RECRUITING

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

Conditions

Advanced Urothelial Carcinoma Locally Advanced Urothelial Carcinoma Metastatic Urothelial Carcinoma Refractory Urothelial Carcinoma

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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

Quick Facts

Study Start:2021-04-08

Study Completion:2024-05-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04856189

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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	* 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

Inclusion Criteria

Exclusion 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

* 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

Contacts and Locations

Principal Investigator

Mamta Parikh

PRINCIPAL_INVESTIGATOR

University of California, Davis

Study Locations (Sites)

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817

United States

Collaborators and Investigators

Sponsor: Mamta Parikh

Mamta Parikh, PRINCIPAL_INVESTIGATOR, University of California, Davis

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2021-04-08

Study Completion Date2024-05-01

Study Record Updates

Study Start Date2021-04-08

Study Completion Date2024-05-01

Terms related to this study

Additional Relevant MeSH Terms

Advanced Urothelial Carcinoma
Locally Advanced Urothelial Carcinoma
Metastatic Urothelial Carcinoma
Refractory Urothelial Carcinoma