Duration of Immune Checkpoint Therapy in Locally Advanced or Metastatic Urothelial Carcinoma: A Randomized Phase 3 Non-Inferiority Trial (A031901)

NOT ENROLLING
Protocol # :
21-392
Conditions
Locally Advanced Bladder Urothelial Carcinoma
Locally Advanced Renal Pelvis Urothelial Carcinoma
Locally Advanced Ureter Urothelial Carcinoma
Locally Advanced Urethral Urothelial Carcinoma
Locally Advanced Urothelial Carcinoma
Metastatic Bladder Urothelial Carcinoma
Metastatic Renal Pelvis Urothelial Carcinoma
Metastatic Ureter Urothelial Carcinoma
Metastatic Urethral Urothelial Carcinoma
Metastatic Urothelial Carcinoma
Phase
III
Disease Sites
Urinary Bladder
Other Urinary
Principal Investigator
Wei, Xiao, Xiao
Site Research Nurses
Brule, Maurice, N.
Fleming, Norah, Michelle
Freeman, Stefani, Danielle
Gentile, Alissa
Hixon, Nicole, R.
Kosinski, Michelle
Piper, Audrey, L.

Trial Description

This phase III trial compares survival in urothelial cancer patients who stop immune
checkpoint inhibitor treatment after being treated for about a year to those patients who
continue treatment with immune checkpoint inhibitors. Immunotherapy with monoclonal
antibodies, such as avelumab, durvalumab, pembrolizumab, atezolizumab, and nivolumab, may
help the body's immune system attack the cancer, and may interfere with the ability of tumor
cells to grow and spread. Stopping immune checkpoint inhibitors early may still make the
tumor shrink and patients may have similar survival rates as the patients who continue
treatment. Stopping treatment early may also lead to fewer treatment-related side effects, an
improvement in mental health, and a lower cost burden to patients.

Eligibility Requirements

- Documentation of disease

- Histologic documentation: Histologically or cytologically confirmed urothelial
carcinoma (UC) with predominantly transitional-cell features

- Stage: Locally advanced or metastatic disease prior to starting immune checkpoint
blockade

- Tumor Site: Bladder, renal pelvis, ureter, urethra, or prostate

- Patients must have received at least one cycle of current active treatment with
standard of care (SOC) Food and Drug Administration (FDA) approved PD-1/L1 immune
checkpoint inhibitor (ICI)-containing therapy for locally advance or metastatic UC

- Patients without progressive disease per Response Evaluation Criteria in Solid Tumors
(RECIST) version (v) 1.1 guidelines (i.e., with an ongoing [complete response] CR,
partial response [PR], or stable disease [SD]) following completion of 12-15 months of
ICI treatment

- No history of tuberculosis, active hepatitis B (HBV) or hepatitis C (HCV), or
uncontrolled human immunodeficiency virus (HIV)

- Patients with resolved HBV infection, defined as positive hepatitis B core
antibody (anti-Hb) and negative hepatitis B surface antigen (HbsAg), are eligible

- Patients with positive HCV antibody are eligible if HCV ribonucleic acid (RNA)
polymerase chain reaction (PCR) is negative

- Patients with HIV who are compliant with highly active antiretroviral therapy
(HAART) and have normal CD4 count and undetectable viral load are eligible

- No history of allogeneic organ transplantation

- No current immunosuppressive medication exceeding 10 mg/day of prednisone or its
equivalent

* Patients with pre-existing or treatment-emergent autoimmune or inflammatory
disorders which do not require systemic immunosuppressive treatment exceeding 10
mg/day of prednisone or its equivalent may be included

- No history of another primary malignancy except for malignancy treated with curative
intent with no known active disease for >= 2 years, and adequately treated
non-melanomatous skin cancer or carcinoma in situ (e.g. cervical carcinoma in situ
[CIS]) without evidence of disease

- No female patients who are pregnant or breastfeeding, or male or female patients of
reproductive potential who are not willing to employ effective birth control, because
this study involves investigational agents whose genotoxic, mutagenic, and teratogenic
effects on the developing fetus and newborn are unknown. Therefore, for women of
childbearing potential only, a negative urine or serum pregnancy test pregnancy test
done =< 14 days prior to registration is required

REGISTRATION ELIGIBILITY CRITERIA:

- Patients without progressive disease per RECIST v 1.1 guidelines (i.e., with an
ongoing CR, PR or SD) following completion of 12-15 months of ICI treatment

- No toxicity from ICI therapy that makes continuation of treatment clinically
unacceptable

- Adequate bone marrow and organ functions to continue PD-1/L1 ICI as judged by the
treating physician

- Age >= 18 years

- Eastern Cooperative Oncology Group (ECOG) performance status 0-2

- Central nervous system (CNS) metastasis is allowed if radiographically stable,
clinically asymptomatic, and prior local therapy (if received) was completed > 6
months before registration

- No history of tuberculosis, active hepatitis B (HBV) or hepatitis C (HCV), or
uncontrolled human immunodeficiency virus (HIV)

- Patients with resolved HBV infection, defined as positive hepatitis B core
antibody (anti-Hb) and negative hepatitis B surface antigen (HbsAg), are eligible

- Patients with positive HCV antibody are eligible if HCV RNA PCR is negative

- Patients with HIV who are compliant with highly active antiretroviral therapy
(HAART) and have normal CD4 count and undetectable viral load are eligible

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