| CTRI Number |
CTRI/2024/03/063553 [Registered on: 04/03/2024] Trial Registered Prospectively |
| Last Modified On: |
31/07/2025 |
| Post Graduate Thesis |
No |
| Type of Trial |
Observational |
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Type of Study
|
Retrospective |
| Study Design |
Other |
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Public Title of Study
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A study to see the prevalence of HER2 low, clinical characteristics, treatment patterns, and outcomes in patients with HER2 negative locally advanced or metastatic breast cancer who progressed on systemic anticancer therapy. |
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Scientific Title of Study
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A Multicenter, Retrospective, Noninterventional Study to Determine the
Prevalence of HER2-low, Clinical Characteristics, Treatment Patterns, and
Associated Outcomes in Patients Previously Identified With HER2 negative
Locally-advanced or Metastatic Breast Cancer Who Progressed on Systemic Anticancer Therapy |
| Trial Acronym |
iRetroBC-HER2L Study |
Secondary IDs if Any
Modification(s)
|
| Secondary ID |
Identifier |
| D9673R00037 Version 1.3 Dated 14 April 2025 |
Protocol Number |
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Details of Principal Investigator or overall Trial Coordinator (multi-center study)
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| Name |
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| Designation |
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| Affiliation |
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| Address |
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| Phone |
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| Fax |
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| Email |
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Details of Contact Person
Scientific Query
|
| Name |
Likith H V |
| Designation |
Medical Advisor |
| Affiliation |
AstraZeneca Pharma India Ltd |
| Address |
AstraZeneca Pharma India Ltd
Block N1,12th Floor, Manyata Embassy Business Park, Rachenahalli, Outer Ring Road, Bangalore
Bangalore
KARNATAKA
560045
India |
| Phone |
8892062157 |
| Fax |
|
| Email |
likith.hv@astrazeneca.com |
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Details of Contact Person
Public Query
|
| Name |
Jinu Johnson |
| Designation |
Project Manager- Trials and Publications |
| Affiliation |
AstraZeneca Pharma India Ltd |
| Address |
AstraZeneca Pharma India Ltd
Block N1,12th Floor, Manyata Embassy Business Park, Rachenahalli, Outer Ring Road, Bangalore
Bangalore
KARNATAKA
560045
India |
| Phone |
8078484767 |
| Fax |
|
| Email |
jinu.johnson@astrazeneca.com |
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Source of Monetary or Material Support
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Primary Sponsor
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| Name |
AstraZeneca Pharma India Ltd |
| Address |
Block N1,12th Floor, Manyata Embassy Business Park, Rachenahalli, Outer Ring Road, Bangalore 560045, INDIA. |
| Type of Sponsor |
Pharmaceutical industry-Global |
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Details of Secondary Sponsor
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Countries of Recruitment
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Hong Kong
India
Indonesia
Malaysia
Philippines
Singapore
Thailand
Viet Nam
Argentina
Brazil
Chile
Dominican Republic
Mexico
Panama
Turkey |
Sites of Study
Modification(s)
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| No of Sites = 10 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Atul Batra |
All India Institute of Medical Sciences (AIIMS) |
Ansari Nagar New Delhi 110029
South West
DELHI |
1129575232
batraatul.85@gmail.com |
| Dr K Pavithran |
Amrita Institute of Medical Sciences |
AIMS Ponekkara PO, Kochi- 682041
Ernakulam
KERALA |
9895367090
Pavithrank@aims.amrita.edu |
| Dr Senthil Rajappa |
Basavatarakam Indo American Cancer Hospital & Research Institute |
Department of Medical
Oncology, Block-01,
First Floor, Room No.
