Neoplasms

All Conditions

Rare Diseases

Carcinoma

Carcinoma, Transitional Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Transitional Cell Carcinoma

Antineoplastic Agents

All Drugs and Chemicals

Gemcitabine

Cisplatin

Surgeons: the operation shall be performed by senior urologic surgeons. Try to achieve the consistency of operation quality.

Operation: Radical nephroureterectomy (RNU) with an ipsilateral bladder cuff or distal ureterectomy.

Experimental: Neoadjuvant chemotherapy group

Neoadjuvant chemotherapy(Gemcitabine and Cisplatin):

Gemcitabine, 1250mg/m2, d1 d8, Cisplatin, 75mg/m2, d1-d3, 21d, 2-4 cycles.

Surgery:

2-3weeks after Neoadjuvant chemotherapy

Surgeons: the operation shall be performed by senior urologic surgeons. Try to achieve the consistency of operation quality.

Operation: Radical nephroureterectomy (RNU) with an ipsilateral bladder cuff or distal ureterectomy.

Radical nephroureterectomy (RNU) with an ipsilateral bladder cuff

Radical nephroureterectomy

Distal ureterectomy

Gemcitabine, 1250mg/m2, d1 d8, Cisplatin, 75mg/m2, d1-d3, 21d, 2-4 cycles.

Neoadjuvant Chemotherapy

Long Wang, M.D. Ph.D.

The purpose of this study is to see if getting chemotherapy with Gemcitabine and Cisplatin (GC) for 2-4 cycles can help shrink the tumor before undergoing surgery and improves the overall survival for high-grade upper tract urothelial carcinoma.

The purpose of this study is to see if getting chemotherapy with Gemcitabine and Cisplatin (Gemcitabine, 1250mg/m2, d1 d8, Cisplatin, 75mg/m2, d1-d3, 21d, 2-4 cycles) for 2-4 cycles can help shrink the tumor before undergoing surgery and improves the overall survival for high-grade upper tract urothelial carcinoma.

Neoadjuvant Chemotherapy Versus Surgery Alone in Patients With High-Grade UTUC

Neoadjuvant Chemotherapy Versus Surgery Alone in Patients With High-Grade Upper Tract Urothelial Carcinoma

ORR is defined as the percentage of subjects with evidence of a confirmed complete response (CR) or partial response (PR) as per Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1

Number of participants with chemotherapy-related adverse events as assessed by National Cancer Institute Common Toxicity Criteria version 4.0.

Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

Central South University

The Third Xiangya Hospital of Central South University

Hunan Cancer Hospital

Hunan Provincial People's Hospital

Xiangya Hospital of Central South University

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Urinary Bladder Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Urinary Bladder Diseases

Urologic Diseases

Male Urogenital Diseases

Mitogens

Infigratinib

Participants will be randomly assigned (1:1) to receive oral infigratinib administered once daily for the first 3 weeks (21 days) of each 28-day cycle for a maximum of 52 weeks

Participants will be randomly assigned (1:1) to receive oral placebo administered once daily for the first 3 weeks (21 days) of each 28-day cycle for a maximum of 52 weeks

Participants randomly assigned to infigratinib will receive hard gelatin capsules for oral administration of infigratinib 125 mg once a day (administered as one 100-mg capsule and one 25-mg capsule) using a 3 weeks on (Days 1-21) /1 week off (Days 22-28) dosing schedule.

Participants randomly assigned to placebo will receive placebo matching in appearance the investigational product (infigratinib), which will be provided as hard gelatin capsules for oral use and will be administered once daily on a 3 weeks on (Days 1-21) /1 week off (Days 22-28) dosing schedule.

Placebo

David van Veenhuyzen, M.B., Ch.B., M.Pharm.Med.

This is a Phase 3 multicenter, double-blind, randomized, placebo-controlled study to evaluate the efficacy of infigratinib (an oral targeted FGFR1-3 inhibitor) versus placebo, as adjuvant treatment following surgery in adult subjects with invasive urothelial carcinoma and susceptible FGFR3 genetic alterations (mutations, and gene fusions or rearrangements) who have disease that is considered at high risk for recurrence with surgery alone. The study enrolls subjects with either bladder cancer post radical cystectomy or upper tract urothelial cancer post distal ureterectomy and/or nephrectomy. Study treatment is randomized 1:1 between infigratinib or placebo with treatment up to 1 year or until invasive local, distal, or metastatic disease recurrence confirmed by independent imaging reviewer.

Participants will be randomly assigned (1:1) to receive oral infigratinib phosphate or placebo

As a double-blind study, participants, investigators, study monitor(s) and the clinical study team will be blinded to the treatment administered.

Oral Infigratinib for the Adjuvant Treatment of Subjects With Invasive Urothelial Carcinoma With Susceptible FGFR3 Genetic Alterations

Phase 3, Multicenter, Double-Blind, Randomized, Placebo-Controlled Trial of Infigratinib for the Adjuvant Treatment of Subjects With Invasive Urothelial Carcinoma With Susceptible FGFR3 Genetic Alterations (PROOF 302)

DFS was defined as the number of months from date of randomization to local/regional invasive or metastatic recurrence or death due to any cause (referred as DFS event), whichever occurs earlier.

Due to early termination of the study by the sponsor, results will focus primarily on the primary and key secondary endpoints of the study. Due to early termination of the study by the sponsor, data were censored for 85.0% to 89.5% of all subjects. Data cutoff 28 Feb 2023.

DFS was defined as the number of months from date of randomization to local/regional invasive or metastatic recurrence or death due to any cause (referred as DFS event), whichever occurs earlier. Due to early termination of the study by the sponsor, data were censored for 85.0% to 89.5% of all subjects. Data cutoff 28 Feb 2023.

