| CTRI Number |
CTRI/2020/10/028626 [Registered on: 26/10/2020] Trial Registered Prospectively |
| Last Modified On: |
27/03/2023 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug
Biological |
| Study Design |
Single Arm Study |
|
Public Title of Study
|
A Phase 4 Study of Combination Nivolumab and Ipilimumab in Patients with Advanced Renal Cell Carcinoma in India |
|
Scientific Title of Study
|
A Phase 4 Study of Nivolumab in Combination with Ipilimumab in Patients with Previously Untreated Advanced Renal Cell Carcinoma and Intermediate- or Poor-risk Factors Conducted in India |
| Trial Acronym |
There is no Trial Acronym. The study number is CA209-7C9 |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| CA209-7C9 v 1.0_06 Feb 2020 |
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
Modification(s)
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| Name |
Dr Kartik Doshi |
| Designation |
Study director |
| Affiliation |
Bristol Myers Squibb India Pvt. Ltd. |
| Address |
The India Bulls Finance Centre, 6th Floor, Tower 1, Senapati Bapat
Marg, Elphinstone (W), Mumbai - India Bristol Myers Squibb India
Pvt. Ltd.
Mumbai (Suburban)
MAHARASHTRA
400013
India |
| Phone |
91-2266288600 |
| Fax |
|
| Email |
Kartik.Doshi@bms.com |
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Details of Contact Person
Public Query
|
| Name |
Shilpi Sinha |
| Designation |
Senior Site Manager |
| Affiliation |
Bristol Myers Squibb India Pvt. Ltd |
| Address |
The India Bulls Finance Centre, 6th Floor, Tower 1, Senapati Bapat
Marg, Elphinstone (W), Mumbai - India Bristol Myers Squibb India
Pvt. Ltd
Mumbai (Suburban)
MAHARASHTRA
400013
India |
| Phone |
91-2266288645 |
| Fax |
|
| Email |
Shilpi.Sinha@bms.com |
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Source of Monetary or Material Support
|
| Bristol Myers Squibb Research and Development |
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Primary Sponsor
|
| Name |
BRISTOL MYERS SQUIBB INDIA PRIVATE LIMITED |
| Address |
BRISTOL MYERS SQUIBB INDIA PRIVATE LIMITED The India Bulls Finance Centre, 6th Floor,
Tower 1, Senapati Bapat Marg, Elphinstone (W), Mumbai - 400013 |
| Type of Sponsor |
Pharmaceutical industry-Global |
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Details of Secondary Sponsor
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Countries of Recruitment
|
India |
Sites of Study
Modification(s)
|
| No of Sites = 12 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Ranjit Sahoo |
All India Institute of Medical Sciences |
Dr. B.R.A. Institute Rotary Cancer Hospital, All India Institutes of Medical Sciences, Room no 218, Department of Medical Oncology, Ansari Nagar, Department of Medical Oncology, New Delhi - 110029
New Delhi
DELHI |
9013956187
drranjitmd@gmail.com |
| Dr Senthil Rajappa |
Basavatarakam Indo American Cancer Hospital & Research Institute |
Basavatarakam Indo American Cancer Hospital & Research Institute, Road no. 10, Banjara Hills, Hyderabad - 500034, Telanagana, India
Hyderabad
TELANGANA |
9849213102
senthiljrajappa@gmail.com |
| Dr Shekar Patil |
HealthCare Global Enterprises Limited |
HealthCare Global Enterprises Limited, HCG Towers, No. 08, P. kalingarao Road, Sampangiram nagar, Bangalore – 560027
Bangalore
KARNATAKA |
8033466170
spassociates6@gmail.com |
| Dr Chirag Desai |
Hemato Oncology Clinic Ahmedabad Pvt Ltd |
Hemato Oncology Clinic Ahmedabad Pvt Ltd, Opp. HDFC Bank, Beside Occura Eye Hospital & Pandit Deeyandayal Autitorium, Rajpath Club Road Lane, Off S. G. Highway, Ahmedabad - 380054, Gujarat, India
Ahmadabad
GUJARAT |
9824047561
chiragdesai.oncology@gmail.com |
| Dr Sandeep Goyle |
Kokilaben Dhirubhai Ambani Hospital |
Kokilaben Dhirubhai Ambani Hospital and Medical Research Institute, Rao Saheb, Achutrao Patwardhan Marg, Four Bungalows, Andheri West, Mumbai - 400053
Mumbai
MAHARASHTRA |
9322527910
sandeep.goyle@kokilabenhospitals.com |
| Dr Amit Rauthan |
Manipal Hospital |
Manipal Hospital, # 98, HAL Airport Road, Bangalore - 560017
Bangalore
KARNATAKA |
9880463958
amitrauthan@yahoo.com |
| Dr Vashishth Maniar |
Mumbai Oncocare Centre |
Mumbai Oncocare Centre (Unit of Cellcure Cancer Centre Pvt Ltd), 2nd floor, Majithia apartment, God’s Gift Premises Co-op Society Ltd, S.V. Road, Vile Parle - 400056
Mumbai
MAHARASHTRA |
98198334571
vpm@mocindia.co.in |
| Dr Chandrakanth M V |
Narayana Superspeciality Hospital |
Narayan Superspeciality Hospital,
120/1, Andul Road, Haora - 71103, West Bengal
Haora
WEST BENGAL |
7738519198
drmvch@gmail.com |
| Dr Vineet Talwar |
