Trial Outcomes & Findings for Infigratinib Before Surgery for the Treatment of Upper Tract Urothelial Cancer (NCT NCT04228042)

Last Updated: 2025-01-01

Results Overview

The study will estimate percentage of patients who are not able to complete treatment (discontinuation) due to excessive toxicity along with the 90% exact confidence interval (NOTE: excessive toxicity is defined as treatment related adverse events that cause patients not to complete 2-cycles of planned treatment schedule, or delay in planned surgery greater than 14 days)

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

15 participants

Primary outcome timeframe

From day 1 until 30 days following last dose of infigratinib or until surgery, whichever occurs last, up to a total of 3 months.

Results posted on

2025-01-01

Participant Flow

The study was written to enroll and treat 20 participants, but enrollment was stopped because the drug manufacturer made the business decision to cease all infigratinib oncology research in the US and withdrew the IND that we cross-referenced in this IIT. Ultimately, 15 participants were consented, 1 patient screen failed, 14 completed the study

Participant milestones

Participant milestones
Measure	Infigratinib Plus Surgery Patients will receive infigratinib 125 mg orally every day for a total of 2 cycles followed by surgery.
Overall Study STARTED	14
Overall Study COMPLETED	14
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Infigratinib Before Surgery for the Treatment of Upper Tract Urothelial Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Infigratinib Plus Surgery n=14 Participants Patients will receive infigratinib 125 mg orally every day for a total of 2 cycles followed by surgery.
Age, Categorical <=18 years	0 Participants n=99 Participants
Age, Categorical Between 18 and 65 years	8 Participants n=99 Participants
Age, Categorical >=65 years	6 Participants n=99 Participants
Age, Continuous	63 years n=99 Participants
Sex: Female, Male Female	2 Participants n=99 Participants
Sex: Female, Male Male	12 Participants n=99 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=99 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	12 Participants n=99 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants
Race (NIH/OMB) Asian	0 Participants n=99 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants
Race (NIH/OMB) Black or African American	1 Participants n=99 Participants
Race (NIH/OMB) White	13 Participants n=99 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants

PRIMARY outcome

Timeframe: From day 1 until 30 days following last dose of infigratinib or until surgery, whichever occurs last, up to a total of 3 months.

Population: All patients who received at least one dose of infigratinib and completed surgery were included in the anlaysis. There were no delays to planned surgery in any of the participants

Outcome measures

Outcome measures
Measure	Infigratinib Plus Surgery n=14 Participants Patients will receive infigratinib 125 mg orally every day for a total of 2 cycles followed by surgery.
Safety and Tolerability - TOX Rate	14.30 percentage of patients Interval 2.6 to 38.5

SECONDARY outcome

Timeframe: Efficacy will be measured at time of surgery or approximately 2 months

Percentage of patients achieving a point in time objective response (either complete or partial response \[CR or PR\]) after 2 cycles of infigratinib. Tumor mapping will be performed from the endoscopic evaluation (after any biopsies) and this will be used to compare to pathologic (NUx/Ux cohort) or ureteroscopic (endoscopy cohort) findings in order to determine responses. Tumor mapping will be performed based on endoscopic findings, noting location, number of tumors, tumor architecture, and location of biopsies; and will again be performed during pathologic evaluation again noting size, location, number of tumors, architecture, and absence of tumor at any previously identified tumor. A difference of 3mm will be considered within error of measurement. All analyses will be performed on patients stratified as having or not having FGFR3 alterations.

Outcome measures

Outcome measures
Measure	Infigratinib Plus Surgery n=14 Participants Patients will receive infigratinib 125 mg orally every day for a total of 2 cycles followed by surgery.
Evaluate the Objective Response Rate (CR+PR) of Infigratinib After 2 Cycles in UTUC With and Without FGFR3alterations	66.7 percentage of participants Interval 34.5 to 90.2

SECONDARY outcome

Timeframe: QoL surveys were obtained at baseline (day 1), pre-op after having received infigratinib for 2 cycles and 30 days after surgery, up to 3 months

Categorical variables were tabulated with frequency and percentage; continuous variables were summarized using descriptive statistics. A linear transformation to standardize the raw score was calculated for Functional/symptom scales and global health status (QOL) using the guidance in Scoring the EORTC QLQ-C30 version 3.0, so that scores range from 0 to 100. A higher score represents a higher ("better") level of functioning, or a higher ("worse") level of symptoms. Wilcoxon signed rank test was applied to compare functional/symptom scales and global health status (QOL) between different time points. A higher score for symptoms represents a worse outcome.

