Infigratinib Before Surgery for the Treatment of Upper Tract Urothelial Cancer

NCT04228042 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: 2019-0557NCI-2019-08197
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Renal Pelvis and Ureter Urothelial Carcinoma

Outcome Measures

Primary Outcomes (1)

• Safety and Tolerability - TOX Rate

  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)

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

Secondary Outcomes (2)

• Evaluate the Objective Response Rate (CR+PR) of Infigratinib After 2 Cycles in UTUC With and Without FGFR3alterations

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

• To Evaluate Patient-reported Quality of Life (QOL)

  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

Study Arms (1)

Treatment (infigratinib, surgery)

EXPERIMENTAL

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.

Drug: Infigratinib; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Procedure: Surgical Procedure

Interventions

Infigratinib DRUG

Given PO

Also known as: 3-(2,6-Dichloro-3,5-dimethoxyphenyl)-1-(6-((4-(4-ethylpiperazin-1-yl)phenyl)amino)pyrimidin-4-yl)-1-methylurea, BGJ-398, BGJ398

Treatment (infigratinib, surgery)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Treatment (infigratinib, surgery)

Questionnaire Administration OTHER

Ancillary studies

Treatment (infigratinib, surgery)

Surgical Procedure PROCEDURE

Undergo surgery

Also known as: Operation, Surgery, Surgical, Surgical Intervention, Surgical Interventions, Surgical Procedures, Type of Surgery

Treatment (infigratinib, surgery)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MD Anderson Cancer Center

MeSH Terms

Interventions

infigratinib; Surgical Procedures, Operative

Results Point of Contact

• Title: Mehrad Adibi, MD
• Organization: M D Anderson Cancer Center

mllozano@mdanderson.org

713-563-7458

Study Officials

• Mehrad Adibi, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 30, 2019
• First Posted: January 14, 2020
• Study Start: July 28, 2020
• Primary Completion: April 17, 2024
• Study Completion: April 17, 2024
• Last Updated: January 1, 2025
• Results First Posted: January 1, 2025

Record last verified: 2024-09

Locations

US (1)