Rajiv Gandhi Cancer Institute & Research Centre |
Rajiv Gandhi Cancer Institute & Research Centre, Department of Medical Oncology Sir Chotu Ram Marg, Rohini Institutional Area, Sector 5, Rohini, Delhi - 110085
New Delhi
DELHI |
9810241512
drvineettalwar@yahoo.com |
| Dr Lakshmi Haridas K |
Regional Cancer Centre |
Regional Cancer Centre, Department of Medical Oncology, Medical College P.O, Thiruvanthapuram - 695011
Thiruvananthapuram
KERALA |
9447206106
lakshmiharidasrcc@gmail.com |
| Dr Minish Jain |
Ruby Hall Clinic |
Grant Medical Foundation Ruby Hall clinic, 40 Sassoon Road, Pune - 411001
Pune
MAHARASHTRA |
9823133390
minishjain009@gmail.com |
| Dr Amit Joshi |
Tata Memorial Hospital |
Tata Memorial Hospital, Dept of medical oncology, HBB, 11th floor, room no:1105, Dr. E Borges Road,
Parel, Mumbai-400012
Mumbai
MAHARASHTRA |
9769331525
dramitjoshi74@gmail.com |
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Details of Ethics Committee
Modification(s)
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| No of Ethics Committees= 11 |
| Name of Committee |
Approval Status |
| Ethics Committee All India Institute of Medical Sciences |
Approved |
| Ethics Committee of CIMS |
Approved |
| Ethics Committee of Manipal Hospitals |
Approved |
| HCG Central Ethics Committee |
Approved |
| Human Ethics Committee RCC |
Approved |
| INSTITUTIONAL ETHICS COMMITTEE Kokilaben Dhirubhai Ambani Hospital & Medical Research Institute |
Approved |
| Institutional Review Board Institutional Review Board Institutional Review Board Rajiv Gandhi Cancer Institute & Research Centre |
Approved |
| Mumbai Oncocare Central IEC |
Approved |
| NSH ETHICS COMMITTEE |
Approved |
| Poona Medical Research Foundation |
Approved |
| TMH, Institutional Ethics Committee-II |
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 |
(1) ICD-10 Condition: C790||Secondary malignant neoplasm of kidney and renal pelvis, |
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Intervention / Comparator Agent
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| Type |
Name |
Details |
| Intervention |
Nivolumab in Combination with Ipilimumab |
Participants will receive a combination dosing regimen of nivolumab 3 mg/kg as a 30-minute IV
infusion + ipilimumab 1 mg/kg as a 30-minute IV infusion Q3W followed by a single-dose agent
of nivolumab 3 mg/kg Q2W for a maximum of 52 weeks or until treatment is no longer tolerated
by the participant or withdrawal of consent. The first dose is to be administered within 28 days
after signing the ICF. |
| Comparator Agent |
Not APPLICABLE |
Not APPLICABLE |
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Inclusion Criteria
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| Age From |
18.00 Year(s) |
| Age To |
99.00 Year(s) |
| Gender |
Both |
| Details |
1) Signed Written Informed Consent
a) Participants must have signed and dated an Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved written ICF in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocolrelated procedures that are not part of normal participant care.
b) Participants must be willing and able to comply with scheduled visits, treatment schedule,laboratory tests, biomarker and PK testing, and other requirements of the study.
2) Type of Participant and Target Disease Characteristics
a) Histological confirmation of renal carcinoma with clear cell component including participants who may have sarcomatoid features. Advanced (not amenable to curative surgery or radiation therapy) RCC or mRCC.
b) No prior systemic therapy for RCC with the following exception:
i) One prior adjuvant or neoadjuvant therapy for completely resected RCC
2b). These drugs must be discontinued 6 months prior to study entry. All AEs related to prior adjuvant or neoadjuvant therapy must have returned to baseline, and eligible patients must not have experienced severe or life-threatening immune-related AEs except those that are unlikely to reoccur with standard countermeasures (eg, hormone replacement after adrenal crisis).
c) Measurable disease lesion by CT or MRI per RECIST 1.1 criteria. Radiated lesions cannot be used as measurable lesions unless there is clear evidence of progression.
d) KPS of at least 70%
e) Qualifies as intermediate or poor risk by meeting least 1 of the following prognostic factors as per the IMDC criteria:
i) KPS less than 80
ii) Less than 1 year from diagnosis including original localized disease (if applicable) to study enrollment
iii) Hemoglobin less than the lower limit of normal
iv) Corrected calcium concentration greater than 10 mg/dL.