Outcome measures

Outcome measures
Measure	Infigratinib Plus Surgery n=14 Participants Patients will receive infigratinib 125 mg orally every day for a total of 2 cycles followed by surgery.
To Evaluate Patient-reported Quality of Life (QOL) Fatigue score: post-OP	15.08 score on a scale Standard Deviation 20.26
To Evaluate Patient-reported Quality of Life (QOL) Scores of appetite loss: 30 days Post-OP	7.14 score on a scale Standard Deviation 14.19
To Evaluate Patient-reported Quality of Life (QOL) Fatigue score: Pre-OP	17.46 score on a scale Standard Deviation 12.1
To Evaluate Patient-reported Quality of Life (QOL) Score of diarrhea: At screening	12.82 score on a scale Standard Deviation 21.68
To Evaluate Patient-reported Quality of Life (QOL) Score of diarrhea: Pre-OP	12.80 score on a scale Standard Deviation 16.88
To Evaluate Patient-reported Quality of Life (QOL) Scores of appetite loss: At screening	4.76 score on a scale Standard Deviation 12.1
To Evaluate Patient-reported Quality of Life (QOL) Scores of appetite loss: Pre-OP	19.05 score on a scale Standard Deviation 21.54

Adverse Events

Infigratinib Plus Surgery

Serious events: 1 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Infigratinib Plus Surgery n=14 participants at risk Patients will receive infigratinib 125 mg orally every day for a total of 2 cycles followed by surgery.
Investigations Hyponatremia	7.1% 1/14 • From day 1 until 30 days following last dose of infigratinib or until surgery, whichever occurs last, up to a total of 3 months.

