| CTRI Number |
CTRI/2015/05/005789 [Registered on: 20/05/2015] Trial Registered Prospectively |
| Last Modified On: |
25/10/2021 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug
Biological |
| Study Design |
Single Arm Study |
|
Public Title of Study
|
A Study of Trastuzumab in combination with chemotherapy in early Breast Cancer |
|
Scientific Title of Study
|
AN INDIAN MULTICENTRIC OPEN LABEL PROSPECTIVE PHASE IV STUDY TO EVALUATE SAFETY AND EFFICACY OF TRASTUZUMAB IN HER2 POSITIVE, NODE POSITIVE OR HIGH RISK NODE NEGATIVE BREAST CANCER AS PART OF A TREATMENT REGIMEN CONSISTING OF DOXORUBICIN, CYCLOPHOSPHAMIDE, WITH EITHER DOCETAXEL OR PACLITAXEL(AC→TH) OR DOCETAXEL AND CARBOPLATIN (TCH) |
| Trial Acronym |
|
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| ML28714 Version 1.0 dated 29Jul2013 |
Protocol Number |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr D C Doval |
| Designation |
Medical Oncologist |
| Affiliation |
Rajiv Gandhi Cancer Institute & Research Centre |
| Address |
Sector 5
Rohini
New Delhi
DELHI
110085
India |
| Phone |
011-47022428 |
| Fax |
011-27051037 |
| Email |
dcdoval@gmail.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Binay Swarup |
| Designation |
Associate Director-Medical Affairs |
| Affiliation |
Roche Products (India) Pvt. Ltd. |
| Address |
1503, 15th Floor, "The Capital"
Bandra Kurla Complex, Bandra (East)
Mumbai
MAHARASHTRA
400 051
India |
| Phone |
02233941414 |
| Fax |
02233941054 |
| Email |
binay.swarup@roche.com |
|
Details of Contact Person
Public Query
Modification(s)
|
| Name |
Priyanka Bhattacharya |
| Designation |
Associate Director-Clinical Operations |
| Affiliation |
Roche Products (India) Pvt. Ltd. |
| Address |
146-B, 166 A, Unit No. 7, 8, 9
8th Floor, R City Office, R City Mall
Lal Bahadur Shastri Marg
Ghatkopar,
Mumbai
MAHARASHTRA
400 086
India |
| Phone |
022-33941476 |
| Fax |
022-33941054 |
| Email |
priyanka.bhattacharya@roche.com |
|
|
Source of Monetary or Material Support
|
| Roche Products (India) Pvt. Ltd.
1503, 15th Floor, "The Capital"
Bandra Kurla Complex, Bandra (East)
Mumbai 400 051 |
|
Primary Sponsor
Modification(s)
|
| Name |
Roche Products India Pvt Ltd |
| Address |
146-B, 166 A, Unit No. 7, 8, 9
8th Floor, R City Office, R City Mall
Lal Bahadur Shastri Marg
Ghatkopar, Mumbai - 400 086
Maharashtra |
| Type of Sponsor |
Pharmaceutical industry-Indian |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
India |
Sites of Study
Modification(s)
|
| No of Sites = 6 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Arun Seshachalam |
Dr. GVN Cancer Institute |
Dept. Of Oncology, Room No. 46, Singarathope, Trichy-62008, Tamil Nadu
Tiruchirappalli
TAMIL NADU
Tiruchirappalli
TAMIL NADU |
0431-2700712
0431-4010000
arunonco@gmail.com |
| Dr Shona Nag |
Jehangir Clinical Development Centre Private Limited |
Jehangir Hospital
Premises, 32, Sassoon
Road, Pune 411001
Pune
MAHARASHTRA |
9371072441
shonanag3@gmail.com |
| Dr Poonam Patil |
Manipal Hospital |
Rustom Bagh,
HAL Airport Road,
Bangalore- 560017
Bangalore
KARNATAKA |
9945687185
poonampatil@yahoo.com |
| Dr Meenu Walia |
Max Super Speciality Hospital (A unit of Balaji Medical and Diagnostic Research Centre) |
108-A, Indraprastha Ext., Patparganj, New Delhi – 110092
New Delhi
DELHI |
