CTRI/2024/10/075224 [Registered on: 14/10/2024] Trial Registered Prospectively
Last Modified On:
11/10/2024
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Randomized, Parallel Group, Active Controlled Trial
Public Title of Study
A study of Repotrectinib versus Crizotinib in Participants with Locally Advanced or Metastatic Tyrosine Kinase Inhibitor ROS1 positive Non-Small Cell Lung Cancer
Scientific Title of Study
Randomized, Open-label, Multicenter,Phase 3 Trial of Repotrectinib VersusCrizotinib in
Participants with Locally Advanced or Metastatic Tyrosine Kinase Inhibitor (TKI)-naïve ROS1-positive Non-Small Cell Lung Cancer (NSCLC) (TRIDENT-3)
Trial Acronym
NIL
Secondary IDs if Any
Secondary ID
Identifier
2023-505604-32-00
EudraCT
CA127-1030, Version No V01,Protocol Date 12 May 2023
Protocol Number
U1111-1292-0487
UTN
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Shilpi Sinha
Designation
Associate Director, Country Head RCO India
Affiliation
Bristol Myers Squibb India Pvt. Ltd.
Address
Bristol Myers Squibb India Pvt. Ltd.
One International Centre, 6th Floor, Tower 1, Senapati Bapat Marg, Elphinstone (W), Mumbai - 400013 (Suburban), MAHARASHTRA,
India
Mumbai (Suburban) MAHARASHTRA 400013 India
Phone
02266288600
Fax
Email
Shilpi.Sinha@bms.com
Details of Contact Person Scientific Query
Name
Dr Kartik Doshi
Designation
Associate Director, Head Medical India
Affiliation
Bristol Myers Squibb India Pvt. Ltd.
Address
Bristol Myers Squibb India Pvt. Ltd.
One International Centre, 6th Floor, Tower 1, Senapati Bapat Marg, Elphinstone (W), Mumbai - 400013 (Suburban), MAHARASHTRA,
India
Mumbai (Suburban) MAHARASHTRA 400013 India
Phone
02266288600
Fax
Email
Kartik.Doshi@bms.com
Details of Contact Person Public Query
Name
Dr Kartik Doshi
Designation
Associate Director, Head Medical India
Affiliation
Bristol Myers Squibb India Pvt. Ltd.
Address
Bristol Myers Squibb India Pvt. Ltd.
One International Centre, 6th Floor, Tower 1, Senapati Bapat Marg, Elphinstone (W), Mumbai - 400013 (Suburban), MAHARASHTRA,
India
MAHARASHTRA 400013 India
Phone
02266288600
Fax
Email
Kartik.Doshi@bms.com
Source of Monetary or Material Support
Bristol Myers Squibb India Pvt. Ltd.
One International Centre, 6th Floor, Tower 1,
Senapati Bapat Marg, Elphinstone (W), Mumbai- 400013
India
Primary Sponsor
Name
Bristol Myers Squibb India Pvt Ltd
Address
One International Centre, 6th Floor, Tower 1, Senapati Bapat Marg, Elphinstone (W), Mumbai - 400013 (Suburban), MAHARASHTRA,
India
Type of Sponsor
Pharmaceutical industry-Global
Details of Secondary Sponsor
Name
Address
NIL
NIL
Countries of Recruitment
Argentina Austria Brazil Canada Chile China Democratic People's Republic of Korea France Germany Greece Hungary India Italy Japan Poland Romania Spain Switzerland Turkey United States of America
Sites of Study
No of Sites = 13
Name of Principal
Investigator
Name of Site
Site Address
Phone/Fax/Email
Dr Prabhat Malik
All India Institutes of Medical Sciences
Room No. 245, Dept of Medical Oncology, 2nd floor, Dr B R Ambedkar Institute of Rotary Cancer hospital, AIIMS, Ansari nagar, New Delhi - 110029 New Delhi DELHI
91-9968325318
drprabhatsm@gmail.com
Dr Priya Tiwari
Artemis Hospital
Artemis Hospital, Department of Medical oncology, Lower Ground floor, Main building, Artemis hospital, Sector-51, Gurugram, Haryana - 122001, India Gurgaon HARYANA
91-8377828241
priya.tiwari@artemishospitals.com
Dr Ankur Bahl
Fortis Memorial Research Institute
Department of Medical Oncology, Lower Ground floor, Fortis Memorial Research Institute, Sec 44, Gurugram, Haryana - 122002, India Gurgaon HARYANA
