| CTRI Number |
CTRI/2011/05/001748 [Registered on: 19/05/2011] Trial Registered Prospectively |
| Last Modified On: |
16/12/2011 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
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Type of Study
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Biological |
| Study Design |
Randomized, Parallel Group, Active Controlled Trial |
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Public Title of Study
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A clinical study to assess the effect of Lupin’s Filgrastim as compared to
Neupogen®(Amgen) administered after chemotherapy to prvent Neutropenia caused by chemotharapy in patients with non-myeloid malignancies
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Scientific Title of Study
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An open-label, multi-center, randomized, active controlled, comparative, phase III clinical study to assess efficacy and safety of Lupin’s Filgrastim versus Neupogen® as an adjunct to chemotherapy for prevention of neutropenia in patients with non-myeloid malignancies |
| Trial Acronym |
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Secondary IDs if Any
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| Secondary ID |
Identifier |
| LRP/GCSF/2010/001 |
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
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| Name |
Dr Rajesh Kumawat |
| Designation |
Associate Director and Head, Clinical Research Unit |
| Affiliation |
To Lupin Ltd |
| Address |
Novel Drug Discovery and Development (NDDD)
Lupin Limited (Lupin Research Park)
46A/47A, Village Nande, Mulshi taluka, Pune
Pune
MAHARASHTRA
411042
India |
| Phone |
66749100 |
| Fax |
66749560 |
| Email |
rajeshkumawat@lupinpharma.com |
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Details of Contact Person
Public Query
|
| Name |
Dr Neelam Kardekar |
| Designation |
Research Scientist |
| Affiliation |
Lupin Ltd |
| Address |
Novel Drug Discovery and Development (NDDD)
Lupin Limited (Lupin Research Park)
46A/47A, Village Nande, Mulshi taluka, Pune
Pune
MAHARASHTRA
411042
India |
| Phone |
66749000 |
| Fax |
66749560 |
| Email |
neelamkardekar@lupinpharma.com |
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Source of Monetary or Material Support
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| LUPIN LIMITED BIOTECHNOLOGY DIVISION |
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Primary Sponsor
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| Name |
LUPIN LIMITED BIOTECHNOLOGY DIVISION |
| Address |
Gat No: 1156, Village Ghotawade,
Mulshi Taluka, Pune. Pin: 411042.
Maharashtra, (India)
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| Type of Sponsor |
Pharmaceutical industry-Indian |
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Details of Secondary Sponsor
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Countries of Recruitment
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India |
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Sites of Study
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| No of Sites = 9 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Naresh Somani |
Bhagwan Mahaveer cancer hospital & Research centre |
Clinical Trial Department, Upper Ground Floor, Bhagwan Mahaveer Cancer Hospital & Research Centre, JLN marg, Malviya nagar, Jaipur_302017
Jaipur
RAJASTHAN |
0141-2700107
0141-2702021
drsomani@somexresearch.com |
| Dr Anand Pathak |
Cancer Care Clinic & Hospital |
Cancer Care Clinic & Hosiptal, Clinical Research, 5th floor, Vasant Shula Tower,Dhantoli, Nagpur
Nagpur
MAHARASHTRA |
0712-2430465
0712-2461565
jueely1194@yahoo.co.in |
| DrRajnish Vasant Nagarkar |
Curie Manavata Cancer center |
Clinical Research department, Curie Manavata Cancer center, Opp. Mahamarg Bus Stand , Mumbai Naka , Nashik , Maharashtra – 422 004.
Nashik
MAHARASHTRA |
0253-2592666
0253-2594866
drraj@manavatacancercentre.com |
| DrAshish Kaushal |
HCG- Medisurge Hospital |
Research and Development, Mithakhali 6 Road, Ellisbridge, Ahmedabad 380006
Ahmadabad
GUJARAT |
079-40010101
079-40010103
drashish4@yahoo.co.in |
| DrLokeshwar Nilesh Madhukar |
Kashyap Nurshing Home |
Kashyap Nurshing Home,Clinical Research Room, Imperical Mahal, 3rd floor, Khodadnd circle, Dadar T.T.; Mumbai400014
Mumbai
MAHARASHTRA |
022-24128020
nileshlok@yahoo.com |
| Dr Linu Abraham Jacob |
Kidwai Memorial Institute of Oncology |
Project room, OPD block, Dr.M.H. Marigowda road, Bangalore-560029
Bangalore
KARNATAKA |
080-26571122
kmiolinu@gmail.com |
| Dr Unmesh Takalkar |
Kodlikeri Memorial Hospital |
Manjeet Nagar,Opp. Akashwani,Jalna Road,Aurangabad - 431 005,Maharashtra, India.
