CTRI

FULL DETAILS (Read-only) -> Click Here to Create PDF for Current Dataset of Trial

CTRI Number

CTRI/2013/04/003549 [Registered on: 12/04/2013] Trial Registered Prospectively

Last Modified On:

20/09/2017

Post Graduate Thesis

Type of Trial

Interventional

Type of Study

Drug
Biological

Study Design

Randomized, Parallel Group, Active Controlled Trial

Public Title of Study

A clinical trial to study the effects of two drugs, R-TPR-016 and HerceptinÂ® in patients with Metastatic HER2-Overexpressing Breast Cancer

Scientific Title of Study

Prospective, multi-centre, randomized, open-label, twoarm, parallel group, active-control, comparative clinical study to evaluate efficacy, safety and pharmacokinetics of R-TPR-016/ HerceptinÂ® when given intravenously in patients with Metastatic HER2-Overexpressing Breast Cancer

Trial Acronym

Secondary IDs if Any

Secondary ID	Identifier
RLS/TP/2011/05, Version 03, Dated 13th Dec 2012	Protocol Number

Details of Principal Investigator or overall Trial Coordinator (multi-center study)

Name	Dr Parvez Kosgi
Designation	Head RLS clinical Trial
Affiliation	Reliance Life Sciences Pvt. Ltd
Address	Dhirubhai Ambani Life Sciences Centre R-282 TTC Area of MIDC Rabale Navi Mumbai Thane MAHARASHTRA 400701 India
Phone	02240678000
Fax	02240678299
Email	parvez.kosgi@relbio.com

Details of Contact Person
Scientific Query
Modification(s)

Name	Dr Sashank Deoghare
Designation	Medical Monitor
Affiliation	Reliance Life Sciences Pvt.Ltd
Address	Reliance Life Sciences Plot R-282, Thane Belapur Road, Rabale, Navi Mumbai 400 701 Thane MAHARASHTRA 400701 India
Phone	02267678287
Fax
Email	sashank.deoghare@relbio.com

Details of Contact Person
Public Query

Name	Dr Parvez Kosgi
Designation	Head RLS clinical Trial
Affiliation	Reliance Life Sciences Pvt.Ltd
Address	Dhirubhai Ambani Life Sciences Centre R-282 TTC Area of MIDC Rabale Navi Mumbai Thane MAHARASHTRA 400701 India
Phone	0224067000
Fax	02240678299
Email	parvez.kosgi@relbio.com

Source of Monetary or Material Support

Reliance Life sciences Pvt. Ltd. Dhirubhai Ambani Life Sciences Centre Plot R-282, TTC Area of MIDC Thane Belapur Road, Rabale, Navi Mumbai 400 701. India

Primary Sponsor

Name	Reliance Life sciences Pvt Ltd
Address	Dhirubhai Ambani Life Sciences Centre Plot R-282, TTC Area of MIDC, Thane Belapur Road Rabale, Navi Mumbai 400 701 India
Type of Sponsor	Pharmaceutical industry-Indian

Details of Secondary Sponsor

Name	Address
NIL	NIL

Countries of Recruitment

India

Sites of Study
Modification(s)

