| CTRI Number |
CTRI/2019/09/021090 [Registered on: 06/09/2019] Trial Registered Prospectively |
| Last Modified On: |
03/11/2021 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group, Active Controlled Trial |
|
Public Title of Study
|
A Phase III Trial to Compare the Effectiveness, Safety and action of HD204 (study drug) in comparison to Avastin® in patients with Metastatic or Recurrent Non-squamous Non-small Cell Lung Cancer (cancer of the lungs)
|
|
Scientific Title of Study
|
A Randomized, Double-blind, Parallel Group, Equivalence, Multicenter Phase III Trial to Compare the Efficacy, Safety, Pharmacokinetics and Immunogenicity of HD204 to Avastin® in patients with Metastatic or Recurrent Non-squamous Non-small Cell Lung Cancer |
| Trial Acronym |
|
Secondary IDs if Any
Modification(s)
|
| Secondary ID |
Identifier |
| Protocol Amendment Version No. 4.0 dated 26-FEB-2021 |
Protocol Number |
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Modification(s)
|
| Name |
Prof Xavier Pivot |
| Designation |
Director |
| Affiliation |
Institut de Cancérologie Strasbourg Europe |
| Address |
Institut de Cancérologie Strasbourg Europe – ICANS
17, Rue Albert Calmette-BP
67033 Strasbourg
France
Email:
67033
Other |
| Phone |
|
| Fax |
|
| Email |
x.pivot@icans.eu |
|
Details of Contact Person
Scientific Query
|
| Name |
Suneela Thatte |
| Designation |
Head India Local Solutions Early Clinical Development |
| Affiliation |
IQVIA RDS India Private Limited |
| Address |
6th Floor, 194 MV Road, Near Western Express Highway Metro Station Andheri East, Mumbai
Mumbai
MAHARASHTRA
400069
India |
| Phone |
912266774242 |
| Fax |
912266774343 |
| Email |
suneela.thatte@quintiles.com |
|
Details of Contact Person
Public Query
|
| Name |
Suneela Thatte |
| Designation |
Head India Local Solutions Early Clinical Development |
| Affiliation |
IQVIA RDS India Private Limited |
| Address |
6th Floor, 194 MV Road, Near Western Express Highway Metro Station Andheri East, Mumbai
MAHARASHTRA
400069
India |
| Phone |
912266774242 |
| Fax |
912266774343 |
| Email |
suneela.thatte@quintiles.com |
|
|
Source of Monetary or Material Support
|
| Prestige BioPharma Pte Ltd
2 Science Park Drive,
Ascent Tower B, #04-13/14,
Singapore 118222
|
|
Primary Sponsor
Modification(s)
|
| Name |
Prestige BioPharma Limited |
| Address |
21 Biopolis Road, #04-24/28 Nucleos South Building, Biopolis, Singapore 138567 |
| Type of Sponsor |
Pharmaceutical industry-Global |
|
Details of Secondary Sponsor
Modification(s)
|
| Name |
Address |
| IQVIA RDS India Private Limited |
Omega, Embassy Tech Square Marathahalli - Sarjapur Outer Ring Road, Kadubeesanahalli Bangalore-560103, Karnataka India |
|
|
Countries of Recruitment
|
Belarus
Bulgaria
Croatia
Georgia
Greece
Hungary
India
Latvia
Malaysia
Philippines
Poland
Russian Federation
Serbia
Slovakia
Thailand
Turkey
Ukraine |
Sites of Study
Modification(s)
|
| No of Sites = 9 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Nirmal Raut |
Bhakti Vedanta Hospital and Research Institute |
1st Floor, Department of oncology,Srishti Complex, Bhativedanta Swami Marg, Mira Road (east)Thane, Maharashtra, India-401107
Mumbai
MAHARASHTRA |
91-9930398156
drnirmalraut@gmail.com |
| Dr Sachin Sharadchandra Hingmire |
Deenanath Mangeshkar Hospital & Research Centre |
Department of oncology, 1st Floor, Lata Mangeshkar Medical Foundation, Erandwane, Pune-411004
Pune
MAHARASHTRA |
91-9923002407
info@dmhospital.org |
| Dr Prakash Pandit |
HCG Manavata Cancer Centre |
Basement 1, OPD 2, Radiation oncology,Behind Shivang Auto, Mumbai Naka, Nashik-422002, Maharashtra, India
Nashik
MAHARASHTRA |
91-9882969969
91-253-2594866
drpandit@mcrinasik.com |
| Dr Sandip Shah |
Hemato Oncology Clinic Ahmedabad Pvt Ltd, (Vedanta institut€ of medical sciences) |
