CTRI/2022/03/040959 [Registered on: 09/03/2022] Trial Registered Prospectively
Last Modified On:
31/07/2025
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Randomized, Parallel Group, Multiple Arm Trial
Public Title of Study
Study of Dato-DXd Versus Standard Chemotherapy in patient with Inoperable or Metastatic
Hormone Receptor-Positive, HER2-Negative Breast Cancer who has been failed on previous chemotherapy
Scientific Title of Study
A Phase 3, Open-label, Randomized Study of Dato-DXd Versus Investigator’s Choice of Chemotherapy in Participants With Inoperable or Metastatic Hormone Receptor-Positive, HER2-Negative Breast Cancer Who Have Been Treated With One or Two Prior Lines of Systemic Chemotherapy (TROPION-Breast01)
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
2020-005620-12
EudraCT
D9268C00001 Version, 2.0 dated 27 Aug 2021
Protocol Number
NCT05104866
ClinicalTrials.gov
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Senior Director, Oncology Country Head Site Management and Monitoring – India
Affiliation
AstraZeneca Pharma India Ltd
Address
Block N1, 12th Floor, Manyata Embassy Business Park Rachenahalli, Outer Ring Road, PIN – 560045
Bangalore KARNATAKA 560045 India
Phone
91-9845079472
Fax
Email
Sandeep.AV@astrazeneca.com
Source of Monetary or Material Support
ASTRAZENECA AB
151 85 Södertälje, Sweden
Primary Sponsor
Name
ASTRAZENECA AB
Address
151 85 Södertälje, Sweden
Type of Sponsor
Pharmaceutical industry-Global
Details of Secondary Sponsor
Name
Address
AstraZeneca Pharma India Limited
Block N1, 12th Floor, Manyata Embassy
Business Park Rachenahalli, Outer Ring Road,Bangalore – 560045
Countries of Recruitment
Argentina Belgium Brazil Canada China France Germany Hungary India Italy Japan Mexico Netherlands Poland Russian Federation Spain Taiwan United Kingdom United States of America Republic of Korea South Africa
Department of Medical
Oncology, All India Institute of Medical Sciences,
Veerbhadra Marg, Rishikesh, Uttarakhand- 249203
Dehradun UTTARANCHAL
9958474477
amit.monc@aiimsrishikesh.edu.in
Dr Shailesh Bondarde
Apex Wellness Hospital
Department of Medical Oncology
Survey no 799, Plot no 187, Behind prakash petrol pump Govind Nagar, Nashik 422009, Maharashtra Nashik MAHARASHTRA
9822012427
shaileshbondarde1971@gmail.com
Dr Mukesh Patekar
Artemis Hospital
Department of Medical Oncology Artemis Hospitals, Sector-51, Gurgaon, Haryana, India 122001 Gurgaon HARYANA
9968959935
Mukesh.patekar@artemishospitals.com
Dr Amit Kumar Dhiman
Deep Hospital
Department of Medical Oncology
481, Model
Town, Ludhiana, Punjab,
Pin-141002, India
Ludhiana PUNJAB
9779898339
dramit.meet@gmail.com
Dr Nandish Kumar Jeevangi
HCG Cancer Center
Department of Medical Oncology No. 1-10/A, Khuba Plot, Station Road, Kalaburagi-585102 Gulbarga KARNATAKA
7259029517
docnandishkumar@gmail.com
Dr Shaunuk Valame
HCG Manavata Cancer Center
Department of Medical Oncology
HCG Manavata Oncology LLP. Behind Shivang Auto, Mumbai Naka, Nashik- 422 002 Nashik MAHARASHTRA
9753339462
drshaunak@mcrinasik.com
Dr Rajani Priya Yedla
MAHATMA GANDHI CANCER HOSPITAL- RESEARCH INSTITUTE,
Dept. of Medical Oncology
Plot No:1, Sector:7, MVP Colony, Visakhapatnam, PIN 530017 Visakhapatnam ANDHRA PRADESH
9640953911
drrajinipriya@gmail.com
Dr Chandrkanth M V
Narayana Superspeciality Hospital
Department of Medical Oncology 120/1, Andul Road, Howrah-711103 Haora WEST BENGAL
7738519198
drmvch@gmail.com
Dr Lalit Mohan Sharma
Sri Ram Cancer and Superspeciality Centre
Department of Medical Oncology
Mahatma Gandhi Medical College and Hospital, RIICO Institutional Area, Tonk Rd, Sitapura, Jaipur, Rajasthan 302022 Jaipur RAJASTHAN
