Plain English Summary
Background and study aims
The primary purpose of this clinical trial is to evaluate the safety and efficacy of erdafitinib (ERDA; a fibroblast growth factor receptor (FGFR)- inhibitor) alone or in combination with cetrelimab (CET; an anti-PD-1 monoclonal antibody) as neoadjuvant treatment in cisplatin-ineligible patients with muscle-invasive bladder cancer (MIBC) whose tumours express FGFR gene alterations. ERDA is an experimental drug in this clinical trial and is being studied as a potential new treatment in the neoadjuvant setting of patients with non-MIBC which carry specific alterations in the FGFR family. CET is an anti-PD-1 monoclonal antibody (an immune checkpoint inhibitor (ICI)) being studied in the treatment of several tumours, including bladder cancer. A combination of CET plus ERDA seems an interesting approach in FGFR-mutated bladder cancer due to different mechanisms of action and non-overlapping toxicities, as shown in a phase II study in metastatic UC. The SOGUG Group (Sponsor) is a non-profit scientific association whose aim is to promote and develop specific programmes of study and research in the field of genito-urinary tumours.
Who can participate?
Patients aged over 18 years old with metastatic bladder cancer
What does the study involve?
The number of patients planned in this study is 90, with 45 in each cohort. There will be 21 study centres in 4 countries that will participate in the main study. Treatment will be assigned through a centralized allocation by order of arrival.
In the ERDA group, the patient will receive ERDA 8 mg (two 4mg tablets) orally daily for 9 or 12 weeks (3 or 4 cycles of 3 weeks each). In ERDA plus CET combination group, patients will receive ERDA 8 mg (two 4 mg tablets) orally daily, in combination with CET 360 mg intravenously on Cycle 1 Day 1, then every 3 weeks (21 days), for 9 or 12 weeks (3 or 4 cycles of 3 weeks each).
When the treatment period ends, the patient will have an end-of-trial visit and an imaging and laboratory test before proceeding to surgery. The overall study duration is 60 months.
What are the possible benefits and risks of participating?
To protect the patient’s safety, the study doctor will evaluate medical records, and perform physical examinations and laboratory studies to decide if the patient can participate in the clinical trial. As with all medicines, the drugs that will be used in this study may cause side effects, although not everyone will experience them. During the study, patients will be carefully monitored to detect the possible onset of these effects.
The most common side effects of each drug used in this study are indicated below. These side effects may or may not be more intense when the drugs are administered jointly. These are the risks and side effects that could be related to each drug:
1. Erdafitinib: Very Common (occurring in ≥10% of patients)
Higher than normal levels of phosphate in the blood; dryness of the mouth; ulcers, blisters or pain in the mouth including cheeks, tongue, or lips; diarrhoea; nail changes and disorders, including the nails, separation from the nail bed, nail pain, nail bleeding, breaking of the nails, colour or texture changes in your nails; skin problems including dryness and cracking; skin reactions with peeling, redness, swelling tingling or pain in palms of the hands and soles of the feet, called hand-foot syndrome; dryness of eyes; redness and irritation of the eye, may be associated with increased tearing of the eyes, itchy eyes, inflamed eyes; loss of hair; decreased appetite; taste disorder with food tasting sour, bitter or metallic.
Common: (occurring in ≥ 1% to < 10% of subjects)
Eye disorders pertaining to fluid build-up under the retina (the light-sensitive layer at the back of the eye) that may or may not be associated with visual symptoms such as blurred or diminished vision or loss of vision; infected skin around the nail; itching; dryness of the nose.
Less Common (occurring in < 1% subjects); A condition caused by calcium deposits in blood vessels, that can lead to painful red skin lesions, that may sometimes lead to open wounds, and the open wounds could become infected; skin lumps that may be skin coloured or white, soft or hard, and can become painful.
2. Cetrelimab:
Very Common (affects more than 1 user in 10):
Physical weakness and loss of strength; feeling tired or weak; shortness of breath; cough; diarrhoea (watery, loose, or soft stools); nausea; vomiting; decreased appetite; fever; pain in specific regions such as in the muscles, and bones, back, stomach, or joints; skin rash, dry skin or redness, itching; increase in liver enzymes in the blood; changes in blood levels of electrolytes (such as sodium or potassium), enzymes (such as amylase or lipase) or metabolites (such as creatinine); allergic reaction or reaction to the medicine infusion which may cause fever, chills, rash.