91-9811380301
drankurbahl@gmail.com
Dr Kshitij Domadia
HCG Cancer Centre
HCG Cancer Centre, Sola-Science City Road, Nr. Sola Bridge, S.G. Highway, Ahmedabad - 380060, Gujarat, India Ahmadabad GUJARAT
91-9427740225
krdomadia@gmail.com
Dr Chirag Desai
Hemato Oncology Clinic Ahmedabad Pvt Ltd
HOC Vedanta (Hemato Oncology Clinic Ahmedabad Pvt Ltd) Niramaya Complex Ground floor to third floor, Beside Pandit Dindayal Upadhyay Auditorium, Rajpath Club Road, Off S G Highway, Ahmedabad, Gujarat – 380054, India Ahmadabad GUJARAT
91-9824047561
chiragdesai.oncology@gmail.com
Dr Amit Rauthan
Manipal Hospitals
Oncology Department, Manipal hospital, # 98, OLD Airport Road, Bangalore - 560017, Karnataka, India Bangalore KARNATAKA
91-9880463958
amitrauthan@yahoo.com
Dr Meher Lakshmi Konatam
Nizams Institute of Medical Sciences
Department of Medical Oncology, Room No 26, Out patient block, Nizams Institute of Medical Sciences, Punja Gutta - 500082, Hyderabad, India Hyderabad TELANGANA
91-9440592569
drmeherlak@gmail.com
Dr Ullas Batra
Rajiv Gandhi Cancer Institute & Research Centre
Room 3153, 1st floor, D block, Rajiv Gandhi Cancer Institute and Research Centre, D-18, Sir Chotu Ram Marg, Rohini Institutional Area, Sector - 5, Rohini, Delhi - 110085, India East DELHI
91-9711080001
ullasbatra@gmail.com
Dr Anoop Manoharan
Regional Cancer Centre hospital
Medical Oncology Department, Regional Cancer Centre, Medical college Campus, Thiruvananthapuram - 695011, Kerala, India Thiruvananthapuram KERALA
91-9447134973
dranooptm@gmail.com
Dr Minish Jain
Ruby Hall Clinic
Ruby Hall Clinic, 40, Sassoon Road, Pune - 411001, Maharashtra, India Pune MAHARASHTRA
91-9823133390
minishjain009@gmail.com
Dr Tushar Patil
Sahyadri Super Speciality Hospital
Sahyadri Super Specialty Hospital, 30 - C Erandwane, Karve Road, Pune - 411004, Maharashtra, India Pune MAHARASHTRA
91-9552522556
tussipats@hotmail.com
Dr Sewanti Limaye
Sir H. N. Reliance Foundation Hospital and Research Centre
3rd floor, Kapol Niwas, Tower building, Raja Rammohan Roy Road, Prarthana Samaj, Charni Road - 400004, Mumbai, India Mumbai (Suburban) MAHARASHTRA
91-9619607339
Sewanti.Limaye@rfhospital.org
Dr Vanita Noronha
Tata Memorial Centre
303, OPD, 3rd floor, Homi Bhabha block, Dr Ernest Borges Road, Parel - 400012, Mumbai, India Mumbai (Suburban) MAHARASHTRA
91-9769328047
vanita.noronha@gmail.com
Details of Ethics Committee
No of Ethics Committees= 13
Name of Committee
Approval Status
Artemis Health Sciences Institutional Ethics Committee
Approved
Ethics Committee of CIMS (Care Institute of Medical Sciences)
Approved
Ethics Committee Of Manipal Hospitals
Approved
HCG MULTI SPECIALTY ETHICS COMMITTEE
Approved
Human Ethics Committee
Submittted/Under Review
IEC, Fortis Memorial Research Institute
Approved
Institute Ethics Committee All India Institute of Medical Sciences
Submittted/Under Review
Institutional Ethics Committee of Sir H. N Reliance Foundation Hospital & Research Centre
Submittted/Under Review
Institutional Ethics Committee Poona Medical Foundation
Approved
Institutional Review Board Rajiv Gandhi Cancer Institute and Research Centre
(1) ICD-10 Condition: C349||Malignant neoplasm of unspecifiedpart of bronchus or lung,
Intervention / Comparator Agent
Type
Name
Details
Comparator Agent
Crizotinib
250mg capsules
Crizotinib will be administered at a dose of 250 mg BID orally (with or without food). The dose and treatment duration for crizotinib is in alignment with the approved product label and has been shown to be safe and provide clinical benefit in patients with ROS1-positive NSCLC.
