Advanced Urothelial CarcinomaPhase 1/2NCT07793578
Immunotherapy Plus Capivasertib for Metastatic Bladder Cancer
A Phase 1/2 study testing capivasertib in people with Advanced Urothelial Carcinoma, run by VA Office of Research and Development at 4 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Urothelial Carcinoma
- What is being tested?
- capivasertib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 4 sitesUnited States
- Study dates
- 1 Jan 2027to 30 Sep 2030
- Phase
- Phase 1/2
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
- Male or female patients are eligible
- Diagnosis of urothelial carcinoma, with mixed histology permitted:
- Histologically or cytologically confirmed advanced or recurrent urothelial carcinoma, OR
- 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)
- Genomic testing, including assessment for PIK3CA, AKT1, or PTEN alterations, must have been performed
- Patients must have stable disease or cancer progression after at least 12 weeks of Immune Checkpoint Inhibitors (ICI) or ICI-based therapy, per RECIST v1.1 guidelines
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- Patients must have received prior enfortumab vedotin unless contraindicated
- Patients must be asymptomatic or minimally symptomatic from metastatic urothelial cancer
- Willingness to receive ICI in combination with capivasertib during the study is required. If cancer progressed on an ICI plus another anti-cancer drug(s) (e.g., pembrolizumab plus enfortumab vedotin), the additional drug(s) must be discontinued for at least 14 days, while ICI is continued, prior to starting capivasertib.
- Patients must have no or only minimal and stable adverse events from prior cancer-directed therapy, including ICI
- Measurable disease is required:
- X-rays, CT/MRI, or physical exams must have been performed within 28 days before starting study medications
- At least one measurable lesion per RECIST 1.1 must be present at baseline (≥10 mm in longest diameter, or lymph nodes with a short axis ≥15 mm, using CT or MRI; previously irradiated lesions are excluded)
- Tumor samples:
- Baseline biopsy prior to treatment is strongly recommended, unless it poses excessive risk
- When biopsied, in addition to FFPE preparation, fresh tissue should be sent to VABHS for single-cell RNA sequencing and T-cell receptor sequencing
- If baseline biopsy is not feasible, the most recent FFPE tumor tissue block from primary or metastatic sites should be obtained; if the block is unavailable, 15 (minimum 10) unstained slides are acceptable
- If biopsy is deemed too risky, participation may proceed without new tissue.
- Estimated life expectancy of at least 3 months
- ECOG performance status ≤2 OR Karnofsky ≥60%. For the safety lead-in phase, only ECOG PS 0-1 patients will be included
- Adequate bone marrow function, without recent transfusions or growth factor support (within 14 days prior to first dose):
- Absolute neutrophil count > 1,000/cubic millimeters (mm³)
- Hemoglobin ≥ 9.0 grams (g)/deciliter (dL)
- Platelets > 100,000/mm³
- Adequate renal function: Estimated creatinine clearance ≥30 milliliter (mL)/minute (Cockcroft-Gault equation, actual weight), with no need for chronic dialysis. No capivasertib dose adjustment required if clearance ≥30 mL/minute
- Adequate liver function:
- Total bilirubin ≤1.5 × upper limit of normal value (ULN), or ≤3 × ULN for documented Gilbert's syndrome.
- AST and ALT ≤2.5 × ULN (or ≤5 × ULN for hepatic metastases).
- For females of childbearing potential: Negative serum pregnancy test at screening.
- Male patients able to father children, and females of childbearing potential, must agree to use two highly effective contraceptive methods throughout the study and for at least 16 weeks after the last dose of capivasertib
- Signed and dated informed consent indicating the patient has been fully informed about the study
- Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and all other study procedures
Who cannot join
- Patients who have undergone major surgery within 4 weeks, or major radiation therapy within 2 weeks, prior to starting treatment. Prior palliative radiotherapy is permitted if completed at least 48 hours before study entry
- Receipt of another investigational agent within the past 4 weeks. Participation in observational studies is allowed
- Persistent toxicities (CTCAE Grade ≥2) from previous anticancer therapy, except for alopecia. Patients with irreversible toxicity not reasonably expected to be exacerbated by study intervention (as deemed by the investigator, such as hearing loss) may be included.
- Refractory nausea and vomiting, chronic gastrointestinal disease, inability to swallow capivasertib, or prior significant bowel resection that may impair adequate absorption, distribution, metabolism, or excretion of capivasertib.
