Overview
Sponsor-declared trial summary
Phase
Therapeutic confirmatory (Phase III)
Status
Ended
Participants planned
755
Countries
7
Sites
23
Advanced or Metastatic Renal Cell Carcinoma
The purpose of this study is to determine whether Nivolumab Combined with Cabozantinib is safe and effective compared to Sunitinib in the treatment of Kidney cancer in patients with previously untreated, advanced, or cancer that has spread
Key facts
- Sponsor
- Bristol-Myers Squibb Services Unlimited Company
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Neoplasms [C04]
- Trial duration
- 27 Oct 2017 → 2 Apr 2026
- Decision date (initial)
- 2024-04-11
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- No
External identifiers
- EU CT number
- 2023-509711-83-00
- EudraCT number
- 2017-000759-20
- WHO UTN
- U1111-1193-0890
- ClinicalTrials.gov
- NCT03141177
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Safety, Therapy, Efficacy, Others, Pharmacokinetic
The purpose of this study is to determine whether Nivolumab Combined with Cabozantinib is safe and effective compared to Sunitinib in the treatment of Kidney cancer in patients with previously untreated, advanced, or cancer that has spread
Secondary objectives 3
- To compare overall survival (OS) of Arm A with Arm C in all randomized participants.
- To evaluate the objective response rate (ORR) per BICR in all randomized participants.
- To assess overall safety and tolerability in all treated participants.
Conditions and MedDRA coding
Advanced or Metastatic Renal Cell Carcinoma
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 21.1 | PT | 10050513 | Metastatic renal cell carcinoma | 100000004864 |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 3
- Histological confirmation of RCC with a clear-cell component, including participants who may also have sarcomatoid features
- Advanced (not amenable to curative surgery or radiation therapy) or metastatic (AJCC Stage IV) RCC
- No prior systemic therapy for RCC with the following exception: i) One prior adjuvant or neoadjuvant therapy for completely resectable RCC if such therapy did not include an agent that targets VEGF or VEGF receptors and if recurrence occurred at least 6 months after the last dose of adjuvant or neoadjuvant therapy
Exclusion criteria 3
- Any active CNS metastases
- Any active, known or suspected autoimmune disease
- Any condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Progression Free Survival (PFS) per blinded independent central review (BICR) of Arm A versus Arm C in all randomized participants
Secondary endpoints 4
- Overall Survival (OS) of Arm A versus Arm C
- Objective Response Rate (ORR)
- Incidence of adverse events (AEs)
- Incidence of Serious Adverse Events (SAEs)
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 4
OPDIVO 10 mg/mL concentrate for solution for infusion.
PRD2941375 · Product
- Active substance
- Nivolumab
- Substance synonyms
- BMS936558, ABP 206
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 240 mg/ml milligram(s)/millilitre
- Max total dose
- 12480 mg/ml milligram(s)/millilitre
- Max treatment duration
- 104 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01FF01 — -
- Marketing authorisation
- EU/1/15/1014/002
- MA holder
- BRISTOL-MYERS SQUIBB PHARMA EEIG
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
PRD191357 · Product
- Active substance
- Ipilimumab
- Other product name
- MDX-010
- Pharmaceutical form
- CONCENTRATE FOR SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 1 mg/kg milligram(s)/kilogram
- Max total dose
- 34 mg/kg milligram(s)/kilogram
- Max treatment duration
- 104 Week(s)
- Authorisation status
- Not Authorised
- MA holder
- BRISTOL-MYERS SQUIBB INTERNATIONAL CORPORATION
- Paediatric formulation
- No
- Orphan designation
- No
PRD191358 · Product
- Active substance
- Ipilimumab
- Other product name
- MDX-010
- Pharmaceutical form
- CONCENTRATE FOR SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 1 mg/kg milligram(s)/kilogram
- Max total dose
- 34 mg/kg milligram(s)/kilogram
- Max treatment duration
- 104 Week(s)
- Authorisation status
- Not Authorised
- MA holder
- BRISTOL-MYERS SQUIBB INTERNATIONAL CORPORATION
- Paediatric formulation
- No
- Orphan designation
- No
CABOMETYX 20 mg film-coated tablets
PRD4381882 · Product
- Active substance
- Cabozantinib
- Substance synonyms
- XL-184, Cyclopropane-1,1-dicarboxylic acid [4-(6,7-dimethoxy-quinolin-4-yloxy)-phenyl]-amide (4-fluoro-phenyl)-amide
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 40 mg milligram(s)
- Max total dose
- 73000 mg milligram(s)
- Max treatment duration
- 260 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01EX07 — -
- Marketing authorisation
- EU/1/16/1136/002
- MA holder
- IPSEN PHARMA
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Comparator 2
PRD505831 · Product
- Active substance
- Sunitinib
- Pharmaceutical form
- CAPSULE, HARD
- Route of administration
- ORAL USE
- Max daily dose
- 50 mg milligram(s)
- Max total dose
- 2166 mg milligram(s)
- Max treatment duration
- 260 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01EX01 — -
- Marketing authorisation
- EU/1/06/347/001
- MA holder
- PFIZER EUROPE MA EEIG
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- The product will be removed from the carton, over-labeled, and repackaged. There will be no changes to the composition or primary packaging of the marketed products.