v) Absolute neutrophil count greater than the ULN
vi) Platelet count greater than the ULN
3) Age and Reproductive Status
a) Male and female participants must be 18 years or older at the time of informed consent(ICF)
b) Women of childbearing potential (WOCBP) must have a negative serum or urine
pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human horionic gonadotropin [HCG]) within 24 hours prior to the start of study treatment.
c) Women must not be breastfeeding.
d) WOCBP must agree to follow instructions for method(s) of contraception for the duration of study treatment plus 5 half-lives of study treatment plus 30 days (duration of ovulatory cycle) for a total of 5 months after the last dose of study treatment.
e) Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception and fetal protection (Appendix 4) for the duration of treatment with nivolumab and ipilimumab plus 7 months after the last dose of study treatment. In addition, male participants must be willing to refrain from sperm donation during this time.
f) WOCBP who are continuously not heterosexually active are also exempt from
contraceptive requirements, and still must undergo pregnancy testing as described in this section.
g) Azoospermic males are exempt from contraceptive requirements unless the potential exists for fetal toxicity due to study drug being present in seminal fluid, even if the participant has undergone a successful vasectomy or if the partner is pregnant.
4) Other Inclusion Criteria
a) Indian participants with Indian ethnicity living in India.
b) An FFPE tissue block (prefer) or a minimum of 20 unstained slides [15 minimum if tissue is limited] of tumor tissue obtained from core biopsy, punch biopsy, excisional biopsy,surgical specimen or, archival tissue (if above is not available), preferably within 3 months,but no more than 12 months prior to enrollment, with an associated pathology report and with no intervening systemic anti-cancer treatment between time of acquisition and treatment assignment, must be sent to central laboratory during screening and must be
received by the central vendor (block or unstained slides) in order to start a participant on study treatment. Fine needle aspiration and biopsies of bone lesions that do not have a soft tissue component are unacceptable for submission.
c) The tissue submitted will be assessed for quality, and only those participants who meet tissue quality thresholds can have their treatment assigned. Central laboratory must provide IRT with confirmation of receipt of evaluable tumor tissue prior to participant treatment assignment. Subjects should not have received any systemic anti-cancer therapy after the
date that the submitted tumor tissue was obtained.
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| ExclusionCriteria |
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Method of Generating Random Sequence
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Not Applicable |
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Method of Concealment
|
Not Applicable |
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Blinding/Masking
|
Not Applicable |
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Primary Outcome
|
| Outcome |
TimePoints |
To assess the incidence of high-grade (CTCAE v5
Grade 3 to 4 and Grade 5) IMAEs in intermediateor
poor-risk participants with previously untreated,
advanced RCC who are treated with combination
therapy of nivolumab 3 mg/kg administered
intravenously over a period of 30 minutes Q3W for
the first 4 doses in combination with intravenous
ipilimumab 1 mg/kg over a period of 30 minutes,
followed by nivolumab 3 mg/kg Q2W administered
IV over a period of 30 minutes |
To assess the incidence of high-grade (CTCAE v5
Grade 3 to 4 and Grade 5) IMAEs in intermediateor
poor-risk participants with previously untreated,
advanced RCC who are treated with combination
therapy of nivolumab 3 mg/kg administered
intravenously over a period of 30 minutes Q3W for
the first 4 doses in combination with intravenous
ipilimumab 1 mg/kg over a period of 30 minutes,
followed by nivolumab 3 mg/kg Q2W administered
IV over a period of 30 minutes |
|
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Secondary Outcome
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| Outcome |
TimePoints |
To characterize the outcome of all high grade
(CTCAE v5 Grade 3 to 4 and Grade 5) IMAEs in
intermediate or poor risk participants with
previously untreated, advanced RCC. |
EVERY 8 WEEKS |
To assess the effectiveness of nivolumab in
combination with ipilimumab by measuring ORR,
TTR, and DOR, using RECIST 1.1. |
Every 8 weeks |
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Target Sample Size
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Total Sample Size="100"
Sample Size from India="100"
Final Enrollment numbers achieved (Total)= "0"
Final Enrollment numbers achieved (India)="101" |
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Phase of Trial
|
Phase 4 |
|
Date of First Enrollment (India)
|
30/10/2020 |
| Date of Study Completion (India) |
17/01/2023 |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Date Missing |
|
Estimated Duration of Trial
|
Years="2"
Months="0"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Not Applicable |
| Recruitment Status of Trial (India) |
Completed |
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Publication Details
|
NIL |
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Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
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Brief Summary
|
A Phase 4 Study of Nivolumab in Combination with Ipilimumab in Patients with Previously Untreated Advanced Renal Cell Carcinoma and Intermediate- or Poor-risk Factors Conducted in India -[CA209-7C9]
This study is done a part of the regulatory commitment for marketing approval for Ipi and Nivo in IL RCC |