| CTRI Number |
CTRI/2024/04/066324 [Registered on: 25/04/2024] Trial Registered Prospectively |
| Last Modified On: |
23/04/2024 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Non-randomized, Multiple Arm Trial |
|
Public Title of Study
|
A clinical trial to study the effect of low-dose chemotherapy drugs targeting tumor cells and other tumor-supporting cells to enhance the efficacy of immunotherapy drugs in breast cancer patients |
|
Scientific Title of Study
|
Tumor microenvironment modulation therapy in breast-cancer-subtypes and single-cell genomics-based patient stratification for improved low-dose immunotherapy: Preclinical and Clinical study
|
| Trial Acronym |
NIL |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| NIL |
NIL |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Pavithran K |
| Designation |
Professor and HOD |
| Affiliation |
Amrita Institute of Medical Sciences |
| Address |
Room No-2
Dept of Medical Oncology
A-Block,
Amrita Institute of Medical Sciences
Ponekkara P. O., Ernakulam,Kochi,
Kerala-682041,India
Ernakulam
KERALA
682041
India |
| Phone |
9895367090 |
| Fax |
|
| Email |
drkpavithran@gmail.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Manzoor K |
| Designation |
Professor |
| Affiliation |
Amrita Institute of Medical Sciences |
| Address |
Amrita School of Nanosciences and Molecular Medicine,
Amrita Institute of Medical Sciences
Ponekkara P. O.,
Kochi-41,
Kerala, India
Ernakulam
KERALA
682041
India |
| Phone |
9946696286 |
| Fax |
|
| Email |
manzoork@gmail.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr Vijayakumar D K |
| Designation |
Professor and HOD |
| Affiliation |
Amrita Institute of Medical Sciences |
| Address |
Dept of Breast and Gynecological Oncology
Amrita Institute of Medical Sciences
Ponekkara P. O., Kochi-41, Kerala, India
Ernakulam
KERALA
682041
India |
| Phone |
9744870684 |
| Fax |
|
| Email |
dkvijaykumar@gmail.com |
|
|
Source of Monetary or Material Support
|
| Indian council of medical research |
|
|
Primary Sponsor
|
| Name |
Indian Council of Medical Research |
| Address |
Indian council of medical research, V, Ramanlingaswami bhawan, Ansari nagar, Post Box 4911, New Delhi-110029 |
| Type of Sponsor |
Government funding agency |
|
|
Details of Secondary Sponsor
|
| Name |
Address |
| Dr Vijayakumar D K |
Amrita Institute of Medical Sciences, Ponekkara P. O., Ernakulam,Kochi, Kerala-682041, India |
|
|
Countries of Recruitment
|
India |
|
Sites of Study
|
| No of Sites = 1 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Pavithran K |
Amrita Institute of Medical Sciences |
Room No.2, Department of Medical Oncology, Amrita Institute of Medical Sciences
Ponekkara P. O., Ernakulam,Kochi, Kerala-682041, India
Ernakulam
KERALA |
9895367090
drkpavithran@gmail.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| Institutional Ethics Committee, Amrita Institute of Medical Sciences, Kochi |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: C50||Malignant neoplasm of breast, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
Low dose chemotherapy drug |
A)Trial Objective 1:
Interventional Arm: Capecitabine 500 mg x Bid per oral for 2 weeks; Cyclophosphamide 50 mg x Bid per oral for 2 weeks followed by Standard of care for triple-negative and luminal B/Her2-ve breast cancer patients
B)Trial Objective 2
Based on the objective two results, patients are categorized into responders and non-responders. Further, a non-randomized pilot study will be conducted to validate the cut-off values.
Interventional Arm: Pembrolizumab 1 mg/Kg along with Standard of care neoadjuvant chemotherapy for triple-negative and luminal B/Her2-ve breast cancer patients in both responders and non-responders.
|
| Comparator Agent |
Standard of care neoadjuvant chemotherapy |
A)Trial Objective 1:
As it is a non-randomized single-arm trial to evaluate the cut-off values to assess the tumor microenvironment response there is no comparator.
