Combination of selinexor and pembrolizumab for advanced urothelial carcinoma treatment
A Phase Ib/II Study of Selinexor Plus Pembrolizumab in Cisplatin-Ineligible or Cisplatin-Refractory Patients With Advanced Urothelial Carcinoma
This study is testing if a new combination of selinexor and pembrolizumab can help people with advanced bladder cancer who can't take cisplatin or whose cancer got worse after using it.
Quick facts
| Phase | Phase1; Phase2 |
|---|---|
| Study type | Interventional |
| Enrollment | 12 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | University of California, Davis Academic / other |
| Drugs / interventions | chemotherapy, radiation, prednisone, pembrolizumab, Immunotherapy |
| Locations | 1 site (Sacramento, California) |
| Trial ID | NCT04856189 on ClinicalTrials.gov |
What this trial studies
This trial investigates the effectiveness of selinexor in combination with pembrolizumab for patients with locally advanced or metastatic urothelial carcinoma who cannot receive cisplatin or have experienced disease progression after cisplatin treatment. The study aims to determine the optimal dose of selinexor and evaluate its impact on tumor response rates and progression-free survival. By blocking a specific protein involved in cell growth and enhancing the immune response against cancer, this combination therapy seeks to improve treatment outcomes for these patients.
Who should consider this trial
Good fit: Ideal candidates include adults with pathologically confirmed locally advanced or metastatic urothelial carcinoma who are cisplatin-ineligible or have progressed after cisplatin treatment.
Not a fit: Patients who are eligible for cisplatin-based chemotherapy or have other types of cancer may not benefit from this study.
Why it matters
Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced urothelial carcinoma who are ineligible for cisplatin-based chemotherapy.
How similar studies have performed: Other studies have shown promising results with similar immunotherapy approaches, but the combination of selinexor and pembrolizumab in this specific patient population is relatively novel.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * 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 * 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 Exclusion Criteria: * 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 * 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
Where this trial is running
Sacramento, California
- University of California Davis Comprehensive Cancer Center — Sacramento, California, United States (Recruiting)
Study contacts
- Principal investigator: Mamta Parikh — University of California, Davis
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.