| CTRI Number |
CTRI/2021/11/038016 [Registered on: 12/11/2021] Trial Registered Prospectively |
| Last Modified On: |
06/10/2023 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Single Arm Study |
|
Public Title of Study
|
An Efficacy and Safety Study of Erdafitinib (JNJ42756493) in Participants with Urothelial Cancer |
|
Scientific Title of Study
|
A Phase 2, Two-arm Multicenter, Open-Label Study to Determine the Efficacy and the Safety of Two Different Dose Regimens of a pan-FGFR Tyrosine Kinase Inhibitor JNJ-42756493 in Subjects with Metastatic or Surgically Unresectable Urothelial Cancer with FGFR Genomic Alterations
|
| Trial Acronym |
DDI Sub study |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| NIL |
NIL |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Sanish Davis |
| Designation |
R and D, Director, GCO India |
| Affiliation |
Johnson and Johnson Pvt. Ltd. |
| Address |
Arena Space, Behind Majas Bus Depot, Off. J. V. Link Road, Jogeshwari (E).
Mumbai
MAHARASHTRA
400060
India |
| Phone |
|
| Fax |
|
| Email |
sdavis20@its.jnj.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Sanish Davis |
| Designation |
R and D, Director, GCO India |
| Affiliation |
Johnson and Johnson Pvt. Ltd. |
| Address |
Arena Space, Behind Majas Bus Depot, Off. J. V. Link Road, Jogeshwari (E).
Mumbai (Suburban)
MAHARASHTRA
400060
India |
| Phone |
9820958943 |
| Fax |
|
| Email |
sdavis20@its.jnj.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr Sanish Davis |
| Designation |
R and D, Director, GCO India |
| Affiliation |
Johnson and Johnson Pvt. Ltd. |
| Address |
Arena Space, Behind Majas Bus Depot, Off. J. V. Link Road, Jogeshwari (E).
Mumbai (Suburban)
MAHARASHTRA
400060
India |
| Phone |
9820958943 |
| Fax |
|
| Email |
sdavis20@its.jnj.com |
|
|
Source of Monetary or Material Support
|
| Janssen Research & Development , LLC |
|
|
Primary Sponsor
|
| Name |
Janssen Research Development LLC |
| Address |
Johnson and Johnson Pvt. Ltd., 501 Arena space, Behind Majas Bus Depot, off J.V. Link Road, Jogeshwari East, Mumbai400060 Maharashtra |
| Type of Sponsor |
Pharmaceutical industry-Global |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
Belgium
France
Spain
United States of America
India |
|
Sites of Study
|
| No of Sites = 4 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Nirmal Raut |
BHAKTIVEDANTA HOSPITAL & RESEARCH INSTITUTE |
Bhaktivedanta Swami marg, opp Iskcon temple, Srishti Complex sector 1, Mira Road (East), Maharashtra, 401107, India
Thane
MAHARASHTRA |
9930398156
drnirmalraut@gmail.com |
| Dr Govind Babu |
Health Care Global Enterprises pvt Ltd |
9/1, P. Kalingarao Road, Sampangi Rama Nagar, HCG Tower 4, 2 Floor, Bangalore, Karnataka, 560027, India
Bangalore
KARNATAKA |
9845072940
kgblaugh@gmail.com |
| Dr Mahesh Desai |
Muljibhai Patel Urological Hospital |
Dr Vijendra Desai Road, Ground Floor, Main Building, Nadiad, Guajarat, 387001, India
Surat
GUJARAT |
9824028041
mrdesai@mpuh.org |
| Dr Gaurav Aggarwal |
Tata Medical Center |
14 MAR (E-W), Rajarhat, New Town, 1st floor, Academics and Research Building, Kolkata, West Bengal, 700160, India
Kolkata
WEST BENGAL |
7873947779
gaurav.aggarwal@tmckolkata.com |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 4 |
| Name of Committee |
Approval Status |
| Muljibhai Patel Society for research in Nephro Urology Ethics Committee |
Approved |
| Bhaktivedanta Hospital Ethics Committee |
Approved |
| HCG-Central Ethics Committee |
Approved |
| Institutional Review Board Tata Medical Center |
Submittted/Under Review |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: N33||Bladder disorders in diseases classified elsewhere, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
Erdafitinib |
8 mg orally once daily for 28 days on a 28 day cycle.