9818994001
1122235563
meenu.Walia@maxhealthcare.com |
| Dr Dinesh Chandra Doval |
Rajiv Gandhi Cancer Institute and Research Center |
Sector-5, Rohini,
New Delhi - 110085, India
New Delhi
DELHI |
01147022252
dcdoval@gmail.com |
| Dr Nikhil Ghadyalpatil |
Yashoda Hospitals |
Raj Bhavan Road, Somajiguda, Hyderabad 500082, Telangana Stste, India
Hyderabad
ANDHRA PRADESH |
8008037474
04023414613
nikhilghadyalpatil@gmail.com |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 6 |
| Name of Committee |
Approval Status |
| Ethics Committee of Manipal Hospitals |
Approved |
| Ethics Committee, JCDC |
Approved |
| Institutional Ethics Committee, Dr. GVN Cancer Institute |
Approved |
| Institutional Ethics Committee, Max Super Specialty Hospital (A unit of Balaji Medical & Diagnostic Research Centre) |
Approved |
| Institutional Ethics Committee, Yashoda Academy of Medical Education & Research, Yashoda Group of Hospitals |
Approved |
| Institutional Review Board, Rajiv Gandhi Cancer Institute & Research Centre |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
Health Condition / Problems Studied
Modification(s)
|
| Health Type |
Condition |
| Patients |
HER2 POSITIVE, NODE POSITIVE OR HIGH RISK NODE NEGATIVE BREAST CANCER , (1) ICD-10 Condition: C50||Malignant neoplasm of breast, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Comparator Agent |
NIL |
NIL |
| Intervention |
Trastuzumab
Docetaxel / Paclitaxel
Doxorubicin, Cyclophosphamide
Carboplatin |
1. AC-TH regimen:
• Every 3 weeks for 4 cycles, patients in the ACTH regimen will be receiving 60
mg/m2 doxorubicin as a 5 to15 minute I.V. bolus injection followed by 600
mg/m2 cyclophosphamide as a 5 to 60 minute I.V. bolus injection.
• On Day 1 of Cycle 5, 4-mg/kg Trastuzumab loading dose will be administered as
a 90 minute I.V. infusion as a weekly regimen OR 8-mg/kg Trastuzumab loading
dose will be administered as a 90-minute I.V. infusion as a 3 weekly regimen at
Investigator’s discretion.
• If weekly regimen of Trastuzumab is selected, on Day 8 of Cycle 5, 2 mg/kg
Trastuzumab will be administered as a 30-minute I.V. infusion and 2mg/ kg
every week as a weekly regimen will be given OR beginning on Day 1 of Cycle
6, Trastuzumab 6 mg/kg will be administered as a 30-minute I.V. infusion every
3 weeks as a 3 weekly regimen for four cycles.
• Docetaxel 100 mg/m2 or Paclitaxel 175 mg/m2 (at investigator’s discretion) will
be administered as a 1 hour I.V. infusion every 3 weeks for four cycles,
beginning on Day 1 of Cycle 5 and continued for up to Cycle 8.
• Three weeks after the last treatment with docetaxel/paclitaxel (i.e., on Day 1 of
Cycle 9), 6 mg/kg Trastuzumab will be administered as a 30-minute I.V. infusion
every 3 weeks. Trastuzumab treatment will be continued up to cycle 22
(completing a total 52 week trastuzumab therapy).
2. TCH regimen:
• Trastuzumab will be given intravenously at a dose of 4 mg/kg loading dose
administered as a 90 minute I.V. infusion followed by 2 mg/kg administered as a
30 minute I.V. infusion weekly as a weekly regimen or 8-mg/kg Trastuzumab
loading dose administered as a 90 minute I.V. infusion followed by 6 mg/kg
administered as a 30 minute I.V. infusion 3 weekly as a 3 weekly regimen during
chemotherapy from cycle 1 to 6 at Investigator’s discretion.