Common (affects 1 to 10 users in 100)
Infrequent bowel movements (constipation); changes in blood pressure (hypertension or hypotension); headache; swelling in extremities (edema); underactive thyroid gland, which can cause tiredness or weight gain, overactive thyroid gland, which can cause rapid heart rate, sweating, weight loss; high sugar levels in the blood (hyperglycemia); difficult sleeping or falling asleep (insomnia); decreased number of platelets or white blood cells; rapid heart rate (tachycardia); urinary tract infection; dizziness; nervous behaviour (anxiety); inflammation of the intestines (gastroenteritis or colitis) or stomach (gastritis) characterized by vomiting, stomach pain, constipation, dry mouth, bloody stools; dry mouth, mouth ulcers and cold sores (stomatitis); change in taste (dysgeusia); difficulty swallowing (dysphagia); indigestion (dyspepsia); blockage of the small or large bowel (intestinal obstruction); changes in weight; infections of the upper respiratory tract including bronchitis; serious lung infection (pneumonia); coughing up blood (haemoptysis); build-up of fluid in the tissues surrounding the lungs, chest cavity or abdomen (pleural effusion or ascites); inflammation of the lungs (pneumonitis), characterized by coughing and difficulty breathing, shortness of breath, chest pain; inflammation of the kidney, kidney failure, blood in urine.
The patient may experience some, none or all of these side effects and they may be mild, moderate or severe. Many of these side effects may disappear when the treatment is discontinued. In addition, there is always a risk of a very rare or previously unknown side effect occurring. The study doctor will inform the patient of any new data that may become available during the course of the study regarding the safety of the treatment.
Where is the study run from?
Spanish Oncology Genitourinary Group (Spain)
When is the study starting and how long is it expected to run for?
February 2023 to December 2027
Who is funding the study?
Spanish Oncology Genitourinary Group (Spain)
Who is the main contact?
trialmanager@sogug.es
Plain English summary under review with external organisation
Study website
Contact information
Type
Scientific
Contact name
Dr Trial Manager
ORCID ID
Contact details
Spanish Oncology Genitourinary Group
Velázquez 7
Madrid
28001
Spain
+34 610 28 69 15
trialmanager@sogug.es
Type
Principal Investigator
Contact name
Prof Syed Hussain
ORCID ID
https://orcid.org/0000-0003-1552-511X
Contact details
Department of Oncology and Metabolism
Room 228
2nd Floor
Broomcross Building
Weston Park Hospital
Whitham Road
Sheffield
S10 2SJ
United Kingdom
+44 (0)1142159682
syed.hussain@sheffield.ac.uk
Type
Public
Contact name
Dr Trial Manager
ORCID ID
Contact details
Spanish Oncology Genitourinary Group
Velázquez 7
Madrid
28001
Spain
+34 610 28 69 15
trialmanager@sogug.es
Additional identifiers
EudraCT/CTIS number
2022-002586-15
IRAS number
1006918
ClinicalTrials.gov number
Nil known
Protocol/serial number
SOGUG-2020-IEC(VEJ)-11, IRAS 1006918, CPMS 55028
Study information
Scientific title
A phase II, open-label, multi-centre, multi-national interventional trial to evaluate the efficacy and safety of erdafitinib (ERDA) monotherapy and ERDA and cetrelimab combination as neoadjuvant treatment in cisplatin-ineligible patients with muscle-invasive bladder cancer whose tumours express FGFR gene alterations
Acronym
SOGUG-NEOWIN TRIAL
Study hypothesis
Primary objectives:
To assess the antitumor activity measured as pT0N0 rate, defined as no evidence of residual disease based on a pathological review of the surgical specimen
To assess the percentage of pathological downstaging response
Secondary objectives:
To evaluate the percentage of tumour downstaging
To estimate the event-free survival (EFS)
To estimate the overall survival (OS)
To evaluate the Objective Response Rate (ORR) after neoadjuvant treatment
To assess the safety profile and tolerability of both schemes
To calculate the rate of delay of surgery
Ethics approval(s)
Approval pending (UK), North West – Greater Manchester Central Research Ethics Committee (3rd Floor Barlow House, 4 Minshull Street, Manchester, M1 3DZ, UK; +44 (0)2071048328; gmcentral.rec@hra.nhs.uk), ref: 23/NW/0081
Study design
Phase II open-label multi-centre multi-national interventional study
Primary study design
Interventional
Secondary study design
Non randomised study
Study setting(s)
Hospital
Study type
Treatment
Patient information sheet
Not available in web format, please use the contact details to request a participant information sheet
Condition
Muscle-invasive bladder cancer
Intervention
Patients will receive 9 or 12 weeks of neoadjuvant (minimum 3 – maximum 4 cycles of 3 weeks each) treatment with erdafitinib alone (cohort 1) or erdafitinib plus cetrelimab (CET; cohort 2) before proceeding to radical cystectomy (RC) (to be performed within 2 - 6 weeks after the end of treatment):
• ERDA (cohort 1): 8 mg (two 4 mg tablets) as a daily flat dose.
