TAS-102 in Treating Patients with Locally Advanced Unresectable or Metastatic Bladder Cancer
- 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 (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm (>= 2 cm) with conventional techniques or as >= 10 mm (>= 1 cm) with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam. Tumor lesions that are situated in a previously irradiated area will not be considered measurable
- 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 (PD-1 or PD-L1 antibody) inhibitor or ineligible to receive check-point inhibitor
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
- Absolute neutrophil count >= 1,500/mcL
- Platelets >= 75,000/mcL
- Total bilirubin =< 1.5 x institutional upper limit of normal
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x institutional upper limit of normal
- Creatinine clearance >= 40 mL/min/1.73 m^2 calculated by the Cockcroft-Gault formula
- If liver function abnormalities are due to underlying liver metastases, then the following criteria will be used: * AST (SGOT) =< 5 x upper limit of normal (ULN) * ALT (SGPT) =< 5 x ULN
- 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 (hormonal AND barrier method of birth control) prior to study entry, for the duration of study participation, and for 6 months following completion of therapy. If a woman becomes pregnant or suspects she is pregnant while participating in this study, she should inform her treating physician immediately
- 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
- Patients who have had chemotherapy or radiotherapy within 4 weeks (prior to enrollment/registration)
- Patients with prior therapy-induced adverse events (AEs) not recovered to =< grade 2
- 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). Pregnant women are excluded from this study because TAS-102 is an agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother withTAS-102, breastfeeding should be discontinued if the mother is treated with TAS-102
- Patients with known brain metastases are excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to TAS-102
- Patients with human immunodeficiency virus (HIV) on anti-retro-viral therapy with thymidine kinase substrates, e.g. stavudine, zidovudine, telbivudine. Known HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with TAS-102. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy
- 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
- Checkpoint inhibitor ineligibility will be defined as patients with: * Active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic or immunosuppressive agents, or * Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy, or * Patient deemed not to be a candidate for immunotherapy based on the discretion of the treating physician due to co-morbidities which preclude them from receiving immunotherapy
I. Clinical benefit rate (complete response + partial response + stable disease) at 6 months.
I. Progression-free survival including PFS at 6 months (PFS6).
II. Overall response rate (ORR).
III. Overall survival (OS).
IV. Quality of life.
V. Safety and tolerability.
VI. Participant reported outcomes using standardized questionnaires.
VII. Participant activity and sleep status using wearable wireless tracking devices.
I. Quantifying deoxyribonucleic acid (DNA) damage measuring phosphorylated (p)ATM and gamma-H2AX in peripheral blood mononuclear cells (PBMCs).
II. Measurement of DNA glycosylase levels.
Patients receive trifluridine and tipiracil hydrochloride orally (PO) twice daily (BID) on days 1-5 and 8-12. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days and 6 months.
Trial Phase Phase II
Trial Type Treatment
University of Kansas Cancer Center
Rahul A. Parikh
- Primary ID IIT-2018-TAS-102
- Secondary IDs NCI-2019-00336
- Clinicaltrials.gov ID NCT03762161