Infigratinib Before Surgery for the Treatment of Upper Tract Urothelial Cancer
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|ClinicalTrials.gov Identifier: NCT04228042|
Recruitment Status : Recruiting
First Posted : January 14, 2020
Last Update Posted : October 23, 2020
|Condition or disease||Intervention/treatment||Phase|
|Renal Pelvis and Ureter Urothelial Carcinoma||Drug: Infigratinib Other: Quality-of-Life Assessment Other: Questionnaire Administration Procedure: Surgical Procedure||Phase 1|
I. Evaluate the tolerability of infigratinib in patients with low-grade and high-grade platinum ineligible upper tract urothelial carcinoma (UTUC).
I. Assess tolerability in those with GFR 30-49. II. Evaluate the objective response rate (complete response [CR] + partial response [PR]) of infigratinib after 2 cycles in UTUC with and without FGFR3 alterations.
III. Correlate tumor tissue FGFR3 alteration (presence/absence, alteration type, and clonal status) with response and occurrence/severity of adverse events (AEs) such as hyperphosphatemia.
IV. Evaluate upper tract, bladder and local/distant recurrence within 12 months.
V. Evaluate renal function pre-treatment and after two treatments. VI. Evaluate patient-reported quality of life (QOL) outcomes during treatment.
I. Explore intra-tumor heterogeneity, gene expression profiles, and changes in tumor microenvironment using single cell ribonucleic acid (RNA) sequencing (scRNA-seq) and mass cytometry by time-of-flight (CyTOF) pre and post treatment to identify potential mechanisms of response and/or resistance, and correlation with the occurrence/severity of AEs.
II. Explore urinary/upper tract washing FGFR3 alterations as potential biomarker for detection and response.
III. Explore cell free deoxyribonucleic acid (cfDNA) for detection of FGFR3 alterations and as a predictor of response.
Patients receive infigratinib orally (PO) once daily (QD) on days 1-21. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. During weeks 8-9 (at least 48 hours after last dose of infigratinib), patients undergo surgery.
After completion of study treatment, patients are followed up at 30 days, then every 3 months for up to 1 year after surgery.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Tolerability and Activity of Neoadjuvant Infigratinib, an Inhibitor of FGFR, in Upper Tract Urothelial Carcinoma|
|Actual Study Start Date :||July 28, 2020|
|Estimated Primary Completion Date :||December 31, 2021|
|Estimated Study Completion Date :||December 31, 2021|
Experimental: Treatment (infigratinib, surgery)
Patients receive infigratinib PO QD on days 1-21. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. During weeks 8-9 (at least 48 hours after last dose of infigratinib), patients undergo surgery.
Other: Quality-of-Life Assessment
Other Name: Quality of Life Assessment
Other: Questionnaire Administration
Procedure: Surgical Procedure
- Incidence of adverse events [ Time Frame: Up to cycle 2 of infigratinib treatment (1 cycle = 28 days) ]Will estimate proportion of patients who are not able to complete treatment (discontinuation) due to excessive toxicity along with the 90% exact confidence interval. Toxicities will be tabulated using frequency and percentage by grade and their relations to treatment.
- Objective response [ Time Frame: After 2 cycles treatment of infigratinib (1 cycle = 28 days) ]Will estimate the objective response rate along with the 90% confidence interval. Fisher's exact test will be used to explore the difference in response between the two cohorts of patients.
- Circulating cell-free deoxyribonucleic acid (cfDNA) analysis [ Time Frame: Up to 1 year post surgery ]Wilcoxon rank sum test and Fisher's exact test will be used to explore the association between objective response and cfDNA.
- Expression of markers [ Time Frame: Up to 1 year post surgery ]Wilcoxon rank sum test and Fisher's exact test will be used to explore the association between objective response and expression of markers.
- FGFR3 alteration type [ Time Frame: Up to 1 year post surgery ]Wilcoxon rank sum test and Fisher's exact test will be used to explore the association between objective response and FGFR3 alteration type.
- Recurrence [ Time Frame: At 12 months ]Will be summarized using proportion and 90% confidence interval as a binary outcome, and will also be estimated using the Kaplan-Meier method as a time to event variable.
- Changes in patient reported quality of life outcomes [ Time Frame: Baseline up to 1 month postoperative check ]Will be measured using a validated questionnaire (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire version 3).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04228042
|Contact: Surena F. Matinfirstname.lastname@example.org|
|United States, Texas|
|M D Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Surena F. Matin 713-792-3250 email@example.com|
|Principal Investigator: Surena F. Matin|
|Principal Investigator:||Surena F Matin||M.D. Anderson Cancer Center|