• ERDA + CET (cohort 2): ERDA: same as in cohort 1, in combination with CET: 360 mg intravenously (IV) on Cycle 1 Day 1, then every 3 weeks (21 days) thereafter (Q3W).
Intervention type
Drug
Pharmaceutical study type(s)
Phase
Phase II
Drug/device/biological/vaccine name(s)
Erdafitinib, cetrelimab
Primary outcome measure
The following primary endpoints are assessed after a maximum of 30 weeks from the start of treatment (first follow-up visit) on specimens obtained during radical cystectomy:
1. Pathological complete response (pCR), defined as the proportion of patients whose pathological staging was ypT0N0M0, measured using specimens obtained post-radical cystectomy following the study intervention
2. Pathological downstaging <ypT2, referring to patients whose pathological staging following radical cystectomy is ypT0, ypTa, ypTis or ypT1. A local pathological assessment will be done on specimens obtained during radical cystectomy (for coprimary endpoints). Thereafter, during the follow-up period, pathological assessments will be scheduled according to local standards and as clinically indicated.
Secondary outcome measures
The following secondary endpoints are assessed during the treatment and follow-up period:
1. Rate of pathological downstaging (pDS), defined as patients whose pathological staging following radical cystectomy is ypT0, ypTa, ypTis or ypT1.
2. Event-free Survival rate, defined as radiographically confirmed disease progression, death or any event that prevents the performance of radical cystectomy, including initiation of any additional therapy prior to radical cystectomy. Progression will be assessed using computed tomography (CT)/magnetic resonance imaging (MRI) and/or Positron Emission Tomography (PET)-CT (per standard local imaging practices).
3. Overall survival (OS), defined as the proportion of patients who are alive at 1, 2 and 3 years, from the date of study entry until death from any cause. Progression will be assessed using computed tomography (CT)/magnetic resonance imaging (MRI) and/or Positron Emission Tomography (PET)-CT (per standard local imaging practices).
4. Overall response rate (ORR), defined as the percentage of patients with partial or complete response according to RECIST v1.1 criteria. Progression will be assessed using computed tomography (CT)/magnetic resonance imaging (MRI) and/or Positron Emission Tomography (PET)-CT (per standard local imaging practices).
5. Adverse events measured using corresponding technical depend on the adverse event. All the information will be recorded in the medical records.
6. Rate of delay of surgery, classed as a delay event if performed > 6 weeks after the last dose of treatment, measured using the rate of delay of surgery will be taken in days/weeks.
Overall study start date
15/02/2023
Overall study end date
31/12/2027
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Written informed consent stating that he or she understands the purpose of the study and the procedures involved and agrees to participate in the study
2. Histologically confirmed diagnosis of MIBC (Stage T2-4a N0/N1 M0) obtained via a diagnostic or maximal TURBT performed no later than 3 months prior to start the screening visit
3. Pure or predominant (≥50%) UC histology as determined at the local site
4. Age ≥ 18 years
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
6. Decline or ineligible (“unfit”) for cisplatin-based chemotherapy
7. Presence of a selected FGFR alteration on analysis of tumour biopsy
8. Adequate organ function
9. No other malignancy
10. Willingness to avoid pregnancy or fathering children
Participant type(s)
Patient
Age group
Mixed
Lower age limit
18 Years
Sex
Both
Target number of participants
90
Participant exclusion criteria
1. Clinical evidence of N2-N3 tumours or metastatic bladder cancer
2. Has tumour with any neuroendocrine or small cell component
3. Patients who are not considered fit for cystectomy or reject cystectomy
5. Prior FGFR-targeted or antiPD1/PDL1 systemic therapy
6. Prior systemic therapy, radiation therapy, or surgery for bladder cancer
Recruitment start date
04/05/2023
Recruitment end date
30/06/2025
Locations
Countries of recruitment
France, Italy, United Kingdom
Study participating centre
-
-
United Kingdom
Sponsor information
Organisation
Spanish Oncology Genitourinary Group
Sponsor details
C/o: Silvia Martínez Cruz
Velázquez 7
Madrid
28001
Spain
+34 610287201
secretaria@sogug.es
Sponsor type
Research organisation
Website
ROR
Funders
Funder type
Research organisation
Funder name
SOGUG NEOWIN
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
1. Internal report
2. Conference presentation
3. Publication on a website
4. Submission to regulatory authorities
5. A description of this clinical trial will be available on http://www.ClinicalTrials.gov and UK patient registry; and other websites required by European law or Participant's countries. These websites will not include information that can identify patients. At most, the website will include a summary of the results.
Intention to publish date
31/12/2028
Individual participant data (IPD) sharing plan
The data-sharing plans for the current study are unknown and will be made available at a later date
IPD sharing plan summary
Data sharing statement to be made available at a later date
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|