Vedanta institute of medical sciences, 1st Floor, Stadium Commerce College Road, Near Samved Hospital, Navrangpura,Ahmedabad 380009
Ahmadabad
GUJARAT |
9824041170
sandip60@yahoo.com |
| Dr Chanchal Goswami |
Medica Super Speciality |
6th, Medical Oncology dept , 127 Mukundapur, E.M.Bypass Kolkata-700099
Kolkata
WEST BENGAL |
91-9830055035
drcgoswami@gmail.com |
| Dr Jayantilal Patel |
Nirmal Hospital Private Limited |
5th Floor, Clinical Research Department,Ring Road, Surat-395002, Gujarat, India
Ahmadabad
GUJARAT |
91-9930398156
drnirmalraut@gmail.com |
| Dr Minish Jain |
Noble Hospital Pvt. Ltd |
Department clinical research annex building basement, room no. 3, 153,Magarpatta City Road, 411013
Pune
MAHARASHTRA |
02043285594
minishjain009@rediffmail.com |
| Dr Shailesh Bondarde |
S7 Clinical Research Centre Pvt.Ltd |
-27/28, besides Sai-Art printing shop, Ground Floor,S7 Clinical Research Department A wing Shatabdi Hospital, Mumbai Naka, Suyojit City centre, opp. Mahamarg bus stand, Nashik-422001
Nashik
MAHARASHTRA |
91-9822012427
shaileshbondarde1971@gmail.com |
| Dr Rajendrasingh Arora |
Sujan Surgical Cancer Hospital & Amravati Cancer Foundation |
52/B Shankar Nagar, Main Road,
Amravati-444606, Maharashtra
Amravati
MAHARASHTRA |
9823097573
07212578568
rsaroradr@gmail.com |
|
Details of Ethics Committee
Modification(s)
|
| No of Ethics Committees= 9 |
| Name of Committee |
Approval Status |
| Bhaktivedanta Hospital Ethics Committee; |
Submittted/Under Review |
| Clinical Research Ethics Committee, Medica Superspeciality Hospital |
Submittted/Under Review |
| Ethics Committee of Care Institute of Medical Sciences |
Approved |
| Institutional Ethics Committee Deenanath Mangeshkar Hospital & Research Centre Erandawane, Pune 411004 |
Submittted/Under Review |
| Institutional Ethics Committee Sujan Surgical Cancer Hospital & Amravati Cancer Foundation, 52/B Shankar Nagar, Main Road, Amravati-444606, Maharashtra |
Approved |
| Manavata Clinical Research Institute, Ethics Committee |
Approved |
| Nirmal Hospital Pvt. Ltd , Ring road , Surat-395002 |
Approved |
| Noble Hospital Institutional Ethics Committee |
Approved |
| Shatabdi Hospital Ethics Committee |
Approved |
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Regulatory Clearance Status from DCGI
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Health Condition / Problems Studied
Modification(s)
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| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: C399||Malignant neoplasm of lower respiratory tract, part unspecified, |
|
Intervention / Comparator Agent
Modification(s)
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| Type |
Name |
Details |
| Intervention |
Arm A |
HD204 (Bevacizumab-biosimilar):
Each patient will receive HD204 at a dosage of 15 mg/kg intravenous (IV) infusion
every 3 weeks on Day 1 from Cycles 1-17.
• Chemotherapy:
Each patient will be given Carboplatin AUC 6 IV every 3 weeks on Day 1 for 4 to 6
cycles as well as Paclitaxel 200 mg/m2 IV every 3 weeks on Day 1 for 4 to 6 cycles.
|
| Comparator Agent |
Arm B |
EU-Avastin® (Bevacizumab):
Each patient will receive EU-Avastin® at a dosage of 15 mg/kg intravenous (IV)
infusion every 3 weeks on Day 1 from Cycles 1-17.
• Chemotherapy:
Each patient will be given Carboplatin AUC 6 IV every 3 weeks on Day 1 for 4 to 6
cycles as well as Paclitaxel 200 mg/m2 IV every 3 weeks on Day 1 for 4 to 6 cycles.
|
|
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Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
65.00 Year(s) |
| Gender |
Both |
| Details |
1. Able and willing to give written informed consent.
2. Aged ≥ 18 years of age.
3. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1 and
life expectancy >3 months based on Investigator’s judgement.