PRD505881 · Product
- Active substance
- Sunitinib
- Pharmaceutical form
- CAPSULE, HARD
- Route of administration
- ORAL USE
- Max daily dose
- 50 mg milligram(s)
- Max total dose
- 2166 mg milligram(s)
- Max treatment duration
- 260 Week(s)
- Authorisation status
- Authorised
- ATC code
- L01EX01 — -
- Marketing authorisation
- EU/1/06/347/004
- MA holder
- PFIZER EUROPE MA EEIG
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- The product will be removed from the carton, over-labeled, and repackaged. There will be no changes to the composition or primary packaging of the marketed products.
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Bristol-Myers Squibb Services Unlimited Company
- Sponsor organisation
- Bristol-Myers Squibb Services Unlimited Company
- Address
- Plaza 254, Blanchardstown Corporate Park 2 Blanchardstown Corporate Park 2
- City
- Dublin 15
- Postcode
- D15 T867
- Country
- Ireland
Scientific contact point
- Organisation
- Bristol Myers Squibb International Corporation
- Contact name
- GSM-CT
Public contact point
- Organisation
- Bristol Myers Squibb International Corporation
- Contact name
- GSM-CT
Third parties 15
| Organisation | City, country | Duties |
|---|---|---|
| PPD Development LP ORG-100011560
|
Richmond, United States | Other |
| Accenture Solutions Private Limited ORG-100032592
|
Bangaluru, India | Data management, E-data capture |
| Accenture Solutions Private Limited ORG-100032592
|
Bangaluru, India | Other |
| Bioclinica Inc. ORG-100033079
|
Princeton, United States | Other |
| Worldwide Clinical Trials Early Phase Services LLC ORG-100032461
|
Austin, United States | Other |
| Q2 Solutions LLC ORG-100017000
|
Valencia, United States | Other |
| Myriad RBM Inc. ORG-100045698
|
Austin, United States | Other |
| Icon (Lr) Limited ORG-100042612
|
Dublin 18, Ireland | Other |
| Icon Laboratory Services Inc. ORG-100037135
|
Farmingdale, United States | Other |
| Accenture Solutions Private Limited ORG-100032592
|
Chennai, India | Other, Data management |
| Laboratory Corporation Of America Holdings ORG-100041800
|
Los Angeles, United States | Other |
| Parexel International (IRL) Limited ORG-100022780
|
Dublin 2, Ireland | Other, Interactive response technologies (IRT) |
| Icon Laboratory Services Inc. ORG-100037135
|
Farmingdale, United States | Other |
| Greenphire LLC ORG-100041621
|
King Of Prussia, United States | Other |
| Biostorage Technologies Inc. ORG-100013143
|
Indianapolis, United States | Other |
Locations
7 EU/EEA countries · 23 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Czechia | Ended | 12 | 2 |
| Germany | Ended | 32 | 3 |
| Greece | Ended | 36 | 2 |
| Italy | Ended | 70 | 7 |
| Poland | Ended | 55 | 3 |
| Romania | Ended | 25 | 1 |
| Spain | Ended | 35 | 5 |
| Rest of world
Israel, Brazil, Chile, Australia, Argentina, Russian Federation, United Kingdom, Turkey, Mexico
|
— | 490 | — |
Investigational sites
Fakultni Nemocnice Hradec Kralove
Klinika onkologie a radioterapie, Sokolska 581, 500 03, Novy Hradec Kralove
University Hospital Olomouc
Onkologicka klinika, Zdravotniku 248/7, 779 00, Olomouc
Universitaetsklinikum Tuebingen AöR
Klinik fuer Urologie, Studienambulanz, Hoppe-Seyler-Strasse 1, Nordstadt, Tuebingen
Klinikum rechts der Isar der TU Muenchen AöR
Urologische Klinik und Poliklinik, Ismaninger Strasse 22, Au-Haidhausen, Munich
Universitaetsklinikum Jena KöR
Klinik und Poliklinik fuer Urologie, Am Klinikum 1, Lobeda, Jena
Euromedica General Clinic Of Thessaloniki
Oncology Unit, Kallas Marias 11, Gravias 2, Thessaloniki
Alexandra Hospital
Department of Clinical Therapeutics, Hematology Oncology Department, Vassilissas Sofias Avenue 80, 115 28, Athens
Istituto Oncologico Veneto
Dipartimento di Oncologia Medica, Via Gattamelata 64, 35128, Padova
Ospedale San Raffaele S.r.l.
