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Advanced Urothelial CarcinomaPhase 1/2NCT04856189

Selinexor and Pembrolizumab for the Treatment of Cisplatin-Ineligible or Cisplatin-Refractory Locally Advanced or Metastatic Urothelial Carcinoma

A Phase 1/2 study testing Pembrolizumab and Selinexor in people with Advanced Urothelial Carcinoma and Locally Advanced Urothelial Carcinoma, run by Mamta Parikh at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This phase Ib/II trial finds the best dose of selinexor and its effect with pembrolizumab in treating patients with urothelial carcinoma that are not eligible to receive the chemotherapy drug cisplatin, or have been given cisplatin and the cancer has gotten worse. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Pembrolizumab and Selinexor
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
4 participants
Where
1 siteUnited States
Study dates
8 Apr 2021to 13 Feb 2024
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Pathologically confirmed locally advanced or metastatic urothelial carcinoma by histology
  • Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1
  • Not eligible to receive cisplatin-based chemotherapy due to renal dysfunction (defined as creatinine clearance [CrCl] =< 60 mL/min), > grade 2 peripheral neuropathy, or ototoxicity (defined as >= grade 2 hearing loss); OR unwillingness of patient to receive cisplatin; OR progressed on one platinum-based chemotherapy regimen for advanced disease
  • May have had neoadjuvant or adjuvant platinum-based chemotherapy or intravesical therapy in the past
  • >= 18 years of age
  • Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2
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  • Life expectancy >= 3 months
  • Absolute neutrophil count (ANC) >= 1 × 10^9/L
  • Platelet count >= 75 × 10^9/L (patients for whom <50% of bone marrow nucleated cells are plasma cells) or >= 50,000/mm3 (patients for whom >= 50% of bone marrow nucleated cells are plasma cells)
  • Hemoglobin >= 9 g/dL (may have been transfused)
  • Total bilirubin level =< 1.5 x the upper limit of normal (ULN) range (except patients with Gilbert's syndrome who must have a total bilirubin of < 3 x ULN)
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels =< 2.5 x ULN, or AST and ALT levels =< 5 x ULN (for subjects with documented metastatic disease to the liver)
  • Creatinine clearance >= 30 mL/min by Cockcroft-Gault formula
  • Subjects with active hepatitis B virus (Hep B) are allowed if antiviral therapy for hepatitis B has been given for > 8 weeks and viral load is < 100 IU/mL prior to first dose of trial treatment. Subjects with untreated hepatitis C virus (HCV) are allowed. Subjects with human immunodeficiency virus (HIV) who have CD4+ T-cell counts >= 350 cells/uL and no history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections in the last year are allowed
  • Willingness to undergo mandatory pre-treatment biopsy (unless there is adequate archival tumor specimen available for PD-L1 IHC evaluation)
  • Female subjects who are of non-reproductive potential (i.e., post-menopausal by history - no menses for >= 1 year; OR history of hysterectomy; OR history of bilateral tubal ligation; OR history of bilateral oophorectomy). Or, female subjects of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to the first study drug administration
  • Male and female subjects who are of reproductive potential must agree to use highly effective method of birth control (e.g., implants, injectables, birth control pills with two hormones, intrauterine devices [IUDs], complete abstinence or sterilized partner, and female sterilization) and a barrier method (e.g., condoms, vaginal ring, sponge, etc.) during the period of therapy and for 4 months after the last dose of study drug
  • Ability to understand and willingness to sign an informed consent form
  • Ability to adhere to the study visit schedule and other protocol requirements
  • Must be able to swallow study drug

Who cannot join

  • Receiving radiation =< 14 days prior to enrollment to the site of selected target lesions
  • Systemic therapy for cancer =< 21 days prior to enrollment
  • Autoimmune disorder requiring active therapy as defined by corticosteroids at a dose >= 10 mg oral prednisone or the equivalent or requiring chronic immunosuppressive therapy
  • Use of corticosteroids =< 14 days prior to enrollment at a dose of >= 10 mg oral prednisone or the equivalent per day
  • Received immune checkpoint inhibitor therapy (anti-PD-1, anti-PD-L1, or anti-CTLA4 directed therapy) on a prior clinical trial
  • Has received selinexor or another XPO1 inhibitor previously
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  • Any active gastrointestinal dysfunction that could interfere with absorption of study treatment in the opinion of the investigator
  • Pregnant or lactating women
  • Any condition that would prohibit the understanding or rendering of informed consent
  • Any condition including additional malignancies, laboratory abnormalities, or psychiatric illness that in the opinion of the investigator would interfere with the patient's safety or compliance while on trial
  • Severe infection that in the opinion of the investigator would interfere with patient safety or compliance on trial within 4 weeks prior to enrollment