Other adverse events

Other adverse events
Measure	Infigratinib Plus Surgery n=14 participants at risk Patients will receive infigratinib 125 mg orally every day for a total of 2 cycles followed by surgery.
Investigations Hyperphosphatemia	64.3% 9/14 • Number of events 9 • From day 1 until 30 days following last dose of infigratinib or until surgery, whichever occurs last, up to a total of 3 months.
Investigations Hyponatremia	14.3% 2/14 • Number of events 2 • From day 1 until 30 days following last dose of infigratinib or until surgery, whichever occurs last, up to a total of 3 months.
Investigations Lipase Increase	21.4% 3/14 • Number of events 3 • From day 1 until 30 days following last dose of infigratinib or until surgery, whichever occurs last, up to a total of 3 months.
Investigations Amylase Increase	14.3% 2/14 • Number of events 2 • From day 1 until 30 days following last dose of infigratinib or until surgery, whichever occurs last, up to a total of 3 months.
Investigations Hyperkalemia	14.3% 2/14 • Number of events 2 • From day 1 until 30 days following last dose of infigratinib or until surgery, whichever occurs last, up to a total of 3 months.
Investigations Creatinine Increase	14.3% 2/14 • Number of events 2 • From day 1 until 30 days following last dose of infigratinib or until surgery, whichever occurs last, up to a total of 3 months.
Investigations BUN Increase	7.1% 1/14 • Number of events 1 • From day 1 until 30 days following last dose of infigratinib or until surgery, whichever occurs last, up to a total of 3 months.
Investigations Cytokine Release Syndrome	7.1% 1/14 • Number of events 1 • From day 1 until 30 days following last dose of infigratinib or until surgery, whichever occurs last, up to a total of 3 months.
Investigations Anemia	7.1% 1/14 • Number of events 1 • From day 1 until 30 days following last dose of infigratinib or until surgery, whichever occurs last, up to a total of 3 months.
Investigations Hypercalcemia	7.1% 1/14 • Number of events 1 • From day 1 until 30 days following last dose of infigratinib or until surgery, whichever occurs last, up to a total of 3 months.
Investigations Hypophosphatemia	7.1% 1/14 • Number of events 1 • From day 1 until 30 days following last dose of infigratinib or until surgery, whichever occurs last, up to a total of 3 months.
Investigations WBC Decreased	7.1% 1/14 • Number of events 1 • From day 1 until 30 days following last dose of infigratinib or until surgery, whichever occurs last, up to a total of 3 months.
Investigations ALT Increase	14.3% 2/14 • Number of events 2 • From day 1 until 30 days following last dose of infigratinib or until surgery, whichever occurs last, up to a total of 3 months.
Investigations AST Increase	7.1% 1/14 • Number of events 1 • From day 1 until 30 days following last dose of infigratinib or until surgery, whichever occurs last, up to a total of 3 months.
Gastrointestinal disorders Diarrhea	50.0% 7/14 • Number of events 7 • From day 1 until 30 days following last dose of infigratinib or until surgery, whichever occurs last, up to a total of 3 months.
Gastrointestinal disorders Constipation	35.7% 5/14 • Number of events 5 • From day 1 until 30 days following last dose of infigratinib or until surgery, whichever occurs last, up to a total of 3 months.
Gastrointestinal disorders Disgeusia	35.7% 5/14 • Number of events 5 • From day 1 until 30 days following last dose of infigratinib or until surgery, whichever occurs last, up to a total of 3 months.
Metabolism and nutrition disorders Anorexia	21.4% 3/14 • Number of events 3 • From day 1 until 30 days following last dose of infigratinib or until surgery, whichever occurs last, up to a total of 3 months.
Skin and subcutaneous tissue disorders Dry Mouth	21.4% 3/14 • Number of events 3 • From day 1 until 30 days following last dose of infigratinib or until surgery, whichever occurs last, up to a total of 3 months.
Gastrointestinal disorders Nausea	7.1% 1/14 • Number of events 1 • From day 1 until 30 days following last dose of infigratinib or until surgery, whichever occurs last, up to a total of 3 months.
Skin and subcutaneous tissue disorders Stomatitis/Sore throat	7.1% 1/14 • Number of events 1 • From day 1 until 30 days following last dose of infigratinib or until surgery, whichever occurs last, up to a total of 3 months.
Skin and subcutaneous tissue disorders Xerostomy	7.1% 1/14 • Number of events 1 • From day 1 until 30 days following last dose of infigratinib or until surgery, whichever occurs last, up to a total of 3 months.
Skin and subcutaneous tissue disorders Dry Eyes	21.4% 3/14 • Number of events 3 • From day 1 until 30 days following last dose of infigratinib or until surgery, whichever occurs last, up to a total of 3 months.
Skin and subcutaneous tissue disorders Blurred Vision	7.1% 1/14 • Number of events 1 • From day 1 until 30 days following last dose of infigratinib or until surgery, whichever occurs last, up to a total of 3 months.
Skin and subcutaneous tissue disorders Eye Pain	7.1% 1/14 • Number of events 1 • From day 1 until 30 days following last dose of infigratinib or until surgery, whichever occurs last, up to a total of 3 months.
Skin and subcutaneous tissue disorders Pingueculitis	7.1% 1/14 • Number of events 1 • From day 1 until 30 days following last dose of infigratinib or until surgery, whichever occurs last, up to a total of 3 months.
Skin and subcutaneous tissue disorders Sub-retinal Fluid	7.1% 1/14 • Number of events 1 • From day 1 until 30 days following last dose of infigratinib or until surgery, whichever occurs last, up to a total of 3 months.
Skin and subcutaneous tissue disorders Alopecia	21.4% 3/14 • Number of events 3 • From day 1 until 30 days following last dose of infigratinib or until surgery, whichever occurs last, up to a total of 3 months.
Skin and subcutaneous tissue disorders Nail Infection	21.4% 3/14 • Number of events 3 • From day 1 until 30 days following last dose of infigratinib or until surgery, whichever occurs last, up to a total of 3 months.
Skin and subcutaneous tissue disorders Skin Rash	7.1% 1/14 • Number of events 1 • From day 1 until 30 days following last dose of infigratinib or until surgery, whichever occurs last, up to a total of 3 months.
Respiratory, thoracic and mediastinal disorders Palmar-Plantar Erythrodysesthesia	21.4% 3/14 • Number of events 3 • From day 1 until 30 days following last dose of infigratinib or until surgery, whichever occurs last, up to a total of 3 months.
Investigations Fatigue	28.6% 4/14 • Number of events 4 • From day 1 until 30 days following last dose of infigratinib or until surgery, whichever occurs last, up to a total of 3 months.
Musculoskeletal and connective tissue disorders Jaw Pain	7.1% 1/14 • Number of events 1 • From day 1 until 30 days following last dose of infigratinib or until surgery, whichever occurs last, up to a total of 3 months.
Musculoskeletal and connective tissue disorders Flank Pain	7.1% 1/14 • Number of events 1 • From day 1 until 30 days following last dose of infigratinib or until surgery, whichever occurs last, up to a total of 3 months.
General disorders Headache	7.1% 1/14 • Number of events 1 • From day 1 until 30 days following last dose of infigratinib or until surgery, whichever occurs last, up to a total of 3 months.
Skin and subcutaneous tissue disorders Epistaxis	21.4% 3/14 • Number of events 3 • From day 1 until 30 days following last dose of infigratinib or until surgery, whichever occurs last, up to a total of 3 months.
Renal and urinary disorders Hematuria	7.1% 1/14 • Number of events 1 • From day 1 until 30 days following last dose of infigratinib or until surgery, whichever occurs last, up to a total of 3 months.
General disorders Lightheadedness	7.1% 1/14 • Number of events 1 • From day 1 until 30 days following last dose of infigratinib or until surgery, whichever occurs last, up to a total of 3 months.
Blood and lymphatic system disorders Lower Leg Edema	7.1% 1/14 • Number of events 1 • From day 1 until 30 days following last dose of infigratinib or until surgery, whichever occurs last, up to a total of 3 months.

Additional Information

Mehrad Adibi, MD

M D Anderson Cancer Center

Phone: 713-563-7458

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place