123, Road No. 10,
Banjara hills,
Hyderabad
Hyderabad
TELANGANA |
9849213102
senthilrajappa@gmail.com |
| Dr Sajjan Rajpurohit |
Dr. B.L. Kapur Memorial Hospital |
Department of Medical Oncology,Pusa Road, New Delhi- 110005
New Delhi
DELHI |
9999660200
sajjanrajpurohit@yahoo.com |
| Dr Soumya Surath Panda |
Institute of Medical Sciences and SUM Hospital |
Department of Medical Oncology, Siksha O Anusandhan University, Bhubaneshwar- 751003
Khordha
ORISSA |
8895370579
soumyasurathpanda@soa.ac.in |
| Dr Akhil Kapoor |
Mahamana Pandit Madan Mohan Malviya Cancer Centre |
Banaras Hindi University Campus, Sundar Bagiya Colony, Sundarpur, Varanasi- 221005
Varanasi
UTTAR PRADESH |
9950482121
kapoorakhil1987@gmail.com |
| Dr Amit Rauthan |
Manipal Hospital |
No. 98, Old Airport Road, Kodihalli, Bengaluru- 560017
Bangalore
KARNATAKA |
9880463958
amit.rauthan@manipalhospitals.com |
| Dr Gautam Goyal |
Max Superspeciality Hospital |
Near Civil Hospital, Phase VI, Punjab- 160055
Rupnagar
PUNJAB |
8195848111
Gautam.Goyal@maxhealthcare.com |
| Dr Anurag Mehta |
Rajiv Gandhi Cancer Institute and Research Center |
Squadron Leader Mohinder Kumar Jain Marg, Block K, Neeti Bagh, New Delhi
South
DELHI |
9810836274
dcdoval@gmail.com |
| Dr Anbarasan Sekar |
Tata Memorial Hospital |
TMH Annexe Building,Jerbai Wadia Road, Dadar East
Mumbai
MAHARASHTRA |
8124227205
anbarasan157@gmail.com |
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Details of Ethics Committee
Modification(s)
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| No of Ethics Committees= 10 |
| Name of Committee |
Approval Status |
| Ethics Committee of Manipal Hospitals |
Approved |
| Institute Ethics committee All India Institute of Medical Science |
Approved |
| Institutional Ethics Committee Amrita lnstitute of Medical Sciences |
Approved |
| Institutional Ethics Committee IMS and SUM Hospital |
Approved |
| Institutional Ethics Committee Mahamana Pandit Madan Mohan Malviya Cancer Centre |
Approved |
| Institutional Ethics Committee Tata Memorial Centre |
Approved |
| Institutional Ethics Committee- B.L. Kapur Memorial Hospital |
Approved |
| Institutional Ethics Committee- Basavatarakam Indo Americal Cancer Hospital and Research Institute |
Approved |
| Institutional Ethics Committee- Max Superspeciality Hospital |
Approved |
| Institutional Review Board of Rajiv Gandhi Cancer Insititute and Research Centre |
Approved |
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Regulatory Clearance Status from DCGI
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Health Condition / Problems Studied
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| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: C509||Malignant neoplasm of breast of unspecified site, |
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Intervention / Comparator Agent
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| Type |
Name |
Details |
| Intervention |
NIL |
NIL |
| Comparator Agent |
NIL |
NIL |
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Inclusion Criteria
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| Age From |
18.00 Year(s) |
| Age To |
99.00 Year(s) |
| Gender |
Both |
| Details |
1. Men or women, ≥18 years of age at study entry
2. Provision of informed consent by the patient or next of kin/legal representative (for
deceased patients at study entry, unless a waiver was granted) according to local
regulations
3. Must have a histological or cytological confirmed previous diagnosis as HER2-negative
(IHC zero, 1+, 2+/ISH-) locally-advanced or mBC between 01 January 2019 and
31 December 2022, regardless of HR status
4. Must have progressed on any systemic anticancer therapy (eg, ET, chemotherapy, CDK4/6
inhibitor, targeted therapies other than anti-HER2, or immunotherapy) in the metastatic
setting with the availability of at least 12 months of follow-up data (from the index date)
in the medical records at the participating site, unless patient died within the first 12
months of diagnosis
a) The HR positive patients will be considered eligible for the study if they have received
ET as adjuvant therapy in the early BC setting and progressed within 24 months, this
scenario will be considered as progression on systematic treatment in the advanced or
metastatic setting
5. Must have historical IHC-stained FFPE tissue from locally-advanced or mBC slides for
HER2 in an acceptable quality to allow for accurate rescoring of HER2 expression |
|
| ExclusionCriteria |
| Details |