- Active tuberculosis infection, as determined by clinical evaluation, imaging, or tuberculosis testing per local practice
- Prior treatment with a phosphoinositide 3-kinase (PI3K) inhibitor
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- Known or suspected hypersensitivity to study drugs or any of their components
- Spinal cord compression or brain metastases, unless asymptomatic, stable, and not requiring steroids for at least 4 weeks prior to study intervention. Patients with previously treated CNS metastases may be eligible if they have recovered from acute effects of radiation or surgery, discontinued corticosteroids for at least 4 weeks, and are neurologically stable
- Diagnosis of any other malignancy within the past 3 years, except adequately treated basal or squamous cell skin cancer, other Stage 0 or 1 cancers, or incidental prostate cancer found at cystoprostatectomy
- Moderate to severe symptoms from metastatic cancer, including moderate to severe pain, impaired organ function, or spinal cord compression
- Active autoimmune disease likely to worsen with ICI therapy. Patients with vitiligo, psoriasis, or thyroid disorders controlled without immunosuppressive therapy are eligible
- Known severe hypersensitivity reactions (Grade >3) to monoclonal antibodies, history of anaphylaxis, or uncontrolled asthma
- History or concurrent condition of interstitial lung disease or severely impaired lung function, as judged by the investigator
- Any of the following cardiac risks:
- Mean resting corrected QT interval (QTc) >470 milliseconds (ms) from triplicate ECGs at screening
- History of QT prolongation due to medication requiring discontinuation
- Congenital long QT syndrome, family history of long QT, or unexplained sudden cardiac death under age 40 in first-degree relatives
- Significant arrhythmias (e.g., symptomatic or CTCAE Grade 3 PVCs, bigeminy, trigeminy, ventricular tachycardia), uncontrolled or symptomatic atrial fibrillation, unless well-controlled by medication or device (investigator and cardiologist review recommended)
- Clinically significant electrolyte abnormalities linked to QTc prolongation: hypokalemia, hypomagnesemia, hypocalcemia
- Any other condition(s) significantly increasing QTc prolongation risk per investigator judgment
- History of coronary artery bypass, angioplasty, myocardial infarction, or unstable angina in the prior 3 months
- Congestive heart failure (NYHA class ≥2)
- Clinically significant abnormalities of glucose metabolism, including:
- Type 1 or insulin-dependent type 2 diabetes
- HbA1c > 8.0%
- Current or prior use of immunosuppressive medications within 7 days before study start, except: a. Intranasal, inhaled, topical steroids, or local injections (e.g., intra-articular) b. Systemic corticosteroids up to 10 mg/day of prednisone or equivalent c. Steroids as premedication for hypersensitivity (e.g., CT scan premedication)
- Active bleeding diathesis.
- Active infection requiring systemic therapy.
- Positive for HIV infection or known AIDS, due to potential pharmacokinetic interactions with capivasertib.
- Hepatitis B (positive surface antigen) or hepatitis C (positive HCV RNA if antibody positive).
- Any other disease, condition, or laboratory abnormality which, in the investigator's opinion, may confound study results, increase the risks of study complications, contraindicate investigational drug use, or interfere with informed consent
- Vaccination with live, attenuated, or unknown-status vaccines within 4 weeks of first study treatment or during the trial (except inactivated vaccines, e.g., inactivated influenza and COVID-19 vaccines)
- Pregnancy, breastfeeding, or unwillingness/inability of female patients of childbearing potential and male patients to use two highly effective contraceptive methods throughout the study and for at least 16 weeks after the last dose of capivasertib
- History of noncompliance with medical regimens
- Unwillingness or inability to comply with study protocol
Trial locations and contacts
4 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States4 sites
VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA
Boston, Massachusetts, 02130-4817
Colleen Hynes, BS, (857) 720-5501, Colleen.Hynes@va.gov
Chong-Xian Pan, MD PhD
Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA
Philadelphia, Pennsylvania, 19104-4551
Yu-Ning Wang, MD, Yu-Ning.Wong@va.gov
VA Puget Sound Health Care System Seattle Division, Seattle, WA
Seattle, Washington, 98108-1532
Robert B Montgomery, MD, Robert.Montgomery@va.gov
VA Connecticut Healthcare System West Haven Campus, West Haven, CT
West Haven, Connecticut, 06516-2770
Yu Zhang, MD, Yu.Zhang2@va.gov
About this study
Official title: A Phase Ib/Phase II Trial With Capivasertib Plus Immunotherapy in Bladder Cancer
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.
Read the detailed description
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.
- Conditions
- Advanced Urothelial Carcinoma
- Being tested
- capivasertib
- Keywords
- advanced urothelial carcinoma, immune checkpoint inhibitor, PI3K/AKT, capivaseretib
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
capivasertibDrug
Also called Truqap
Patients will continue their immune checkpoint inhibitor (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.
| Study group | Role | What they receive |
|---|---|---|
| treatment | Experimental | Patients will continue immune checkpoint inhibitor (ICI) treatment and capivasertib will be added Receives: Drug: capivasertib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective response rate (ORR)
ORR is defined as the percentage of patients who have a partial or complete response at any time during the treatment of this trial.
Measured: through study completion, an average of 1 year
Secondary outcomes (5)
Progression-free survival (PFS)
PFS is defined as the time between initiation of the ICI/capivasertib combination treatment and tumor progression or death from any cause, with censoring of patients who are lost to follow-up
Measured: through study completion, an average of 1 year
Overall survival (OS)
OS is defined as the length of time from the start of this trial treatment to the time of death from any cause, with censoring of patients who are lost to follow-up.
Measured: through study completion, an average of 1.5 year
Disease control rate (DCR)
DCR is the percentage of patients who have a partial or complete response or stable disease at any time during this treatment of this trial.
Measured: through study completion, an average of 1 year
Safety
Safety will be determined by percentage of patients who develop adverse events (AEs) during the study. AEs will be graded on a 1-5 scale based on the Common Terminology Criteria for Adverse Events (CTCAE).
Measured: through study completion, an average of 1 year
Tolerability
Tolerability will be determined based on percentage of patients who have study drug dose reduction or discontinuation during the study secondary of adverse events.
Measured: through study completion, an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Aug 2026
- Study start1 Jan 2027 (estimated)
- Primary completion30 Sep 2029 (estimated)
- Study completion30 Sep 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Urothelial CarcinomaStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- All patients will continue ICI treatment and capivasertib will be added to the ongoing ICI treatment
- Masking
- None (open label)
- Enrolment
- 32 participants (estimated)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Chong-Xian Pan, MD PhD, Principal investigator, VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07793578
- Sponsor's protocol ID
- SPLP-001-25F
- Other IDs
- VA ORD
- Status last verified
- Sep 2026
- First submitted
- 19 Aug 2026
- Last updated
- 5 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Aggregated data without any identifiable information will be shared.