9928602244
drlalit2003@gmail.com
Dr Somnath Roy
Tata Medical Center
Department of Medical Oncology 14-MAR(EW) Newtown action Area I, Kolkata-700160, West Bengal Kolkata WEST BENGAL
9051732283
somnath.roy1@tmckolkata.com
Dr Ankit Baldevbhai Patel
Unique Hospital- Multispecialty & Research Institute
Dept. of Medical Oncology
Opp Kiran Motor, Nr Canal, Civil Hospital, Char Rasta- Sosyo Circle Lane, Off Ring Road, PIN- 395002 Surat GUJARAT
9825404202
drankitoncologist@gmail.com
Dr Akhila K B
VGM Hospital
Department of Medical Oncology, 2100, Trichy Road, Rajalakshmi mills stop, Coimbatore, 641005, Tamil Nadu Coimbatore TAMIL NADU
9442645184
kbakila@yahoo.co.in
Dr Nikhil Gadyalipatil
Yashoda Hospital
Department of Medical Oncology Rajbhavan Road, Somajiguda, Hyderabad-500082, Telengana, India Hyderabad TELANGANA
Institutional Ethics Committee, 481, Model Town, Ludhiana, Punjab, Pin- 141002
Submittted/Under Review
Institutional Ethics Committee, AIIMS Rishikesh
Approved
Institutional Ethics Committee, HCG Cancer center, Karnataka
Approved
Institutional Ethics Committee, Mahatma Gandhi Medical College and Hospital, Rajasthan
Approved
Institutional Ethics Committee, Yashoda Academy of Medical Education and Research, Telangana
Approved
Institutional Review Board Tata Medical Center, West Bengal
Approved
Institutional Review Board, MAHATMA GANDHI CANCER HOSPITAL- RESEARCH INSTITUTE, Visakhapatnam
Approved
Manavata Clinical Research Institute Ethics Committee, Nashik
Submittted/Under Review
NSH Ethics Committee Narayana Superspeciality Hospital, West Bengal
Submittted/Under Review
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: C509||Malignant neoplasm of breast of unspecified site,
Intervention / Comparator Agent
Type
Name
Details
Intervention
Datopotamab deruxtecan
Dato-DXd monotherapy 6.0 mg/kg IV Q3W on Day 1 of each 21 day cycle
Comparator Agent
Eribulin, Vinorelbine, Capecitabine or Gemcitabine
Capecitabine (1000 or 1250 mg/m2 oral BID on Days 1 to 14, Q3W)
Gemcitabine (1000 mg/m2 IV Day 1 and Day 8, Q3W)
Eribulin mesylate (1.4 mg/m2 IV on Days 1 and 8, Q3W)
Vinorelbine (25 mg/m2 IV on Days 1 and 8, Q3W)
Inclusion Criteria
Age From
18.00 Year(s)
Age To
99.00 Year(s)
Gender
Both
Details
I. Age must be above or equal to 18 years, male or female
II. Inoperable or metastatic HR-positive, HER2-negative breast cancer (per ASCO/CAP guidelines, on local laboratory results)
III. Progressed on or not suitable for endocrine therapy per investigator assessment, and treated with 1 to 2 lines of prior standard of care chemotherapy in the inoperable/metastatic setting. Participant must have documented progression on their most recent line of chemotherapy.
IV. Eligible for one of the chemotherapy options listed as ICC (eribulin, capecitabine, vinorelbine, gemcitabine), per investigator assessment.
V. ECOG PS of 0 or 1.
VI. At least 1 measurable lesion not previously irradiated that qualifies as a RECIST 1.1 Target Lesion at baseline and can be accurately measured at baseline as ≥ 10 mm in the longest diameter (except lymph nodes, which must have short axis ≥ 15 mm) with CT or MRI, which is suitable for accurate repeated measurements.
VII. Participants with a history of previously treated neoplastic spinal cord compression, or clinically inactive brain metastases, who require no treatment with corticosteroids or anticonvulsants, may be included in the study, if they have recovered from the acute toxic effect of radiotherapy. A minimum of 2 weeks must have elapsed between the end of radiotherapy and study enrolment.