Aurangabad
MAHARASHTRA |
0240-2335751
0240-2359279
unmesh_3@sancharnet.in |
| Dr Sharad Shankar Desai |
Mahatma Gandhi Cancer Hospital |
Deapartment of Surgical Oncology, Mahatma Gandhi Cancer Hospital,Near Gulabrao Patil Homeopathic Medical college, Zaribag; MIRAJ-416410 (Maharashtra)
Sangli
MAHARASHTRA |
0233-2211122
drsharaddesai@gmail.com |
| DrSShanmuga Kumar |
Rajeev Gandhi govt. General hospital |
The Head of Dept.- Radiation Onchology, Park Town, Opp. Central Railway station, Chennai 03
Chennai
TAMIL NADU |
04426571122
vidyaclinical@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 |
| Aunthentic EC |
Submittted/Under Review |
| ETHICS COMMITTEE KODLIKERI MEMORIAL HOSPITAL AND CIIGMA HOSPITAL. |
Approved |
| Ethics Committee, Bhagwan Mahaveer cancer hospital & Research centre |
Approved |
| Global Health Concern Ethics Committee |
Approved |
| HCG- Medisurge EC |
Approved |
| Mysore Clinical Research Ethics Committee |
Approved |
| Noble hospital, Institutional Ethics committee |
Approved |
| Professional Ethics Committee, Manavata Clinical Research Institute |
Approved |
| Rajeev Gandhi govt. General hospital Ethics Committee |
Approved |
| Sandeep Medical Independent Ethics Committee |
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 |
Chemotherapy Induced neutropenia, |
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Intervention / Comparator Agent
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| Type |
Name |
Details |
| Intervention |
Lupins Filgrastim-Granulocyte colony stimulating factor(GCSF) |
Dose: 5 µg/kg/day
Duration: 5-14 days for 2 chemotherapy cycles Frequency: Once a day
Mode of administration: Subcutaneous |
| Comparator Agent |
Neupogen®-Granulocyte colony stimulating factor(GCSF)-Filgrastim of Amegen and marketed by Roche India |
Dose: 5 µg/kg/day
Duration: 5-14 days for 2 chemotherapy cycles Frequency: Once a day
Mode of administration: Subcutaneous |
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Inclusion Criteria
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| Age From |
18.00 Year(s) |
| Age To |
65.00 Year(s) |
| Gender |
Both |
| Details |
1. Patients must be able and willing to give written informed consent prior to any study-related procedures.
2. Male or non-pregnant / non-lactating female patients between 18-65 years of age
3. Patients with histologically or cytologically confirmed non-myeloid malignancy
4. Patients planned to have myelosuppressive chemotherapy regimen that consist at least one chemotherapeutic agent from docetaxel, doxorubicin or paclitaxel.
5. Patients who have not received myelosuppressive chemotherapy within last 12 months of screening.
6. Patients with baseline ANC of ¡Ý 1 x 109/L and platelet count ¡Ý 100 x 109/L.
7. Patients with adequate hepatic and renal function [defined as Alkaline Phosphatase ¡Ü 5 X Upper limits of normal (ULN), serum SGOT and SGPT ¡Ü 2.5 X ULN (¡Ü 5 X ULN for patient with liver involvement) , Total bilirubin ¡Ü 1.5 X ULN and Creatinine ¡Ü 1.5 X ULN of the reference range at the screening assessment]
8. Patients with ECOG Performance status of 0 or 1
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| ExclusionCriteria |
| Details |
1. Patients with history of hypersensitivity to study drugs, components or similar products.
2. Patients with myeloid malignancies and myelodysplasia
3. Patients currently receiving radiation therapy or have completed radiation therapy within 4 weeks before study entry
4. Patients with prior bone marrow or stem cell transplantation.
5. Patients with chronic use of oral corticosteroids. (Except ¡Ü 20 mg/day dose of prednisolone).
6. Patients with underlying neuropathy of Grade 2 or higher.
7. Patients with history of systemic antibiotic use within 72 hours prior to chemotherapy. [However if patient is receiving antibiotics during screening, then chemotherapy can be started after 72 hours of last antibiotic dose.
8. Patients with any active infection which may require systemic antimicrobial therapy during the study.
9. Patients who have received hematopoietic growth factors (e.g. G-CSF, peg-G-CSF, erythropoietin) or cytokines (e.g. interleukins, interferons) within last 1 month of screening.
10. Known cases of HIV or HBV or HCV seropositive patients.
11. Known cases of Sickle Cell Anemia.
12. Patients with radiographic evidence of active pulmonary infections and/or recent history of pneumonia within 1 month of screening.