Intervention
Repotrectinib
40mg,160-mg capsules
Repotrectinib will be administered at a dose of 160 mg QD orally (with or without food) for the first 14 days, after which the dosing frequency will increase to 160 mg BID if all safety criteria are met:
· Otherwise, participants will continue to receive repotrectinib 160 mg QD. Dose escalation to 160 mg BID beyond the first 14 days of QD treatment, if tolerated, will be allowed and not considered a protocol deviation. After 30 days of 160 mg QD treatment, the Medical Monitor should be notified upon dose escalation.
Inclusion Criteria
Age From
18.00 Year(s)
Age To
99.00 Year(s)
Gender
Both
Details
1. Participant has histologically or cytologically confirmed diagnosis of locally advanced or metastatic NSCLC (Stage IIIB, IIIC, IVA, or IVB per 8th edition American Joint Committee on Cancer classification).
2. Participant has a ROS1 gene rearrangement or fusion as detected by a local test. (Central testing is required if local test is not acceptable by Sponsor-required criteria.)
3. At least 1 measurable lesion according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), as assessed by the investigator.
4. Participants must not be exposed previously with TKIs that demonstrated activities in ROS1-positive NSCLC (eg, crizotinib, ceritinib, lorlatinib, brigatinib, entrectinib, ensartinib, DS605 1 b, NVL-520, taletrectinib, foretinib, and cabozantinib).
5. Up to 1 prior line of systemic treatment for NSCLC is permitted (chemotherapy-based, immunotherapy-based, chemotherapy + immunotherapy combination regimens, non-ROS1 TKI regimens, or concurrent chemoradiation regimens [when administered in the context of definitive thoracic radiotherapy]). Prior (neo)-adjuvant treatment for resectable NSCLC does not count as a prior line of therapy if no disease recurrence within 6 months of the completion of the (neo)-adjuvant therapy.
6. Eastern Cooperative Oncology Group Performance Status less than equal to 2
ExclusionCriteria
Details
1. Symptomatic brain metastases or symptomatic leptomeningeal involvement.
2. History of previous cancer requiring therapy within the previous 2 years, except for NSCLC under study, squamous cell or basal-cell carcinoma of the skin, or any in situ carcinoma that has been completely resected.
3. Known tumor targetable co-mutations or rearrangements (ie, epidermal growth factor receptor [EGFR] or anaplastic lymphoma kinase [ALK]).
4. Clinically significant cardiovascular disease (either active or within 6 months prior to enrollment): myocardial infarction, unstable angina, coronary or peripheral artery bypass graft, symptomatic congestive heart failure (New York Heart Association Classification Class more than II), cerebrovascular accident or transient ischemic attack, symptomatic bradycardia, requirement for anti-arrhythmic medication. Ongoing cardiac dysrhythmias of Common Terminology Criteria of Adverse Events version 5.0 Grade more than equal to 2.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
To compare the PFS per BICR of repotrectinib and crizotinib in all randomized participants with locally advanced or metastatic TKI-naïve ROS1-positive NSCLC
Until disease progression,death, or end of study (up to 5 years or time of final OS analysis[approximately 130events]), whichever occurs earlier.