VIII. Adequate organ and bone marrow function within 7 days before day of first dosing as follows: - Hemoglobin: ≥ 9.0 g/dL, Absolute neutrophil count: ≥ 1500/mm3, Platelet count: ≥ 100000/mm3, Total bilirubin: ≤ 1.5 × ULN if no liver metastases; or ≤ 3 × ULN in the presence of documented Gilberts syndrome (unconjugated hyperbilirubinemia) or liver metastases at baseline. ALT and AST: ≤ 2.5 × ULN for AST/ALT; however, if elevation is due to liver metastases, ≤ 5.0 × ULN is allowed, Calculated creatinine clearance: ≥ 30 mL/min as calculated using the Cockcroft-Gault equation (using actual body weight)
IX. LVEF ≥ 50% by either an echocardiogram or MUGA within 28 days of first dosing.
X. Has had an adequate treatment washout period before Cycle 1 Day 1, defined as: - Major surgery: ≥ 3 weeks. Radiation therapy including palliative radiation to chest: ≥ 4 weeks (palliative radiation therapy to other areas ≥ 2 weeks). Anticancer therapy including hormonal therapy: ≥ 3 weeks (for small molecule targeted agents: ≥ 2 weeks or 5 half-lives, whichever is longer) Antibody-based anticancer therapy: ≥ 4 weeks with the exception of receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitors (eg, denosumab for the treatment of bone metastases),Chloroquine/hydroxychloroquine: > 14 days.
XI. All participants must have available a FFPE tumor sample (block preferred, or a minimum of 20 freshly cut slides), at the time of screening. This can be from either the primary disease setting (surgical resection or diagnostic sample), or from a metastatic lesion (excluding bone) for tissue-based analysis (including but not restricted/limited to IHC staining of potential predictive biomarkers as well as tumor mutational analysis).
XII. Minimum life expectancy of 12 weeks at screening.
XIII. Negative pregnancy test (urine and/or serum) for women of childbearing potential
XIV. Female participants must be post-menopausal for at least 1 year, surgically sterile, or using one highly effective form of birth control
XV. Male participants who intend to be sexually active with a female partner of childbearing potential must be surgically sterile or using an acceptable method of contraception.
XVI. Capable of giving signed informed consent
XVII. Provision of signed and dated written Optional Genetic Research Information informed consent prior to collection of sample for optional genetic research that supports Genomic Initiative.
ExclusionCriteria
Details
I. As judged by the investigator, any evidence of diseases (such as severe or uncontrolled systemic diseases, uncontrolled hypertension, history of allogeneic organ transplant, and active bleeding diseases, ongoing or active infection, or significant or cardiac or psychological conditions) which, in the investigators opinion, makes it undesirable for the participant to participate in the study or that would jeopardize compliance with the protocol.
II. History of another primary malignancy except for malignancy treated with curative intent with no known active disease within 3 years before the first dose of study intervention and of low potential risk for recurrence.
III. Persistent toxicities caused by previous anticancer therapy (excluding alopecia), not yet resolved to CTCAE Version 5.0 Grade ≤ 1 or baseline.
IV. Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals; suspected infections (eg, prodromal symptoms); or inability to rule out infections.
V. Known active or uncontrolled hepatitis B or C infection; or positive for hepatitis B or C virus based on the evaluation of results of tests for hepatitis B (HBsAg, anti-HBs, anti-HBc, or HBV DNA) or hepatitis C (HCV antibody or HCV RNA) infection at screening.
VI. Known HIV infection that is not well controlled. All of the following criteria are required to define an HIV infection that is well controlled: undetectable viral RNA load, CD4+ counts/levels > 250, no history of AIDs-defining opportunistic infection within the past 12 months, and stable for at least 4 weeks on same anti-HIV retroviral medications.
VII. Uncontrolled or significant cardiac disease, including myocardial infarction or uncontrolled/unstable angina within 6 months prior to C1D1, CHF (New York Heart Association Class II to IV), uncontrolled or significant cardiac arrhythmia, or uncontrolled hypertension (resting systolic blood pressure > 180 mmHg or diastolic blood pressure > 110 mmHg).
VIII. Investigator judgment of 1 or more of the following: − Mean resting corrected QTcF interval > 470 ms, obtained from triplicate ECGs performed at screening.
IX. History of (non-infectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
X. Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (ie, pulmonary emboli within three months of first dosing, severe asthma, severe COPD, restrictive lung disease, pleural effusion etc), or any autoimmune, connective tissue or inflammatory disorders with pulmonary involvement (ie, Rheumatoid arthritis, Sjogrens, sarcoidosis etc), or prior pneumonectomy.