4. Histologically confirmed metastatic Stage IV or recurrent non-squamous non-small cell lung cancer (NSCLC) that is no longer amendable to curative surgery or local therapy.
5. At least one measurable lesion according to RECIST v.1.1. as confirmed by CIR; bone-only and brain-only metastases are not allowed. Lesions previously treated with radiotherapy are non-target lesions unless clear progression was documented.
Previous results are acceptable if performed within 4 weeks prior to screening.
6. No first line treatment for metastatic or recurrent disease. Prior systemic therapy
and/or radiotherapy for locally advanced disease is permitted if completed > 6 months prior to the diagnosis of relapsing disease.
7. Tumors without EGFR mutation or ALK receptor alteration. Patients with unknown mutation status or known EGFR mutation or ALK receptor alteration may be included provided the corresponding targeted agent is not available and chemotherapy is the standard of care of the study center.
8. Adequate hematological function, defined as:
a. Platelet count: >100,000/μL without the need for transfusion in the 2 weeks
prior to Screening.
b. Prothrombin time (PT), International normalized ratio (INR) or activated partial thromboplastin time (aPTT) ≤1.5 x the upper limit of normal (ULN).
c. Absolute neutrophil count: >1,500/μL without any medical interventional treatment (ie, granulocyte-colony stimulating factors [G-CSFs] and/or herbal remedies).
d. Hemoglobin: >9 g/dL, without the need for transfusion in the 2 weeks prior to Screening.
9. Adequate hepatic function as evidenced by meeting all of the following requirements:
a. Total bilirubin: <1.5 x ULN.
b. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP): <3 x ULN.
c. If liver metastases are present, ALT or AST <5 x ULN; if liver and/or bone metastases are present ALP <5 x ULN.
10. Adequate renal function, as evidenced by meeting all of the following requirements:
a. Serum creatinine <1.5 x ULN and creatinine clearance > 50 mL/minute or estimated glomerular filtration rate (GFR) >50 mL/minute.
b. Urine dipstick for proteinuria of less than 2+ (other ways of urinalysis are also acceptable); if urine dip stick is > 2+, proteinuria must be < 2 g in 24 hours or an equivalent protein/creatinine ratio of <2000 mg/g creatinine (or < 226.0 mg/mmoL creatinine).
11. Female patients with child bearing potential (excluding women who have undergone surgical sterilization or menopause. Menopause is defined as the status where no menstrual periods continue for 1 year or more without any other medical reasons), are eligible if they have negative serum pregnancy testing within 7 days prior to first dosing and are willing to use an effective method of birth control/contraception to prevent pregnancy until 6 months after the end of study. Male patients must consent using effective method of contraception until 6 months
after the end of study.
Note: Contraceptive methods that are considered highly effective are hormonal contraceptives (contraceptive pills, hormonal implants, transdermal patches, hormonal vaginal devices, or injections with prolonged release), an intra uterine device, a double-barrier method (such as condom plus diaphragm with spermicide.