No of Sites = 20
Name of Principal Investigator	Name of Site	Site Address	Phone/Fax/Email
Dr DiptiRani Samantha Medical Oncologist	Acharya Harihar Regional Cancer Centre	Acharya Harihar Regional Cancer Centre,Medical Road, managalbag, Cuttack-753007 Cuttack ORISSA	09437032728 diptiranisamanta@rediffmail.com
Dr M R Bardia Director	Acharya Tulsi Regional Cancer Institute & Research Centre	S P Medical College & A G of Hospitals Bikaner-334003 Bikaner RAJASTHAN	0151-2226329 directorrrccbkn@gmail.com
Dr J B sharma Hon Sr Consultant	Action Cancer Hospital	A-4, Paschim Vihar, Room No 806, Clinical Research Dept, New Delhi-110063 New Delhi DELHI	9811167505 Dr_sharmajb@rediffmail.com
Dr Anand Pathak Medical Oncologist	Cancer Care Clinic & Hospital	5th floor Vasant Sheela tower Dhantoli, Nagpur-440012 Nagpur MAHARASHTRA	07122430465 jueely1194@yahoo.co.in
Dr Rajnish Nagarkar Medical Oncologist	Curie Manavta Cancer Centre, Nashik	Curie ManavataCancer Institute, Opp Mahamarg Bus stand, Mumbai-Naka,Nashik-422004 Nashik MAHARASHTRA	9823061929 drraj@manavatacancercentre.com
Dr Rajesh Kumar Grover Director CEO	Delhi State Cancer Institute	Dilshad Garden, Delhi-110095 East DELHI	01122135700 dsci.delhi@yahoo.co.in
Dr Jaiprakash Baraskar Surgical Oncologist	Dr. Baraskar Hospital and Cancer Care Center	Room 05 3rd Floor 278 Central Bazaar Road Ramdaspeth Nagpur 440010 Nagpur MAHARASHTRA	07122420050 jpcancercare2005@yahoo.co.in
Dr A Rajkumar Medical Oncologist	G. Kuppuswamy Naidu Memorial Hospital	G. Kuppuswamy Naidu Memorial Hospital, Department of Medical Oncology, Pappanaickenpalyam, Coimbatore Coimbatore TAMIL NADU	04222245000 draprince@yahoo.com
Dr Harsha Panchal Medical Oncologist	Gujarat Cancer and Research Institute	New Civil Hospital Campus, Asarwa, Ahmedabad-380016 Ahmadabad GUJARAT	07922688419 drharshapanchal@gmail.com
Dr Ashish Kaushal Medical Oncologist	HCG Cancer Centre	Sola Science City Road Near Sola Bridge S.G. Highway Ahmadabad- 380060 Ahmadabad GUJARAT	09978297842 drashish4@yahoo.co.in
Dr Yathish Medical Oncologist	Karnataka cancer Hospital & Research Centre	Karnataka cancer Hospital & Research Centre, #99 Jharakabande, Krsihananda Nagar, nadini Layout Post, Bangalore 560096 Bangalore KARNATAKA	08023574160 dryathish@hotmail.com
Dr Krishna Prasad Medical Oncologist	Kasturba Medical College Hospital	Department of Medical Oncology, Attavar, Mangalore -575001 Dakshina Kannada KARNATAKA	0824445858 drkrishnaprasad@hotmail.com
Dr Minish Jain Medical Oncologist	KEM Hospital	K. E. M. Hospital Day Care Centre 3rd Floor Banoo Modliar Road Rasta Peth Pune-411011 Pune MAHARASHTRA	9823133390 drminishjain@yahoo.co.in
Dr Unmesh Takalkar Oncosurgeon	Kodlikeri Memorial Hospital	8 Manjeet Nagar Opp. Akashwani Jalna Road Aurangabad Aurangabad MAHARASHTRA	02039841200 unmesh_3@sancharnet.in
DrSuraj Pawar	Kolhapur Cancer centre	R-S 238, Gokul Shirgaon,Opposite Mayur Petrol Pump, Karveer, Kolhapur- 416234,Maharashtra, India. Kolhapur MAHARASHTRA	02312532034 kolhapurcancercentre@gmail.com
Murali K Voonna	Mahatma Gandhi Cancer Hospital and Research Institute	A Unit of Vizag Hospital and Cancer Research Centre Pvt Ltd1/7 MVP Colony,Vishakapatnam â€“ 530017 Visakhapatnam ANDHRA PRADESH	08912551811 muralivoonna@yahoo.com
Dr Kirushna Kumar Head Oncology	Meenakshi Mission Hospital	1st Floor Department Of Medical Oncology Lake Area Melur Road Madurai 625 107 India Madurai TAMIL NADU	09787713004 drkskk@yahoo.com
Dr Tushar Patil Medical Oncologist	Sahyadri Speciality Hospital	30/C Karve Road Erandwane Pune- 411004 Pune MAHARASHTRA	09552522556 tussipats@hotmail.com
Dr Anita Ramesh Professor Medical Oncology	Shri Ramachandra medical Centre	No-1, Ramchandra Nagar, Prur, Chennai-600116 Chennai TAMIL NADU	9840758567 Anitachandra100@hotmail.com
Dr R S Arora Oncosurgeon	Sujan Surgical Cancer Hospital & Amravati Cancer Foundation	Sujan Surgical Cancer Hospital & Amravati Cancer Foundation, 52/B Shankar Nagar Main Road Amravati-444606 Amravati MAHARASHTRA	09823097573 dr_rsaroa2@rediffmail.com

