Overview

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 (SW

Status:
Recruiting
Trial end date:
2029-04-30
Target enrollment:
0
Participant gender:
All
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.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Southwest Oncology Group
Collaborator:
National Cancer Institute (NCI)
Treatments:
Antibodies, Monoclonal
Avelumab
Carboplatin
Gemcitabine
Immunoglobulin G
Immunoglobulins
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