13. Patients with clinically evident splenomegaly confirmed subsequently by ultrasonography.
14. Patients with any other clinically significant disease(s) which, in the opinion of the investigator, could compromise the patient¡¯s involvement in the study or overall interpretation of the data.
15. Alcoholic or drug abuse patients.
16. Patients who have participated in another therapeutic clinical study within the past 30 days prior to screening, or are likely to simultaneously participate in another therapeutic clinical study.
17. Patients who are doubtful to comply with study procedures for mental, psychological or social reasons.
18. Women of child-bearing potential & all men who are not willing to follow a reliable & effective contraceptive measure during the course of the study & at least 1 month after the last visit.
19. Patients with Congestive Heart Failure Class III/IV as per NYHA Classification.
20. LVEF 50 % , except patients receiving doxorubicin containing Chemotherapy, wherein LVEF 55 %
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Method of Generating Random Sequence
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Computer generated randomization |
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Method of Concealment
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Centralized |
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Blinding/Masking
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Open Label |
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Primary Outcome
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| Outcome |
TimePoints |
| • Duration of severe neutropenia [ANC 0.5 x 109/L] in cycle 1 of chemotherapy |
Day 1, 2, 4 to 10, 15, 21(Cycle 1) |
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Secondary Outcome
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| Outcome |
TimePoints |
| assement of the neutropenia observed in the study with respect to DSN in cyecle 2, percentage of patients with neutrpoenia in the study, depth of ANC Nadir, time to ANC recovery |
Day 1, 2, 4 to 10, 15, 21(Cycle 2) |
| Incidence of Febrile Neutropenia (FN)by cycle and across the cycles, duration of FN, Rate of the hospitalization due to FN, percentage of the patients requiring system antibiotic to treat FN by cycle and acrros the cycle |
In both the cycles, day 1 to day 21 |
Safety:
• Adverse event (AE) assessment (as per NCI CTCAE Ver.4.0)
• Rate of discontinuations (proportion of patients who discontinue study treatment due to adverse events)
• Clinically significant Changes in laboratory parameters and physical examinations.
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At every patient visit in the study |
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Target Sample Size
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Total Sample Size="98"
Sample Size from India="98"
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
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Phase 3 |
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Date of First Enrollment (India)
|
09/06/2011 |
| 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 |
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Estimated Duration of Trial
|
Years="0"
Months="8"
Days="0" |
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Recruitment Status of Trial (Global)
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Not Applicable |
| Recruitment Status of Trial (India) |
Not Yet Recruiting |
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Publication Details
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Individual Participant Data (IPD) Sharing Statement
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Will individual participant data (IPD) be shared publicly (including data dictionaries)?
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Brief Summary
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Filgrastim is a human granulocyte colony-stimulating factor (G-CSF) produced by recombinant DNA technology. Filgrastim was initially used as an adjunct to chemotherapy for reducing risk of neutropenia, one of the major adverse events of cancer chemotherapy. Its use has led to reduced infections and hospital admissions for patients with cancer.
Lupin Limited, India has developed a biosimilar Filgrastim for the prevention of chemotherapy induced neutropenia in patients undergoing chemotherapy. As with other biosimilar products previously developed by other manufacturers, Lupin Limited intends to evaluate the efficacy and safety of its formulation and compare the same with existing Filgrastim formulation, Neupogen® (marketed by Roche India) to assess clinical equivalence.
This is an open-label, multi-center, randomized, active-controlled, two-arm parallel study to assess the efficacy, safety and tolerability of biosimilar Filgrastim (manufactured by Lupin Limited, India) given subcutaneously as compared to Neupogen® (Filgrastim marketed by Roche India).
· The total duration of the study(Per patient) will be approximately 42 ± 3 days.
· The study consists of pre-study or screening period of maximum 2 days.
- Eligible patients will be randomized to receive either Lupin’s Filgrastim or Neupogen® starting after 24 hours of chemotherapy for 2 chemotherapy cycles (of maximum 21 days each).
- Efficacy and safety assessments will be conducted on different days
Study Hypothesis:
Primary outcome of the study is Duration of severe neutrpenia(DSN) in cycle 1
Equivalence of biosimilar Filgrastim and Neupogen® will be assessed based on the per proptocol(PP) set, using the ANCOVA model to calculate a two-sided 95% confidence interval for “Test product (Lupin’s Filgrastim) minus Neupogen®”. Equivalence to be concluded if this confidence interval lay entirely within the equivalence rage [−1 day, +1 day] |