Details of Ethics Committee
Modification(s)

No of Ethics Committees= 20
Name of Committee	Approval Status
Acharya Harihar Regional Cancer Centre Institutional Ethics Committee	Approved
Action Cancer Hospital ethics Committee	Approved
Amravati Ethics Committee	Approved
Delhi State Cancer Institute Institutional Ethics Committee	Approved
Ethical Review Board, Meenakshi Mission Hospital & Research Center, Madurai	Approved
Ethics Committee, Kodlikeri Memorial Hospital & CIIGMA Hospital , Aurangabad	Approved
Ethics Committtee, KEM Hospital Research Centre	Approved
GCRI/GCS Ethics Committee	Approved
HCG Multispeciality Ethics Committee	Approved
Institutional Ethics Commitee	Approved
Institutional Ethics Committee	Approved
Institutional Ethics Committee S P Medical College & A G of Hospitals	Approved
Institutional Ethics Committee,Karanataka Cancer Hospital, Bangalore	Approved
Institutional Review Board	Approved
Jasleen Hospital Ethics Commitee	Approved
Kolhapur Cancer Institutional Ethics Commitee	Approved
Manavta Clinical Research Institute	Approved
Manipal University Ethics Committee	Approved
Sahyadri Hospital Ethics Committee	Approved
Sri Ramachandra University	Approved

Regulatory Clearance Status from DCGI

Status

Approved/Obtained

Health Condition / Problems Studied

Health Type	Condition
Patients	Patients with Metastatic HER2-Overexpressing Breast Cancer ,

Intervention / Comparator Agent

Type	Name	Details
Comparator Agent	HerceptinÂ®	Dose:Loading dose is 8 mg/kg followed by 6mg/kg in subsequent cycles Frequency: Every 3 weeks, Total Duration: 25 weeks, Route of Administration: Intravenous
Intervention	R-TPR-016	Dose:Loading dose is 8 mg/kg followed by 6mg/kg in subsequent cycles Frequency: Every 3 weeks, Total Duration: 25 weeks, Route of Administration: Intravenous

Inclusion Criteria

Age From	18.00 Year(s)
Age To	65.00 Year(s)
Gender	Female
Details	2. Histologically or cytologically confirmed adenocarcinoma of the breast with locally advanced or metastatic disease that is HER2 positive as confirmed by positive fluorescence in situ hybridization (FISH) or by immunohistochemistry 3+ score. 3. Patients who have received adjuvant therapy and/or completed no more than 1 regimen of chemotherapy for metastatic disease. Any previous chemotherapy exposure should have been completed >3 weeks before randomization into the present study. 4. Eastern Cooperative Oncology Group (ECOG) performance status â‰¤2. 5. At least 1 measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria (specifically, ascites, pleural, or pericardial effusions, osteoblastic bone metastases, or carcinomatous lymphangitis of the lung cannot be the only lesion) 6. Normal laboratory tests including ANC â‰¥1.5x109/L, Platelets â‰¥100x109/L, Hemoglobin>9.0 g/dL, Serum Creatinine â‰¤ 1.5 ULN and Total bilirubin â‰¤ 1.5 mg/dL. 7. Subjects with baseline cardiac ejection fraction â‰¥ 50% by echocardiography (ECHO) or Multiple Gate Acquisition (MUGA) scan. 8. Estimated life expectancy >6 months 9. Able to understand the study procedures, the risks involved, willing to provide written Informed Consent, and able to adhere to study schedules and requirements.