|
|
| ExclusionCriteria |
| Details |
1Diagnosisofsmallcellcarcinomaofthelungormixedtumorsincludingsmallcellcarcinoma.2Known ROS-1 positive tumor.3Tumorcavitation,tumorinvadinginto large blood vessels or close to large vessels
with high risk of bleeding,according to PI judgment.4Prior therapy with monoclonal antibodies or small molecule inhibitors against VEGF or VEGFR.5Prior systemic anticancer therapy or radiotherapy for locally advanced nsNSCLC if
completed<6 months prior to the diagnosis of relapsing disease.6Previous malignancy other than NSCLC in the last 5 yrs except for basal cell cancer of the skin or pre-invasive cancer of the cervix.7Known brain metastasis or other CNS metastasis that is either symptomatic or
untreated. Metastases that have been treated by complete resection and/or radiotherapy demonstrating stability or improvement are not an exclusion criterion provided they are stable as shown by computed tomography (CT) or magnetic
resonance imaging (MRI) scan for at least 4 weeks before Screening without evidence of cerebral edema. Patients on stable dose of corticosteroids or anticonvulsants arepermitted.8Any unresolved toxicity > Grade I (except alopecia) from previous anticancer therapy (including radiotherapy).9History of hemoptysis (> 1/2 teaspoon per event over the past 6 months) or evidence of inherited bleeding diathesis or coagulopathy with the risk of bleeding. Clinically
non-significant minor bleeding is acceptable.10A significant thrombotic or hemorrhagic event <6 months prior to Screening (includes hemoptysis [> 2.5 mL of red blood],gastrointestinal bleeding, hematemesis, CNShemorrhage, severe epistaxis or vaginal bleeding,cerebral infarction,transient
ischemic attacks, myocardial infarction, angina,uncontrolled coronary artery disease).11 Clinically serious non-healing wounds,or incompletely healed bone fracture at screening.12 Known hypersensitivity to any of the study drugs or their excipients, or history of clinically significant atopic allergy (eg,asthma including childhood asthma,urticarial).13Live/attenuated vaccine within 12 weeks prior to the Screening Visit.14History of myocardial infarction (<6 months prior to Screening), unstable angina, New
York Heart Association Grade II or greater, congestive heart failure, or serious cardiac
arrhythmia requiring medication.15History of poorly controlled hypertension or resting blood pressure >150/100 mmHgin the presence of a stable regimen of antihypertensive therapy.16Any major surgical procedure (risk of bleeding or wound healing complications) within 28 days prior to the screening.17History of active gastroduodenal ulcer, abdominal fistula as well as no gastrointestinalfistula,gastrointestinal perforation or intra-abdominal abscess within
6 months prior to Screening.18Clinically significant active infection requiring systemic therapy.19Known active Hepatitis B infection (according to local site standards) or active
Hepatitis C infection (Hepatitis C virus [HCV] antibody positive)the patient could be
included in the study if he/she is HCV RNA negative.20Known human immunodeficiency virus (HIV) infection (positive results from patient
history are accepted),syphilis,or active tuberculosis infection.21Patient considered unsuitable for inclusion by the Investigator (eg, inability tounderstand and/or comply with study requirements or presence of any condition,which, in the opinion of the Investigator,would not allow safe participation in the study).22Pregnant or lactating women.23Any planned dental surgical intervention during the study.24Patients who require permanent oral anticoagulation(eg warfarin,rivaroxaban,dabigatran,acenocumarol, etc.)treatment.
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Method of Generating Random Sequence
|
Computer generated randomization |
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Method of Concealment
|
Centralized |
|
Blinding/Masking
|
Double Blind Double Dummy |
Primary Outcome
Modification(s)
|
| Outcome |
TimePoints |
| To demonstrate clinical equivalence of the bevacizumab biosimilar (HD204) to reference bevacizumab (EU-Avastin®) given with chemotherapy by comparing the overall response rate (ORR) at Week 12 in Patients with Metastatic or RecurrentNon-squamous Non-small Cell Lung Cancer. |
Week 12 |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
To compare ORR at Week 6 and Week 18 between the bevacizumab biosimilar (HD204)
and reference bevacizumab (EU-Avastin®). Time point: at Week 6 and Week 18
• To compare ORR at Week 12 adjusted on dose intensity. Time point: at Week 12
• To compare the efficacy of bevacizumab biosimilar (HD204) to reference bevacizumab
(EU-Avastin®) in terms of duration of response (DoR), progression-free survival (PFS)
and overall survival (OS). Time point: throughout the study
|
To compare the safety and immunogenicity of bevacizumab biosimilar (HD204) and
reference bevacizumab (EU-Avastin®). Time point: throughout the study
• To compare bevacizumab Ctrough after administration of bevacizumab biosimilar
(HD204) and reference bevacizumab (EU-Avastin®). Time point: throughout the study
|
|
Target Sample Size
Modification(s)
|
Total Sample Size="592"
Sample Size from India="63"
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)
|
17/12/2019 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
27/11/2019 |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="1"
Months="0"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Open to Recruitment |
| Recruitment Status of Trial (India) |
Open to Recruitment |
|
Publication Details
|
NIL |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
|
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Brief Summary
|
This is a multicenter randomized,
double-blind, parallel group, equivalence, international phase
III trial to compare HD204 plus paclitaxel
and carboplatin (Arm A) versus EU-Avastin® plus
paclitaxel and carboplatin (Arm B). Patients
who have metastatic or recurrent non-squamous
non-small cell lung cancer (NSCLC) and have
their target lesion confirmed measurable by
independent
central imaging review (CIR) are eligible for the study.
|