Infigratinib Before Surgery for the Treatment of Upper Tract Urothelial Cancer

  • days left to enroll
  • participants needed
  • sponsor
    M.D. Anderson Cancer Center
Updated on 26 January 2021


This phase Ib trial studies the side effects of infigratinib before surgery in treating patients with upper tract urothelial cancer. Infigratinib may stop the growth of tumor cells by blocking the activities of a gene called FGFR needed for cell growth. Giving infigratinib before surgery may cause the tumor to shrink, which may make the surgical procedure easier and/or reduce the need for more extensive surgery.



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.

Condition Renal Pelvis and Ureter Urothelial Carcinoma, urothelial carcinoma of the upper urinary tract
Treatment surgical procedure, questionnaire administration, quality-of-life assessment, Infigratinib
Clinical Study IdentifierNCT04228042
SponsorM.D. Anderson Cancer Center
Last Modified on26 January 2021


Yes No Not Sure

Inclusion Criteria

Have low grade UTUC undergoing nephroureterectomy or ureterectomy, or high grade UTUC and not eligible for cis-platin neoadjuvant chemotherapy either due to medical comorbidities (e.g., cardiac dysfunction, hearing loss, glomerular filtration rate [GFR] < 50), or based on < 49% risk prediction of non-organ confined disease by clinical nomogram
Have adequate biopsy tissue available for mutational analysis, as determined by the study pathologist, prior to enrollment. Any biopsy of index UTUC tissue available within 6 weeks of enrollment may be used
Calculated or measured creatinine clearance >= 30 mL/min
Have an Eastern Cooperative Oncology Group (ECOG) performance status =< 2
Are able to read and/or understand the details of the study and provide written evidence of informed consent as approved by Institutional Review Board (IRB)/Independent Ethics Committee (IEC)
Have recovered from AEs of previous systemic anti-cancer therapies to baseline or grade 1, except for alopecia
Are able to swallow and retain oral medication
Are willing and able to comply with scheduled visits, treatment plan and laboratory tests
If a woman of childbearing potential (WOCBP), must have a negative pregnancy test within 7 days of the first dose of study drug. A woman is not of childbearing potential if she has undergone surgical sterilization (total hysterectomy, or bilateral tubal ligation or bilateral oophorectomy at least 6 weeks before taking study drug) or if she is post-menopausal and has had no menstrual bleeding of any kind including menstrual period, irregular bleeding, spotting, etc., for at least 12 months, with an appropriate clinical profile, and there is no other cause of amenorrhea (e.g., hormonal therapy, prior chemotherapy). WOCBP and males whose sexual partners are WOCBP must agree to use barrier contraception and a second form of highly effective contraception (Clinical Trials Facilitation Group, 2014) while receiving study drug and for 3 months following their last dose of study drug. Alternatively, total abstinence is also considered a highly effective contraception method when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. Sexually active males must use a condom during intercourse while taking drug and for 3 months after the last dose of the study drug and should not father a child during this period. A condom is required to be used also by vasectomized men as well as during intercourse with a male partner to prevent delivery of the drug via seminal fluid

Exclusion Criteria

Have a history of another primary malignancy within 3 years except
Adequately treated in situ carcinoma of the cervix, non-melanoma carcinoma of the skin
Any other untreated cancer deemed by treating physician to be at low risk for progression during the study period (such as low or intermediate risk prostate cancer)
Curatively treated malignancy that is not expected to have recurrence or require treatment during the course of the study
Have uncontrolled bladder cancer. Patients with bladder cancer must have bladder cleared of disease by transurethral resection prior to initiating treatment and must not be at need for systemic therapy
Have any other medical condition that would, in the investigator's judgment, prevent the subject's participation in the clinical study due to safety concerns or compliance with clinical study procedures
Have current evidence of corneal or retinal disorder/keratopathy including, but not limited to, bullous/band keratopathy, corneal abrasion, inflammation/ulceration, keratoconjunctivitis, confirmed by ophthalmologic examination. Subjects with asymptomatic ophthalmologic conditions assessed by the investigator to pose minimal risk for study participation may be enrolled in the study
Have a history and/or current evidence of extensive tissue calcification including, but not limited to, the soft tissue, kidneys, intestine, myocardium, vasculature and lung with the exception of calcified lymph nodes, minor pulmonary parenchymal calcifications, and asymptomatic coronary calcification
Have impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral infigratinib (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection)
Have current evidence of endocrine alterations of calcium/phosphate homeostasis, e.g., parathyroid disorders, history of parathyroidectomy, tumor lysis, tumoral calcinosis etc
Are currently receiving treatment with agents that are known strong inducers or inhibitors of CYP3A4 and medications which increase serum phosphorus and/or calcium concentration. Subjects are not permitted to receive enzyme-inducing anti-epileptic drugs, including carbamazepine, phenytoin, phenobarbital, and primidone
Have consumed grapefruit, grapefruit juice, grapefruit hybrids, pomegranates, star fruits, pomelos, Seville oranges or products containing juice of these fruits within 7 days prior to first dose of study drug
Have used medications known to prolong the QT interval and/or are associated with a risk of torsades de pointes (TdP) 7 days prior to first dose of study drug
Have used amiodarone within 90 days prior to first dose of study drug
Are currently using therapeutic doses of warfarin sodium or any other coumadin-derivative anticoagulants or using direct thrombin inhibitors (e.g., argatroban) or factor Xa inhibitors (e.g., rivaroxaban) that are primarily metabolized by CYP3A4. Heparin and/or low molecular weight heparins or direct thrombin inhibitors and/or factor Xa inhibitors that are not metabolized by CYP3A4 (e.g., dabigatran, edoxaban) are allowed
Absolute neutrophil count (ANC) < 1,000/mm^3 (1.0 x 10^9/L)
Platelets < 100,000/mm^3 (75 x 10^9/L)
Hemoglobin < 9.0 g/dL
Total bilirubin > 1.5 x upper limit of normal (ULN) (unless documented Gilbert's syndrome)
Aspartate aminotransferase (AST)/ serum glutamic-oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/ serum glutamic-pyruvic transaminase (SGPT) > 2.5 x ULN (AST and ALT > 5 x ULN in the presence of liver involvement of cholangiocarcinoma)
Calculated or measured creatinine clearance of < 30 mL/min
Have amylase or lipase > 2.0 x ULN
Have abnormal calcium-phosphate homeostasis
Inorganic phosphorus outside of local normal limits
Total corrected serum calcium outside of local normal limits
Have clinically significant cardiac disease including any of the following
Congestive heart failure requiring treatment (New York Heart Association grade >= 2), left ventricular ejection fraction (LVEF) < 50% or local lower limit of normal as determined by echocardiogram (ECHO), or uncontrolled hypertension
Presence of Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0 or later grade >= 2 ventricular arrhythmias, atrial fibrillation, bradycardia, or conduction abnormality
Unstable angina pectoris or acute myocardial infarction =< 3 months prior to first dose of study drug
Corrected QT interval by Fridericia (QTcF) > 470 msec (males and females)
Note: If the QTcF is > 470 msec in the first electrocardiography (ECG), a total of 3 ECGs separated by at least 5 minutes should be performed. If the average of these 3 consecutive results for QTcF is =< 470 msec, the subject meets eligibility in this regard
Known history of congenital long QT syndrome
Have had a recent (=< 3 months) transient ischemic attack or stroke
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact



Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider


Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 



Reply by • Private

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note