ExclusionCriteria

Details

1. Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease, wound healing disorders, ulcers or bone fractures)
2. Patients with history of radiation within 4 weeks before the first cycle of chemotherapy in the study or planning radiation during the first 3 cycles of the study.
3. Previous bone marrow or stem-cell transplantation
4. Diagnosis of concurrent second malignancy or leukemia, myeloid aplasia, aplastic anemia, sickle cell disease and/or lymphoma with marrow involvement and/or known
brain metastases
5. History of chemotherapy causing delayed myelosuppression (nitrosureas, mitomycin C, etc.)
6. History of trastuzumab administration â‰¤ 21 days prior to randomization.
7. Current clinical or radiographic evidence of central nervous system (CNS) metastases.
8. History of exposure to the following cumulative doses of anthracyclines: Doxorubicin or liposomal doxorubicin 500 mg/m2; Epirubicin 900 mg/m2; Mitoxantrone 120mg/m2 and idarubicin 90 mg/m2
9. Major surgical procedure or significant traumatic injury within approximately 28 days prior to randomization or anticipation of the need for major surgery during the course
of study treatment
10. History of intolerance (including Grade 3-4 infusion reaction) or hypersensitivity to trastuzumab, murine proteins or paclitaxel
11. Serious inter-current chronic or acute illness such as pulmonary (asthma or COPD) or cardiac (NYHA class III or IV) or hepatic disease or other illness considered by the
Principal Investigator to constitute an unwarranted high risk for investigational drug treatment
12. Severe dyspnoea at rest due to complications of advanced malignancy or requiring supplementary oxygen therapy.
13. Cardiac disease that would preclude the use of doxorubicin, docetaxel and trastuzumab:
o Any documented myocardial Infarction
o Angina pectoris that requires the use of anti-angina medication
o Any history of documented congestive heart failure
o Grade 3 or Grade 4 cardiac arrhythmia
o Clinically significant valvular heart disease
o Patients with cardiomegaly on chest x-ray or ventricular hypertrophy on ECG, unless they demonstrate by MUGA scan within the past 3 months that the LVEF is â‰¥ the lower limit of normal for the radiology facility;
o LVEF below 50% within approximately 28 days prior to randomization
o Patients with poorly controlled hypertension i.e. diastolic greater than 100 mm/Hg. (Patients who are well controlled on medication are eligible for entry)
o Patients who currently receive medications (digitalis, beta-blockers, calcium channel blockers, etc) that alter cardiac conduction, if these medications are administered for cardiac arrhythmia, angina or congestive heart failure. If these medications are administered for other reasons (e.g., hypertension), the patient will be eligible.
14. Pre-existing grade 2 or greater motor or sensory neuropathy.
15. Women who are pregnant or breast-feeding or women of child bearing potential who are not using effective contraception during participation in the study and do not
agree to do so for at least 28 days after final dose of investigational product.
16. Serious underlying medical condition which could impair the ability of patient to participate in the trial (e.g. active systemic infection).
17. Subjects with known acute or chronic infection, including urinary tract infection, HIV, HBsAg, HBV, HCV at the time of screening.
18. Subject participation in another clinical trial within 30 days prior to administration of IP.
19. Any other condition which investigator feels would pose a significant hazard to subject, if IP is administered.

Method of Generating Random Sequence

Computer generated randomization

Method of Concealment

Centralized

Blinding/Masking

Open Label

Primary Outcome

Outcome	TimePoints
Efficacy will be assessed as Objective Response Rate (Complete Response and Partial Response) by RECIST 1.1 criteria at 25 weeks	25 weeks

Secondary Outcome

Outcome	TimePoints
1. To assess the disease progression free survival (PFS) rate And evaluate ORR at 52 weeks and 2 years 2. To determine single dose pharmacokinetics of R-TPR-016 and HerceptinÂ® 3. To evaluate overall survival (OS) rate at 5 years. 4. Evaluation of safety	1.ORR at 52 weeks and 2 years 2.Overall survival (OS) rate at 5 years

Target Sample Size

Total Sample Size="105"
Sample Size from India="105"
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)
Modification(s)

16/05/2013

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)
Modification(s)

Not Applicable

Recruitment Status of Trial (India)

Closed to Recruitment of Participants

Publication Details

Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?

Brief Summary
Modification(s)

This is a prospective, multi-centre, open-label, two-arm, parallel group, active-control, randomized comparative clinical study. The study will evaluate the efficacy safety and pharmacokinetics of R-TPR-016 and HerceptinÂ® in patients with Metastatic HER2-Overexpressing Breast Cancer.

The primary outcome measures was to assess the efficacy as overall response rate (Complete Response and Partial Response) assessed by RECIST 1.1 criteria at 25 weeks. 105 subject were recruited from 20 sites in India.