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Brief Title: 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)

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

INTRODUCTION

  • Org Study ID: S2011
  • Secondary ID: NCI-2021-02265, S1905, S1905, U10CA180888
  • NTC ID: NCT04871529
  • Sponsor: Southwest Oncology Group

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.

  • Overall Status
    Recruiting
  • Start Date
    October 6, 2021
  • Phase
    Phase 2
  • Study Type
    Interventional

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: pathologic complete response

Primary Outcome 1 - Timeframe: up to 5 years post-surgery

CONDITION

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

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

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: N/A

Role: N/A

Affiliation: N/A

Overall Contact

Name: N/A

Phone: 617/632-2429, 210/567-1100

Email: gurup_sonpavde@dfci.harvard.edu, liss@uthscsa.edu

LOCATION

Facility Status Contact
Facility: Illinois CancerCare-Bloomington
Bloomington, Illinois 61704
United States
Status: Recruiting Contact: Contact
Site Public Contact
309-243-3605
andersonj@illinoiscancercare.com
Facility: Illinois CancerCare-Canton
Canton, Illinois 61520
United States
Status: Recruiting Contact: Principal Investigator
Bryan A. Faller
309-243-3605
andersonj@illinoiscancercare.com
Facility: Illinois CancerCare-Carthage
Carthage, Illinois 62321
United States
Status: Recruiting Contact: Contact
Site Public Contact
309-243-3605
andersonj@illinoiscancercare.com
Facility: Cancer Care Specialists of Illinois - Decatur
Decatur, Illinois 62526
United States
Status: Recruiting Contact: Principal Investigator
Bryan A. Faller
217-876-4762
morganthaler.jodi@mhsil.com
Facility: Illinois CancerCare-Dixon
Dixon, Illinois 61021
United States
Status: Recruiting Contact: Contact
Site Public Contact
815-285-7800
morganthaler.jodi@mhsil.com
Facility: Crossroads Cancer Center
Effingham, Illinois 62401
United States
Status: Recruiting Contact: Principal Investigator
Bryan A. Faller
217-876-4762
andersonj@illinoiscancercare.com
Facility: Illinois CancerCare-Eureka
Eureka, Illinois 61530
United States
Status: Recruiting Contact: Contact
Site Public Contact
309-243-3605
andersonj@illinoiscancercare.com
Facility: Illinois CancerCare-Galesburg
Galesburg, Illinois 61401
United States
Status: Recruiting Contact: Principal Investigator
Bryan A. Faller
309-243-3605
andersonj@illinoiscancercare.com
Facility: Illinois CancerCare-Kewanee Clinic
Kewanee, Illinois 61443
United States
Status: Recruiting Contact: Contact
Site Public Contact
309-243-3605
andersonj@illinoiscancercare.com
Facility: Illinois CancerCare-Macomb
Macomb, Illinois 61455
United States
Status: Recruiting Contact: Principal Investigator
Bryan A. Faller
309-243-3605
andersonj@illinoiscancercare.com
Facility: Illinois CancerCare-Ottawa Clinic
Ottawa, Illinois 61350
United States
Status: Recruiting Contact: Contact
Site Public Contact
309-243-3605
andersonj@illinoiscancercare.com
Facility: Illinois CancerCare-Pekin
Pekin, Illinois 61554
United States
Status: Recruiting Contact: Principal Investigator
Bryan A. Faller
309-243-3605
andersonj@illinoiscancercare.com
Facility: Illinois CancerCare-Peoria
Peoria, Illinois 61615
United States
Status: Recruiting Contact: Contact
Site Public Contact
309-243-3605
andersonj@illinoiscancercare.com
Facility: Illinois CancerCare-Peru
Peru, Illinois 61354
United States
Status: Recruiting Contact: Principal Investigator
Bryan A. Faller
309-243-3605
andersonj@illinoiscancercare.com
Facility: Illinois CancerCare-Princeton
Princeton, Illinois 61356
United States
Status: Recruiting Contact: Contact
Site Public Contact
309-243-3605
andersonj@illinoiscancercare.com
Facility: Southern Illinois University School of Medicine
Springfield, Illinois 62702
United States
Status: Recruiting Contact: Principal Investigator
Bryan A. Faller
217-545-7929
ksoder@mcfarlandclinic.com
Facility: Illinois CancerCare - Washington
Washington, Illinois 61571
United States
Status: Recruiting Contact: Contact
Site Public Contact
309-243-3605
Facility: Mary Greeley Medical Center
Ames, Iowa 50010
United States
Status: Recruiting Contact: Principal Investigator
Bryan A. Faller
515-956-4132
Facility: McFarland Clinic PC - Ames
Ames, Iowa 50010
United States
Status: Recruiting Contact: Contact
Site Public Contact
515-239-4734
Facility: McFarland Clinic PC-Boone
Boone, Iowa 50036
United States
Status: Recruiting Contact: Principal Investigator
Bryan A. Faller
515-956-4132
Facility: McFarland Clinic PC-Trinity Cancer Center
Fort Dodge, Iowa 50501
United States
Status: Recruiting Contact: Contact
Site Public Contact
515-956-4132
Facility: McFarland Clinic PC-Jefferson
Jefferson, Iowa 50129
United States
Status: Recruiting Contact: Principal Investigator
Bryan A. Faller
515-956-4132
Facility: McFarland Clinic PC-Marshalltown
Marshalltown, Iowa 50158
United States
Status: Recruiting Contact: Contact
Site Public Contact
515-956-4132