MFS was defined as the time from randomization to any metastatic recurrence as determined by the investigator, or death due to any cause, whichever occurred earlier. Due to early termination of the study by the sponsor, data were censored for 85.0% to 89.5% of all subjects. Data cutoff 28 Feb 2023.

Overall survival time was defined as the number of months from randomization to death. Due to early termination of the study by the sponsor, data were censored for 85.0% to 89.5% of all subjects. Data cutoff 28 Feb 2023.

Investigator assessment of intraluminal low-risk recurrence as assessed by DFS. Due to early termination of the study by the sponsor, data were censored for 85.0% to 89.5% of all subjects. Data cutoff 28 Feb 2023.

Helsinn Healthcare SA

QED Therapeutics, Inc.

AEs were assessed by the investigator according to the CTCAE version 5.0 and coded using MedDRA version 23.1.

Treatment-emergent AEs are reported and include all AEs with onset after the first administration of study treatment and up to last administration of study treatment + 30 days if subjects ended study treatment. For a subject who had not ended study treatment, all the AEs after the first administration of study drug were considered treatment-emergent.

Infigratinib 125 mg once daily (3 weeks on / 1 week off treatment)

Infigratinib 125 mg

Placebo once daily (3 weeks on / 1 week off treatment)

125 mg oral infigratinib once daily for the first 3 weeks (21 days) of each 28-day cycle

Placebo once daily for the first 3 weeks (21 days) of a 28-day treatment cycle

Total

Age Group

Age, Categorical

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

North America

Europe

North America includes United States and Canada; Europe includes Germany, Spain, France, Italy, Netherlands, and Belgium

Region of Enrollment

Functional status was assessed at baseline using the Eastern Cooperative Oncology Group Performance Scale (ECOG PS), defined as follows:

0. Fully active, able to carry out all pre-disease performance without restriction.

1. Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature.
2. Ambulatory and capable of all selfcare but unable to carry out any work activities; up and about more than 50% of waking hours.
3. Capable of only limited selfcare; confined to bed or chair more than 50% of waking hours.
4. Completely disabled.

ECOG PS

Primary Site of Cancer

Histological Subtype

Tumor (T). T1, T2, T3, T4: Refers to the size and/or extent of the main tumor. The higher the number after the T, the larger the tumor or the more it has grown into nearby tissues.

Screening Diagnosis Category (Pathologic Stage at Definitive Surgery) - Tumor (T)

Node (N) refers to the number of nearby lymph nodes that have cancer. NX: Cancer in nearby lymph nodes cannot be measured; N0: There is no cancer in nearby lymph nodes; N1, N2, N3: Refers to the number and location of lymph nodes that contain cancer. The higher the number after the N, the more lymph nodes that contain cancer.

Screening Diagnosis Category (Pathologic Stage at Definitive Surgery) - Node (N)

Time from Initial Diagnosis to Randomization (Days)

Type of FGFR3 Alteration (Local)

FGFR3 Mutation Result (Local)

FGFR3 Fusion Result (Local)

Type FGFR3 Alteration (Central)

FGFR3 Mutation Result (Central)

FGFR3 Fusion Result (Central)

Tumor Mutational Burden

Acting Chief Medical Officer

Intent-to-treat (ITT) population, which included all subjects who were randomized

Centrally Determined Disease-free Survival (DFS)

ITT population includes all subjects who were randomized

Investigator-assessed DFS

Metastasis-free Survival (MFS)

Overall Survival (OS)

Investigator-reviewed DFS Including Intraluminal Low-Risk Recurrence

Number of Participants With Adverse Events (AEs)

Number of Participants With Serious Adverse Events (SAEs)

Participants were randomly assigned (1:1) to receive oral infigratinib administered once daily for the first 3 weeks (21 days) of each 28-day cycle for a maximum of 52 weeks.

Infigratinib: Participants randomly assigned to infigratinib received hard gelatin capsules for oral administration of infigratinib 125 mg once a day (administered as one 100-mg capsule and one 25-mg capsule) using a 3 weeks on (Days 1-21) /1 week off (Days 22-28) dosing schedule.

Participants were randomly assigned (1:1) to receive oral placebo administered once daily for the first 3 weeks (21 days) of each 28-day cycle for a maximum of 52 weeks.

Placebo: Participants randomly assigned to placebo received placebo matching in appearance the investigational product (infigratinib) provided as hard gelatin capsules for oral use and administered once daily on a 3 weeks on (Days 1-21) /1 week off (Days 22-28) dosing schedule.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Neoadjuvant Chemotherapy Versus Surgery Alone in Patients With High-Grade UTUC	NCT02876861	High-Grade Uppe...	Radical nephrou... Distal ureterec... Neoadjuvant Che...	18 Years - 80 Years	Xiangya Hospital of Central South University
Neoadjuvant Chemotherapy Versus Surgery Alone in Patients With High-Grade UTUC	NCT02876861	High-Grade Uppe...	Radical nephrou... Distal ureterec... Neoadjuvant Che...	18 Years - 80 Years	Xiangya Hospital of Central South University
Oral Infigratinib for the Adjuvant Treatment of Subjects With Invasive Urothelial Carcinoma With Susceptible FGFR3 Genetic Alterations	NCT04197986	Upper Tract Uro... Urothelial Blad...	Infigratinib Placebo	18 Years -	QED Therapeutics, Inc.
Oral Infigratinib for the Adjuvant Treatment of Subjects With Invasive Urothelial Carcinoma With Susceptible FGFR3 Genetic Alterations	NCT04197986	Upper Tract Uro... Urothelial Blad...	Infigratinib Placebo	18 Years -	QED Therapeutics, Inc.

Spots Global Cancer Trial Database for distal ureterectomy