XI. Leptomeningeal carcinomatosis.
XII. Clinically significant corneal disease.
XIII. Known active tuberculosis infection (clinical evaluation that may include clinical history, physical examination and radiographic findings, or tuberculosis testing in line with local practice).
XIV. Any of the following prior anticancer therapies: − Any treatment (including ADC) containing a chemotherapeutic agent targeting topoisomerase I or Prior treatment with same ICC agent
XV. Any concurrent anticancer treatment, with the exception of bisphosphonates, denosumab, for the treatment of bone metastases.
XVI. Concurrent use of hormonal therapy for non cancer related conditions (eg, hormone replacement therapy, except topical).
XVII. Major surgical procedure (excluding placement of vascular access) or significant traumatic injury within 3 weeks of the first dose of study intervention or an anticipated need for major surgery during the study.
XVIII. Receipt of live, attenuated vaccine within 30 days prior to the first dose of study treatment.
XIX. Concomitant use of chronic systemic (IV or oral) corticosteroids or other immunosuppressive medications except for managing adverse events (inhaled steroids or intra articular steroid injections are permitted in this study).
XX. Previous treatment in the present study.
XXI. Participation in another clinical study with a study intervention or investigational medicinal device administered in the last 4 weeks prior to first dosing, randomization into a prior T-DXd (trastuzumab deruxtecan) study regardless of treatment assignment, or concurrent enrolment in another clinical study, unless it is an observational (noninterventional) clinical study or during the follow-up period of an interventional study.
XXII. Participants with a known hypersensitivity to Dato-DXd, or any of the excipients of the product (including, but not limited to, polysorbate 80).
XXIII. Known history of severe hypersensitivity reactions to other monoclonal antibodies.
XXIV. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
XXV. Judgment by the investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions and requirements.
XXVI. For women only, currently pregnant (confirmed with positive pregnancy test) or breastfeeding, or who are planning to become pregnant.
Method of Generating Random Sequence
Stratified block randomization
Method of Concealment
Centralized
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
To demonstrate the superiority of Dato-DXd compared to ICC by assessment of:
1. PFS in participants with inoperable or metastatic HR-positive, HER2-negative breast cancer, who have been treated with 1 or 2 lines of chemotherapy in the inoperable/metastatic setting, per BICR.
2. OS in participants with inoperable or metastatic HR-positive, HER2-negative breast cancer, who have been treated with 1 or 2 lines of chemotherapy in the inoperable/metastatic setting.
To demonstrate the superiority of Dato-DXd compared to ICC by assessment of PFS in participants with inoperable or metastatic HR-positive, HER2-negative breast cancer, who have been treated with 1 or 2 lines of chemotherapy in the inoperable/metastatic setting, per BICR.
OS is defined as time from randomization until the date of death due to any cause.
Secondary Outcome
Outcome
TimePoints
To demonstrate the superiority of Dato DXd compared to ICC by assessment of ORR in participants with inoperable or metastatic HR positive, HER2 negative breast cancer, who have been treated with 1 or 2 lines of chemotherapy in the inoperable metastatic setting, per BICR and per investigator assessment.
ORR is defined as the proportion of participants who have a confirmed CR or PR, as determined by the BICR Investigator assessment, per RECIST 1.1.
2.5 Years
To demonstrate the superiority of Dato-DXd compared to ICC by assessment of ORR in participants with inoperable or metastatic HR-positive, HER2-negative breast cancer, who have been treated with 1 or 2 lines of chemotherapy in the inoperable/metastatic setting, per BICR and per investigator assessment.
ORR is defined as the proportion of participants who have a confirmed CR or PR, as determined by the BICR/Investigator assessment, per RECIST 1.1
2.5 Years
To demonstrate the superiority of Dato-DXd compared to ICC by assessment of DoR in participants with inoperable or metastatic HR-positive, HER2-negative breast cancer who have been treated with 1 or 2 lines of chemotherapy in the inoperable/metastatic setting
DoR is defined as the time from the date of first documented confirmed response until date of documented progression per RECIST 1.1, as assessed by BICR/Investigator assessment or death due to any cause.
2.5 Years
To demonstrate the superiority of Dato-DXd compared to ICC by assessment of PFS in participants with inoperable or metastatic HR-positive, HER2-negative breast cancer who have been
PFS is defined as time from randomization until progression per RECIST 1.1, as assessed by investigator assessment, or death due to any cause.