B)Trial Objective 2
Control Arm: Patient who received neoadjuvant standard of care intravenous chemotherapy in objective-2 will be consider for comparison |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
70.00 Year(s) |
| Gender |
Female |
| Details |
1. Women aged 18 and above with Breast Cancer of the subtypes Luminal B Her2-ve and TNBC
2. Women with advanced stages of Luminal B Her2-ve and TNBC that are inoperable but non-metastatic
3. Women with Luminal B Her-ve and TNBC that are eligible for NACT
|
|
| ExclusionCriteria |
| Details |
Exclusion Criteria:
1. Women with early-stage Luminal B Her-ve and TNBC tumors that are taken up for primary surgery will be excluded
2. Women with Luminal B tumors that are HER2 positive will be excluded
3. Women with Luminal A tumors will be excluded
4. Women with the above subtypes of BC having HIV, HCV, and HBV infections will be excluded from the study
5. Women undergoing treatment for BC or any other types of cancer will be excluded
6. Women with any other cancers will be excluded |
|
|
Method of Generating Random Sequence
|
Not Applicable |
|
Method of Concealment
|
Not Applicable |
|
Blinding/Masking
|
Open Label |
|
Primary Outcome
|
| Outcome |
TimePoints |
| Pathological complete response assessed by histopathology. |
Baseline to end of surgery |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
Progression free survival at 3 years
Overall survival at 5 years
New biomarkers for screening of tumour microenvironment
|
4 to 6 months |
|
|
Target Sample Size
|
Total Sample Size="50"
Sample Size from India="50"
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)
|
21/05/2024 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="3"
Months="0"
Days="0" |
|
Recruitment Status of Trial (Global)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Open to Recruitment |
|
Publication Details
|
N/A |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - YES
- What data in particular will be shared?
Response - Individual participant data that underlie the results reported in this article, after de-identification (text, tables, figures, and appendices).
- What additional supporting information will be shared?
Response - Study Protocol
Response - Statistical Analysis Plan
Response - Clinical Study Report
- Who will be able to view these files?
Response - Researchers whose proposed use of the data has been approved by an independent review committee identified for this purpose.
- For what types of analyses will this data be available?
Response - For individual participant data meta-analysis.
- By what mechanism will data be made available?
Response - Proposals should be directed to [pavithrank@aims.amrita.edu].
- For how long will this data be available start date provided 01-03-2028 and end date provided 01-03-2031?
Response - Beginning 9 months and ending 36 months following article publication.
- Any URL or additional information regarding plan/policy for sharing IPD?
Additional Information - NIL
|
|
Brief Summary
|
This study is a non-randomized open-label, single-centre trial. Immuno-suppressive-tumor-microenvironment (TME) is responsible for poor clinical response to cancer immunotherapy. Our study found that depleting MDSCs and repolarizing M2-macrophages-to-M1, enhance infiltration of lymphocytes in the TME, leading to excellent tumor control in animal models. Further, our Breast cancer TME profiling in humans revealed the association between MDSCs and PD1hi-exhausted T-cells. Overcoming TME immunosuppression is critical for improved clinical outcomes, especially for immunotherapy of difficult-to-treat breast cancers like Luminal B-Her2-ve and Triple-negative breast cancer (TNBC). Though the significance of PD-L1/CTLA4 expression in cancer is known, the critical roles of MDSCs, N2 neutrophils, regulatory-B, -DCs, and -NK cells in different BC subtypes are unknown. The impact of metronomic anti-TME therapy for improving low-dose-ICB response in TNBC is also unknown. This study plans to examine whether overcoming immune-suppressive TME using metronomic-chemotherapy and TME-based patient stratification can improve the therapeutic outcome in response to low-dose-ICB in breast cancer subtypes with poor prognosis. This approach will be safer, affordable, and more efficacious. The primary outcomes expected are, 1. A novel anti-TME approach to sensitize Luminal B-Her2-ve and TNBC patients to low-dose, affordable, and safer ICB; 2. Utility of anti-TME therapy for improving prognostication of Luminal-B/Her2-ve Breast cancer subtype. 3. High-resolution single-cell data on metronomic anti-TME therapy in breast cancer. |