Illinois University School of Medicine

    Springfield, Illinois, 62702

  • Springfield Clinic

    Springfield, Illinois, 62702

  • Memorial Medical Center

    Springfield, Illinois, 62781

  • Missouri Baptist Medical Center

    St Louis, Missouri, 63131

  • Marshfield Medical Center-River Region at Stevens Point

    Stevens Point, Wisconsin, 54482

  • Missouri Baptist Sullivan Hospital

    Sullivan, Missouri, 63080

  • Missouri Baptist Outpatient Center-Sunset Hills

    Sunset Hills, Missouri, 63127

  • ProMedica Flower Hospital

    Sylvania, Ohio, 43560

  • Ascension Saint Joseph Hospital

    Tawas City, Michigan, 48764

  • Carle Cancer Center

    Urbana, Illinois, 61801

  • Northwestern Medicine Cancer Center Warrenville

    Warrenville, Illinois, 60555

  • Illinois CancerCare - Washington

    Washington, Illinois, 61571

  • Marshfield Medical Center - Weston

    Weston, Wisconsin, 54476

  • Cleveland Clinic Wooster Family Health and Surgery Center

    Wooster, Ohio, 44691

  • Huron Gastroenterology PC

    Ypsilanti, Michigan, 48106

  • Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus

    Ypsilanti, Michigan, 48197

Other trials in United States

About this study

Official title: Randomized Phase II Trial of Gemcitabine, Avelumab and Carboplatin vs. No Neoadjuvant Therapy Preceding Surgery for Cisplatin-Ineligible Muscle-Invasive Urothelial Carcinoma: SWOG GAP TRIAL

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. 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:

  1. 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:

  1. 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.

Medical subject headings
Urinary Bladder Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Therapeutic Conventional SurgeryProcedure or surgery

    Undergo surgery

  • AvelumabDrug

    Also called 1537032-82-8, Bavencio, Immunoglobulin G1-lambda1, Anti-(Homo sapiens CD274 (Programmed Death Ligand 1, PDL1, pd-l1, B7 Homolog 1, B7H1))

    Given IV

  • Gemcitabine HydrochlorideDrug

    Also called 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

    Given IV

  • CarboplatinDrug

    Also called (SP-4-2)-diammine[1,1-cyclobutanedicarboxylato(2--)-O,O'']platinum, 1,1-cyclobutanedicarboxylic acid platinum complex, 41575-94-4, Blastocarb

    Given IV

Study groups in NCT04871529
Study groupRoleWhat they receive
Arm A (avelumab, gemcitabine, carboplatin, surgery)ExperimentalPatients 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.
Receives: Procedure: Therapeutic Conventional Surgery; Drug: Avelumab; Drug: Gemcitabine Hydrochloride; Drug: Carboplatin
Arm B (surgery)ExperimentalPatients undergo standard of care surgery.
Receives: Procedure: Therapeutic Conventional Surgery

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Pathologic Complete Response

    Compare pathologic complete response (pCR) between arms. pCR is defined as s absence of all disease in the surgical specimen from radical cystectomy, nephroureterectomy or ureterectomy as determined by the pathologist at the institution. This is determined by a biopsy taken at the time of surgery.

    Measured: Measured once - at the time of surgery

Secondary outcomes (4)

  1. Event-free Survival

    Compare event-free survival between arms. Event-free survival is defined as the time from randomization to the first EFS event. For those who do not undergo surgery, event time will be assigned to the date of disease assessment that indicated surgery was no longer indicated or physician decision not to conduct the surgery.

    Measured: From randomization to the first event, assessed up to study closure

  2. Incidence of Adverse Events

    Evaluate toxicities on both arms. Number of participants with Grade 3-5 adverse events that are possibly, probably or definitely related to study drug are reported. Measured using CTCAE v5.0.

    Measured: treatment start to 90 days post surgery

  3. Overall Survival

    To compare overall survival between arms. Overall survival is defined as time from date of registration to date of death due to any cause or patients last known to be alive are censored at their last contact date.

    Measured: Up to 5 years post-surgery

  4. Pathologic Complete Response - After 2 Cycles

    Compare pathologic complete response (pCR) between surgery only arm and participants in the avelumab, gemcitabine, carboplatin, surgery arm who received at least two cycles of treatment. pCR is defined as s absence of all disease in the surgical specimen from radical cystectomy, nephroureterectomy or ureterectomy as determined by the pathologist at the institution. This is determined using a biopsy taken at the time of surgery.

    This outcome uses a subset of participants in arm A who completed exactly 2 cycles of neoadjuvant treatment.

    Measured: Measured once - at the time of surgery

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 May 2021
  2. Study start10 Aug 2022
  3. Primary completion14 Nov 2023
  4. Study completion26 Jun 2024

Why it stopped: inability to accrue sufficient patients

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
6 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04871529
Sponsor's protocol ID
S2011
Other IDs
NCI-2021-02265
Status last verified
Dec 2024
First submitted
29 Apr 2021
Last updated
30 Dec 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Therapeutic Conventional Surgery, Avelumab and Gemcitabine Hydrochloride in people with Bladder Carcinoma Infiltrating the Muscle of the Bladder Wall and Infiltrating Renal Pelvis and Ureter Urothelial Carcinoma, run by SWOG Cancer Research Network at 92 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 28 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 30 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 92 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 Dec 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pathologic Complete Response (time frame: Measured once - at the time of surgery). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04871529.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Dec 2024.

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