• Every 3 weeks for six cycles, patients in the TCH regimen will be receiving 75
mg/m2 docetaxel as a 60-minute I.V. bolus injection followed by AUC 6 x (GFR
+ 25) carboplatin as a 30 to 60 minute I.V. bolus injection.
• After completion of chemotherapy, Trastuzumab will be administered at a dose
of 6 mg/kg every 3 weeks up to cycle 18 (completing total 52 week trastuzumab
therapy)
|
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
99.00 Year(s) |
| Gender |
Female |
| Details |
Patients must meet the following criteria for study entry:
•Able and willing to give written informed consent and comply with the requirements of the study protocol.
•Adult female patients, ≥18 years of age
•Histologically confirmed early invasive HER2 positive, node positive or high risk node negative breast cancer with no evidence of residual, locally recurrent or metastatic disease and defined as clinical stage I to IIIA that is eligible for adjuvant treatment with Trastuzumab
•Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
•HER2 over-expression/amplification defined as either IHC3+, or IHC2+ and FISH-positive as determined in a central laboratory
•At time of starting Trastuzumab therapy, Left ventricular ejection fraction (LVEF) measured by echocardiography
•Screening left ventricular ejection fraction (LVEF) ≥ 55%
•Adequate bone marrow, renal, and hepatic function
•Agreement to use an adequate, non-hormonal means of contraception by women of childbearing potential |
|
| ExclusionCriteria |
| Details |
Patients who meet any of the following criteria will be excluded from study entry:
•Any contraindication to Trastuzumab
•Previous adjuvant breast cancer treatment with an approved or investigational anti HER2 agent
•History of other malignancy, except for curatively treated carcinoma in situ of the cervix or basal cell carcinoma and patients with other curatively treated malignancies who have been disease-free for at least 5 years
•Past history of ductal carcinoma in situ and/or lobular carcinoma that has been treated with any systemic therapy or with radiation therapy to the ipsilateral breast where the invasive cancer subsequently develops
•Locally advanced (stage IIIB and IIIC) and Metastatic disease (stage IV)
•Clinically relevant cardiovascular disorder or disease
•Uncontrolled hypertension, or history of hypertensive crisis or hypertensive encephalopathy
•History of severe allergic or immunological reactions, e.g. difficult to control asthma
•Pregnant or lactating women |
|
|
Method of Generating Random Sequence
|
Not Applicable |
|
Method of Concealment
|
Not Applicable |
|
Blinding/Masking
|
Not Applicable |
|
Primary Outcome
|
| Outcome |
TimePoints |
| To evaluate the safety of Trastuzumab for the treatment of HER2-positive node positive or high risk node negative breast cancer patients with regimen consisting of doxorubicin and cyclophosphamide followed by either paclitaxel or docetaxel (AC→TH) or a regimen consisting of docetaxel and carboplatin (TCH) in Indian population. |
Assessed every 3 months (after every 4th cycle) until disease progression |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
To determine the disease free survival (DFS); To determine the overall survival (OS).
|
Assessed every 3 months (after every 4th cycle) until disease progression |
|
|
Target Sample Size
|
Total Sample Size="109"
Sample Size from India="109"
Final Enrollment numbers achieved (Total)= "110"
Final Enrollment numbers achieved (India)="110" |
|
Phase of Trial
|
Phase 4 |
Date of First Enrollment (India)
Modification(s)
|
18/08/2016 |
| Date of Study Completion (India) |
24/06/2021 |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Date Missing |
|
Estimated Duration of Trial
|
Years="4"
Months="6"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Completed |
|
Publication Details
|
|
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
|
|
Brief Summary
|
India would recruit 109 patients in the study. India will have the first patient enrolled in 20-May-2015.This Open label study is being conducted to evaluate the safety and efficacy of trastuzumab in Her2 positive, node positive or high risk node negative breast cancer as part of a treatment regimen consisting of Doxorubicin, Cyclophosphamide, with either Docetaxel or Paclitaxel(ac->th) or Docetaxel and Carboplatin (TCH).The anticipated time on study treatment is until disease progression. |