1. Have a history of other malignancies, other than basal cell carcinoma of the skin and
squamous cell carcinoma of the skin until 3 years prior to diagnosis of locally-advanced or
mBC
2. Patients with historical HER2 status of IHC 2+/ISH+ or 3+, or HER2 amplified |
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Method of Generating Random Sequence
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Method of Concealment
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Blinding/Masking
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Primary Outcome
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| Outcome |
TimePoints |
Proportion of patients with IHC 1 positive or IHC 2 positive or ISH negative HER2 expression (HER2-low) and
IHC greater than 0 or less than 1 positive or IHC null (no stain at all) based on historical IHC-stained FFPE slides
previously identified among HER2-negative locally-advanced or mBC patients. |
Single Visit |
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Secondary Outcome
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| Outcome |
TimePoints |
Distribution of patients demographic, clinicopathological characteristics, treatment patterns & duration in each LOT in locally-advanced or mBC disease at baseline, from the diagnosis of locally-advanced or mBC, concordance of HER2 IHC scores between historical & rescoring by local & or independent central laboratory post training, & HER2 low expression in HR-positive & HR-negative subgroups.
Disease outcomes (time to first subsequent treatment, time to treatment
discontinuation , overall survival, real-world progression-free survival,
real-world objective response rate) will be assessed for overall study population & HER-2 subsets (HER2 low─IHC1 positive or IHC2 positive or ISH negative, HER2 IHC greater than 0 less than 1 positive, HER2 null, & HER2
zero─HER2 IHC greater than 0 less than 1 positive & HER2 null).The TFST, TTD, rwPFS & rwORR will also be assessed by each LOT. |
Single visit |
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Target Sample Size
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Total Sample Size="2700"
Sample Size from India="200"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
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Phase of Trial
|
N/A |
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Date of First Enrollment (India)
|
14/03/2024 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
14/03/2024 |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
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Estimated Duration of Trial
|
Years="0"
Months="0"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Closed to Recruitment of Participants |
| Recruitment Status of Trial (India) |
Closed to Recruitment of Participants |
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Publication Details
|
N/A |
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Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
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Brief Summary
|
The current treatment landscape of HER2-negative/HER2-low metastatic breast cancer (mBC) comprises of endocrine therapy (ET; based on hormone receptor [HR] status), cyclindependent kinase (CDK)4/6 inhibitors, mammalian target of rapamycin (mTOR) inhibitors, phosphoinositide 3-kinase (PI3K) inhibitors in combination with ET and chemotherapy for patients with HER2-negative/HER2-low and HR-negative BC. There are limited targeted treatment options post progression on primary therapy for HER2-negative/HER2-low mBC. The development of trastuzumab deruxtecan (T-DXd), an antibody-drug-conjugate, has opened up promising avenues for the treatment of HER2-low BC exceeding the efficacies of currently available treatment options. Approximately, 60% of HER2-negative mBCs express low levels of HER2 constituting both HR-positive and HR-negative mBCs, and may significantly benefit from T-DXd with improved clinical and survival outcomes.
This noninterventional, multicenter, retrospective study has been proposed to estimate the prevalence, clinicopathological characteristics, treatment patterns, and clinical outcomes of HER2-low locally-advanced or mBC by accurate rescoring of archived IHC stained formalin-fixed paraffin-embedded (FFPE) slides for HER2 in patients previously identified as HER2-negative from emerging markets of international regions (non-US and non-European region) with largely unknown prevalence estimates of HER2 low mBCs. |