VA Office of Research and Development
This study aims to determine whether adding an oral medication called Capivasertib to ongoing immunotherapy can enhance treatment responses in patients with advanced bladder cancer (aBC), as well as to evaluate the safety of this combination. Capivasertib is an anti-cancer drug approved by the U.S. Food and Drug Administration (FDA) for breast cancer, but it is not approved for aBC and, in this study, will be used as an investigational agent. Immunotherapy is FDA-approved for aBC, yet while some patients respond, others either do not benefit or develop resistance after an initial response. Previous research indicates that drugs similar to Capivasertib may increase the effectiveness of immunotherapy. Therefore, this study will enroll patients whose aBC no longer responds to immunotherapy, add Capivasertib to their treatment regimen, and monitor for improvements in immune response against aBC and any potential side effects associated with the combination therapy.
This study will enroll patients with advanced bladder cancer who have previously received an immune checkpoint inhibitor (ICI) or ICI-based therapy and whose cancer is no longer responding to treatment. In this trial, patients will continue their ICI therapy while capivasertib is added to their regimen. Participants will be closely monitored to assess whether the addition of capivasertib enhances the cancer's response to ICI therapy and to evaluate the safety and potential toxicities of the combination treatment.
Inclusion Criteria: 1. Male or female patients are eligible 2. Diagnosis of urothelial carcinoma, with mixed histology permitted: 1. Histologically or cytologically confirmed advanced or recurrent urothelial carcinoma, OR 2. Documented Stage IV disease (T4b, Any N, M0; any T, Any N, M1a-b), Stage IIIB (T1-T4a, N2-N3, M0), or a subset of Stage IIIA (T1-T4a, N1, M0) 3. Genomic testing, including assessment for PIK3CA, AKT1, or PTEN alterations, must have been performed 4. Patients must have stable disease or cancer progression after at least 12 weeks of Immune Checkpoint Inhibitors (ICI)…
Patients will continue their ICI treatment, with capivasertib added at a dose of 400 mg orally twice daily, administered on a schedule of 4 days on followed by 3 days off, continuously throughout the study period.