A Phase II Study of Lonsurf (TAS-102) in Metastatic Platinum and Checkpoint Inhibitor-resistant Bladder Cancer

A Phase II Study of TAS-102 in Metastatic Platinum and Checkpoint Inhibitor-resistant Bladder Cancer

This study evaluates the clinical benefit of TAS-102 in participants with metastatic urothelial carcinoma who are resistant to cisplatin or carboplatin front-line and checkpoint inhibitors as second line therapy. All participants will receive TAS-102 in oral form twice per day on Days 1-5 and Days 8-12 of each 28 day cycle.

Study Overview

• Status: Recruiting
• Conditions: Bladder Cancer
• Intervention / Treatment: Drug: TAS 102

• Study Type: Interventional
• Enrollment (Anticipated): 22
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Fairway, Kansas, United States, 66208
      • Recruiting
      • University of Kansas Cancer Center - Clinical Research Center
    • Kansas City, Kansas, United States, 66205
      • Recruiting
      • University of Kansas Cancer Center, Westwood Campus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Ability of participant to understand this study, and participant willingness to sign a written informed consent.
• Participants must have histologically or cytologically confirmed locally advanced unresectable or metastatic urinary bladder (urothelial) cancer. Participants with mixed histologies are permitted as long as transitional cell carcinoma is present in the pathological specimen.
• Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension
• Documented progression on or within 12 months of treatment with one previous platinum-containing regimen or ineligible to receive platinum-containing regimen. Neo-adjuvant or adjuvant platinum-based chemotherapy will be deemed to be first-line when participants progressed within 12 months of the last dose
• Documented progression on prior checkpoint inhibitor or ineligible to receive check-point inhibitor
• Adequate performance status, organ, and marrow function.
• Women of child-bearing potential and men with partners of child-bearing potential must agree to practice sexual abstinence, or to use two forms of adequate contraception.
• Men of child-bearing potential must not father a child or donate sperm while on this study and for 6 months after their last study treatment

Exclusion Criteria:

• Patients who have had chemotherapy or radiotherapy within 4 weeks of enrollment/registration.
• Current or anticipated use of other investigational agents while participating in this study.
• Psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant or breast feeding (if applicable).
• Patients with known brain metastases
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to TAS 102.
• Patients with HIV on anti-retro-viral therapy with thymidine kinase substrates, for example, stavudine, zidovudine, telbivudine.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia. Undergoing active treatment for a co-existing malignancy with the exception of adequately treated basal cell carcinoma, squamous cell skin cancer, thyroid cancer or incidental prostate adenocarcinoma detected at radical cystectomy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention TAS-102	Drug: TAS 102; Participant self-administered orally at 35 milligrams per meter squared (mg/m2) twice daily Days 1-5 and 8-12 of every 28 day cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical benefit rate (complete response+ partial response+ stable disease)	Evaluated per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1	Up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival rate (PFS) among participants	Evaluated per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1	Up to 6 months
Overall response rate (ORR) among participants	Evaluated per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1	Up to 12 months
Overall survival rate (OS) among participants	Evaluated per Medical Record	Up to 12 months
Overall change in patient-reported quality of life outcomes	Evaluated per Functional Assessment of Cancer Therapy - Bladder (FACT-Bl) version 4 - quality of life (QOL) questionnaire scores; FACT-Bl total score range is 0-156, derived by the sum of the sub-scales. Higher scores indicate better QOL.; FACT-Bl includes five sub-scales:Physical Well-being (PWB), score range of 0-28Social/Family Well-being (SWB), score range of 0-28Emotional Well-being (EWB), score range of 0-24Functional Well-being (FWB), score range of 0-28Bladder Cancer Subscale (BlCS), score range of 0-48; Note: Negatively stated items are reversed by subtracting the response from "4".	Up to 26 months
Proportion of participants with Grade 3 or higher Adverse and Serious Adverse Events	Evaluated per Common Terminology Criteria for Adverse Events (CTCAE) v5.0	Up to 26 months

Collaborators and Investigators

• Sponsor: Rahul Parikh
• Collaborators: Taiho Oncology, Inc.
• Investigators: Principal Investigator: Rahul Parikh, MD, The University of Kansas Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): January 3, 2019
• Primary Completion (Anticipated): July 1, 2023
• Study Completion (Anticipated): January 1, 2024

Study Registration Dates

• First Submitted: November 30, 2018
• First Submitted That Met QC Criteria: November 30, 2018
• First Posted (Actual): December 3, 2018

Study Record Updates

• Last Update Posted (Actual): March 10, 2022
• Last Update Submitted That Met QC Criteria: March 9, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Urinary Bladder Diseases; Urinary Bladder Neoplasms
• Other Study ID Numbers: IIT-2018-TAS-102

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No