2.5 Years
To demonstrate the superiority of Dato-DXd compared to ICC by assessment of DCR in participants with inoperable or metastatic HR-positive, HER2-negative breast cancer, who have been treated with 1 or 2 lines of chemotherapy in the inoperable/metastatic setting, per BICR and per investigator assessment.
DCR at 12 weeks is defined as the percentage of participants who have a confirmed CR or PR or who have SD, per RECIST 1.1, as assessed BICR/per investigator assessment and derived from the raw tumor data for at least 11 weeks after randomization.
2.5 Years
To assess pain in participants treated with Dato-DXd compared to ICC.
TTD in pain as measured by the pain scale from EORTC QLQ-C30
2.5 Years
To assess physical functioning in participants treated with Dato-DXd compared to ICC
TTD in physical functioning as measured by the physical functioning scale from EORTC QLQ-C30
2.5 Years
To assess global health status/quality of life (GHS/QoL) in participants treated with Dato-DXd compared to ICC.
TTD in GHS/QoL as measured by the GHS/QoL scale from EORTC QLQ-C30
2.5 Years
To demonstrate the superiority of Dato-DXd compared to ICC by assessment of TFST in participants with inoperable or metastatic HR-positive, HER2-negative breast cancer who have been treated with 1 or 2 lines of chemotherapy in the inoperable/metastatic setting.
TFST is defined as the time from randomization until the start date of the first subsequent anti-cancer therapy after discontinuation of randomized treatment, or death due to any cause.
2.5 Years
To demonstrate the superiority of Dato-DXd compared to ICC by assessment of TSST in participants with inoperable or metastatic HR-positive, HER2-negative breast cancer who have been treated with 1 or 2 lines of chemotherapy in the inoperable/metastatic setting.
TSST is defined as the time from randomization to until the start date of the second subsequent anti-cancer therapy after discontinuation of first subsequent treatment, or death due to any cause
2.5 Years
To demonstrate the superiority of Dato-DXd compared to ICC by assessment of PFS2 in participants with inoperable or metastatic HR-positive, HER2-negative breast cancer who have been treated with 1 or 2 lines of chemotherapy in the inoperable/metastatic setting
PFS2 will be defined as the time from the randomization to the earliest of the progression event (following the initial progression), subsequent to first subsequent therapy, or death. The date of second progression will be recorded by the Investigator in the eCRF and defined according to local standard clinical practice.
2.5 Years
To assess the PK of Dato-DXd 6mg/kg IV Q3W.
Plasma concentrations of Dato-DXd, total anti-TROP2 antibody, and MAAA-1181a (payload).
2.5 Years
To investigate the immunogenicity of Dato-DXd 6mg/kg IV Q3W.
Presence of ADA.
2.5 Years
To assess the safety and tolerability profile of Dato-DXd compared to ICC.
Safety and tolerability will be evaluated in terms of adverse events (graded by CTCAE version 5.0), and also in terms of:
ECOG PS
Vital signs, body weight, physical examination
Clinical chemistry, hematology, and urinalysis assessments
ECG, ECHO/MUGA and Ophthalmologic assessments
2.5 Years
Target Sample Size
Total Sample Size="700" Sample Size from India="21" Final Enrollment numbers achieved (Total)= "0" Final Enrollment numbers achieved (India)="0"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This is a Phase 3, randomised, open-label, 2 arm, multicentre, international study assessing the efficacy and safety of Dato-DXd compared with ICC in participants with inoperable or metastatic HR-positive, HER2-negative breast cancer who have been treated with one or two prior lines of systemic chemotherapy in the inoperable or metastatic setting. Approximately 1000 participants will be enrolled to achieve approximately 700 randomly assigned to study intervention
Eligible Participants will be randomised in a 1:1 ratio to one of the following intervention groups:
Arm 1: Dato-DXd ( IV on Day 1, Q3W)
Arm 2: ICC Capecitabine (oral BID on Days 1 to 14, Q3W); choice between the 2 doses will be determined by standard institutional practice.
Gemcitabine (IV Day 1 and Day 8, Q3W)
Eribulin mesylate (IV on Days 1 and 8, Q3W)
Vinorelbine (IV on Days 1 and 8, Q3W)
All participants will receive study intervention until Investigator-defined disease progression according to RECIST 1.1, or until unacceptable toxicity, withdrawal of consent, or another criterion for discontinuation is met. Continued treatment with the same study drug post-progression may be allowed, based on prior discussion with study physician on case-by-case basis. No crossover between study treatment arms will be allowed.