Secondary Outcome
Outcome
TimePoints
To compare the OS of repotrectinib & crizotinib in all randomized participants with locally advanced or metastatic TKI-naïve ROS1-positive NSCLC
Up to 5 years from last participants randomized, or until the time of final OS analysis(approximately 130events), whichever occurs later.
To assess the tumor response of repotrectinib & crizotinib in all randomized participants with locally advanced or metastatic TKI-naïve ROS1-positive NSCLC
Until disease progression, death, or end of study (up to 5 years or time of final OS analysis[approximately 130events]), whichever occurs earlier.
To assess the PFS per investigator of repotrectinib & crizotinib in all randomized participants with locally advanced or metastatic TKI-naïve ROS1-positive NSCLC
Until disease progression, death, or end of study (up to 5 years or time of final OS analysis[approximately 130events]), whichever occurs earlier.
To assess time to intracranial progression of repotrectinib & crizotinib in all randomized participants with locally advanced or metastatic TKI-naïve ROS1-positive NSCLC
Until disease progression, death, or end of study (up to 5 years or time of final OS analysis[approximately 130events]), whichever occurs earlier.
To assess the safety of repotrectinib and crizotinib in all treated participants with locally advanced or metastatic TKI-naïve ROS1-positive NSCLC
Incidence of AEs, SAEs, AEs leading to study intervention discontinuation, drug-related AEs, and deaths
To assess disease-related symptoms for repotrectinib and crizotinib in all randomized participants with locally advanced or metastatic TKI-naïve ROS1-positive NSCLC
Proportion of participants without meaningful symptom deterioration (at least 3-point change) as measured by the NSCLC-SAQ total score
Target Sample Size
Total Sample Size="230" Sample Size from India="12" 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 3
Date of First Enrollment (India)
01/11/2024
Date of Study Completion (India)
Applicable only for Completed/Terminated trials
Date of First Enrollment (Global)
21/12/2023
Date of Study Completion (Global)
Applicable only for Completed/Terminated trials
Estimated Duration of Trial
Years="5" Months="0" Days="0"
Recruitment Status of Trial (Global)
Open to Recruitment
Recruitment Status of Trial (India)
Not Yet Recruiting
Publication Details
N/A
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
The data collected during this study are confidential and proprietary to the Sponsor or designee. Any publications or abstractsarising from this study must adhere to the publication requirements set forth in the Clinical Trial Agreement (CTAg) governing [study site or investigator] participation in the study. These requirements include, but are not limited to, submitting proposedpublications to the Sponsor or designee at the earliest practicable time prior to submission or presentation and otherwise within the period set forth in the CTAg.Scientific publications (such as abstracts, congress podium presentations and posters, and manuscripts) of the study results will be a collaborative effort between the study Sponsor and the external authors. No public presentation or publication of any interim results may be made by any Principal Investigator, sub-investigator,or any other member of the study staff without the prior written consent of the Sponsor.Authorship of publications at the Sponsor is aligned with the criteria of the International Committee of Medical Journal Editors (ICMJE;www.icmje.org). Authorship selection is based on significant contributions to the study (ie, ICMJE criterion #1). Authors must meet all 4 ICMJE criteria for authorship:
1)Substantial intellectual contribution to the conception or design of the work; or the acquisition of data (ie, evaluable participants with quality data), analysis, or interpretation of data for the work(eg, problem solving, advice, evaluation, insights,and conclusion)2)Drafting the work or revising it critically for important intellectual content3)Final approval of the version to be published4)Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolvedThose who make the most significant contributions, as defined above, will be considered by the Sponsor for authorship of the primary publication. Sub-investigators will generally not be considered for authorship in the primary publication. Geographic representation will also be considered.Authors will be listed by order of significant contributions (highest to lowest), with the exception of the last author. Authors in first and last position have provided the most significant contributions to the work. For secondary analyses and related publications, author list and author order may vary from primary to reflect additional contributions.