|
| Intervention |
Metformin |
DDI substudy will receive pretreatment with single dose of metformin 1000mg on Day -1 and single dose of metformin on Day 14. |
| Intervention |
Midazolam |
DDI substudy will receive pretreatment with single dose of midazolam 2.5mg oral solution on Day -2 and single dose of midazolam on Day 13. |
| Comparator Agent |
NA |
NA |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
65.00 Year(s) |
| Gender |
Both |
| Details |
- Must have histologic demonstration of metastatic
or surgically unresectable urothelial cancer. Minor components of variant histology such as glandular or squamous differentiation, or evolution to more aggressive phenotypes such as sarcomatoid or micropapillary change are acceptable
- Must have measurable disease according to the
Response Evaluation Criteria in Solid Tumors
(RECIST, version 1.1) at baseline
- Must have an Eastern Cooperative Oncology Group
(ECOG) performance status score 0, 1, or 2
- Must have adequate bone marrow, liver, and renal function as described in protocol
- Negative pregnancy test (urine or serum beta human chorionic gonadotropin [b-hCG]) at Screening for women of child bearing potential who are sexually active
- Must have shown disease progression according to RECIST, version 1.1, following prior chemotherapy for metastatic or surgically unresectable urothelial cancer.
Participants who received neoadjuvant or adjuvant
chemotherapy and showed disease recurrence or
progression according to RECIST, version 1.1, within 12 months of the last dose are considered to have received chemotherapy in the metastatic setting. These participants will be referred to as chemo-refractory participants. (Participants who have shown disease progression according to RECIST, version 1.1 following prior treatment with anti-Programmed death-ligand 1 (anti PDL1/PD1) antibodies are also eligible)
For DDI substudy
- Disease progression following prior chemotherapy for metastatic or surgically unresectable urothelial cancer. Participants who received neoadjuvant or adjuvant chemotherapy and showed disease recurrence or progression within 12 months of the last dose are considered to have received chemotherapy in the metastatic setting. |
|
| ExclusionCriteria |
| Details |
- Received chemotherapy, targeted therapies, definitive radiotherapy, or treatment with an investigational anticancer agent within 2 weeks (in the case of nitrosoureas and mitomycin C, within 6 weeks; in the case of immunotherapy, within 4 weeks) before the first administration of study drug. Localized palliative radiation therapy (but should not include radiation to target lesions) and ongoing bisphosphonates and denosumab, are
permitted
- Has persistent phosphate level greater than upper limit of normal (ULN) during screening (within 14 days of treatment and prior to Cycle 1 Day 1) and despite
medical management
- Has a history of or current uncontrolled cardiovascular disease
- Females who are pregnant, breast-feeding, or
planning to become pregnant within 3 months after
the last dose of study drug and males who plan to
father a child while enrolled in this study or within 5 months after the last dose of study drug
- Has not recovered from reversible toxicity of prior anticancer therapy (except toxicities which are not clinically significant such as alopecia, skin
discoloration, or Grade 1 neuropathy) |
|
|
Method of Generating Random Sequence
|
Not Applicable |
|
Method of Concealment
|
Not Applicable |
|
Blinding/Masking
|
Open Label |
|
Primary Outcome
|
| Outcome |
TimePoints |
| Plasma Concentration of Midazolam and its Metabolite (1-OH midazolam) |
Plasma Concentration of Midazolam and its Metabolite (1-OH midazolam) at Day-2 and Day 15 |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
| None |
None |
|
|
Target Sample Size
|
Total Sample Size="22"
Sample Size from India="10"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
Phase 2 |
|
Date of First Enrollment (India)
|
12/01/2022 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
28/04/2015 |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="1"
Months="7"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Closed to Recruitment of Participants |
| Recruitment Status of Trial (India) |
Closed to Recruitment of Participants |
|
Publication Details
|
|
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
Brief Summary
Modification(s)
|
The purpose of this study is to evaluate the objective response rate (complete response [CR]+ partial response [PR]) of the selected dose regimen in participants with metastatic or surgically unresectable urothelial cancers that harbor specific FGFR genomic alterations. This is a multicenter, open-label study (participants will know the identity of study drugs administered) to evaluate the efficacy and safety of erdafitinib in participants with urothelial cancer. The study comprises a 30-days Screening Phase, a Treatment Phase comprised of 28-day treatment cycles that will continue until disease progression or unacceptable toxicity occurs, and a post treatment Follow-up Phase that will extend from the End of-Treatment Visit until the participant has died, withdraws consent, is lost to follow-up, or the end of the study, whichever comes first. The end of study is defined as the date when all participants have completed the study treatment (Regimens 1 to 3) or until the last participant enrolled under the drug-drug interaction (DDI) substudy completes the end of treatment visit,(whichever happens last). The purpose of DDI sub-study is to evaluate the interaction of repeated doses of erdafitinib with a sensitive cytochrome 450 (CYP) 3A substrate (midazolam) and with an organic cation transporter 2 (OCT2) probe substrate (metformin). Safety will be monitored throughout the study. |