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of California Davis Comprehensive Cancer Center

    Sacramento, California, 95817

Other trials in United States

About this study

Official title: A Phase Ib/II Study of Selinexor Plus Pembrolizumab in Cisplatin-Ineligible or Cisplatin-Refractory Patients With Advanced Urothelial Carcinoma

This phase Ib/II trial finds the best dose of selinexor and its effect with pembrolizumab in treating patients with urothelial carcinoma that are not eligible to receive the chemotherapy drug cisplatin, or have been given cisplatin and the cancer has gotten worse. Patients must also have urothelial carcinoma that has spread locally, near where it started (locally advanced), or has spread to other parts of the body (metastatic). Selinexor may stop the growth of tumor cells by blocking a protein, called XPO1, that is needed for cell growth. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving selinexor and pembrolizumab may kill more tumor cells.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the recommended phase 2 dose (RP2D) of selinexor in combination with standard-dose pembrolizumab in patients with advanced urothelial carcinoma who are cisplatin-ineligible or platinum-refractory. (Phase Ib) II. To determine the objective response rate (ORR) of selinexor in combination with pembrolizumab in patients with advanced urothelial carcinoma who are cisplatin-ineligible or platinum-refractory. (Phase II)

SECONDARY OBJECTIVES:

  1. To further evaluate the toxicity profile of the combination of selinexor with pembrolizumab in patients with advanced urothelial carcinoma.

II. To further evaluate the efficacy of the combination of selinexor with pembrolizumab in patients with advanced urothelial carcinoma as defined by progression-free survival (PFS).

Being tested
Pembrolizumab, Selinexor
Medical subject headings
Carcinoma, Transitional Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PembrolizumabBiological

    Also called Keytruda, Lambrolizumab, MK-3475, SCH 900475

    Given IV

  • SelinexorDrug

    Also called ATG-010, CRM1 Nuclear Export Inhibitor KPT-330, KPT-330, Selective Inhibitor of Nuclear Export KPT-330

    Given PO

Study groups in NCT04856189
Study groupRoleWhat they receive
Treatment (selinexor, pembrolizumab)ExperimentalPatients receive selinexor PO on days 1, 8 and 15, and pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days for 24 months in the absence of disease progression or unacceptable toxicity.
Receives: Biological: Pembrolizumab; Drug: Selinexor

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Recommended Phase 2 Dose (RP2D) (Phase Ib)

    Defined by dose-limiting toxicity (DLTs). Dose limiting toxicities will be listed according to dose level. Separately by dose level and the expansion cohort (as well as for the total RP2D cohort), adverse events (AEs) will be summarized as number of patients according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 term and grade, where grade is the maximum across a patient's treatment period.

    Measured: Up to 2 cycles (each cycle is 21 days); up to about 6 weeks

  2. Objective Response Rate (ORR) (Phase II)

    ORR, calculated as the total number of patients with a confirmed complete response or partial response, will be reported as a percentage of total evaluable patients. Response will be reported using Response Evaluation Criteria in Solid Tumor 1.1 definitions. ORR will be summarized by exact binomial 95% confidence intervals (CI).

    Measured: Up to approximately 2 years 4 months

Secondary outcomes (2)

  1. Number of Patients Who Experience a Grade 3 or Higher Adverse Event (AE).

    Defined by NCI CTCAE version 5. The number of patients who experience at least one grade 3-5 AEs will be reported.

    Measured: Up to approximately 1 year 7 months.

  2. Progression-free Survival (PFS)

    Progression-free survival (PFS) defined as the median time from initiation of study intervention to progressive disease, defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0).

    Measured: From enrollment to trial to time of disease progression or death from any cause, assessed up to 2 year 4 months.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Apr 2021
  2. Study start8 Apr 2021
  3. Primary completion4 Jan 2024
  4. Study completion13 Feb 2024

Why it stopped: Poor accrual.

Resources

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
Masking
None (open label)
Enrolment
4 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04856189
Sponsor's protocol ID
UCDCC#289
Other IDs
NCI-2021-02845, UCDCC#289, P30CA093373
Status last verified
Jan 2026
First submitted
19 Apr 2021
Last updated
29 Jan 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Pembrolizumab and Selinexor in people with Advanced Urothelial Carcinoma and Locally Advanced Urothelial Carcinoma, run by Mamta Parikh at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 29 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 29 Jan 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Recommended Phase 2 Dose (RP2D) (Phase Ib) (time frame: Up to 2 cycles (each cycle is 21 days); up to about 6 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04856189.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jan 2026.

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