Oncologia Medica, Via Olgettina 60, 20132, Milan
Fondazione IRCCS Policlinico San Matteo
oncologia maedica, Viale Camillo Golgi 19, 27100, Pavia
Istituti Clinici Scientifici Maugeri In Forma Abbreviata Istituti Clinici Scientifici Maugeri O Anche Ics Maugeri O Maugeri S.p.A. Sb
UO di Oncologia Traslazionale, Via Salvatore Maugeri 10, 27100, Pavia
Azienda Ospedaliera Di Rilievo Nazionale Antonio Cardarelli
U.O. Oncologia Medica, Via Antonio Cardarelli 9, 80131, Naples
Azienda USL Toscana Sud Est
UOC Oncologia Medica, Ospedale Area Aretina Nord, Via Pietro Nenni 20/22, Arezzo
Azienda Ospedaliera S Maria Di Terni
S.C. Oncologia Medica, Viale Tristano Di Joannuccio 1, 05100, Terni
Wojewodzki Szpital Specjalistyczny W Bialej Podlaskiej
N/A, Ul. Terebelska 57/65, 21-500, Biala Podlaska
Centrum Onkologii Im. Prof. Franciszka Lukaszczyka W Bydgoszczy
N/A, Ul. Izabeli Romanowskiej 2, 85-796, Bydgoszcz
Copernicus Podmiot Leczniczy Sp. z o.o.
Wojewodzkie Centrum Onkologii, Al. Zwyciestwa 31/32, 80-219, Gdansk
Institute Of Oncology Prof. Dr. Ion Chiricuta Cluj-Napoca
Oncology, Strada Republicii 34-36, 400015, Cluj-Napoca
Vall D'hebron Institut De Recerca
Oncology, Passeig De La Vall D'hebron 119-129, 08035, Barcelona
University Hospital Virgen Del Rocio S.L.
Oncology, Avenida De Manuel Siurot S/n, 41013, Sevilla
Hospital Universitario 12 De Octubre
Oncology, Bloque D, Avenida De Cordoba Sn, Madrid
Hospital General Universitario Gregorio Maranon
Oncology, Calle Del Doctor Esquerdo 46, 28009, Madrid
Hospital Universitario Marques De Valdecilla
Oncology, Avenida Valdecilla Sn, 39008, Santander
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Czechia | 2017-11-30 | 2025-02-03 | 2018-01-03 | 2019-01-25 | |
| Germany | 2018-03-15 | 2024-08-19 | 2018-03-20 | 2019-02-11 | |
| Greece | 2018-03-14 | 2024-09-23 | 2018-04-16 | 2018-10-23 | |
| Italy | 2025-12-01 | 2025-12-30 | |||
| Poland | 2018-01-09 | 2026-04-01 | 2018-01-18 | ||
| Romania | 2018-11-13 | 2026-04-01 | 2018-11-23 | 2019-02-11 | |
| Spain | 2017-10-27 | 2025-03-05 | 2018-01-10 | 2018-12-27 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 49 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol_2023-509711-83-00 GR Redacted | 01 EU |
| Protocol (for publication) | D1_Protocol_2023-509711-83-00_Redacted | 02 EU |
| Protocol (for publication) | D1_Protocol_Admin_Letter_04_2023-509711-83-00_redacted | n/a |
| Protocol (for publication) | D1_Protocol_Admin_Letter_05_2023-509711-83-00_redacted | n/a |
| Protocol (for publication) | D1_Protocol_Admin_Letter_06_2023-509711-83-00-Redacted | 6 |
| Recruitment arrangements (for publication) | K1_Recruitment and Informed Consent Procedures Form_blank statement_ES | 1 |
| Recruitment arrangements (for publication) | K1_Recruitment and Informed Consent Procedures Form_blank statement_IT | 1 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements_blank document_GR | 1 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements_blank document_PL | 1 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements_blank document_RO | 1 |
| Subject information and informed consent form (for publication) | L1 SIS and ICF Addendum | 5.0 |
| Subject information and informed consent form (for publication) | L1 SIS and ICF for continouing tretment beyond disease progression | 2.0 |
| Subject information and informed consent form (for publication) | L1 SIS and ICF for Optional Genetic Research_Redacted | 3.0 |
| Subject information and informed consent form (for publication) | L1 SIS and ICF for Pregnant Partner_Redacted | 3.0 |
| Subject information and informed consent form (for publication) | L1 SIS and ICF Main_Redacted | 3.0 |
| Subject information and informed consent form (for publication) | L1_ SIS and ICF Addendum Arm A C with Track changes_PL | 8 |
| Subject information and informed consent form (for publication) | L1_ SIS and ICF Addendum Arm B with Track changes_PL | 9 |
| Subject information and informed consent form (for publication) | L1_ SIS and ICF Addendum_RO | 6 |
| Subject information and informed consent form (for publication) | L1_ SIS and ICF Data Protection_RO | 2.1 |
| Subject information and informed consent form (for publication) | L1_ SIS and ICF Greenphire_RO | NA |
| Subject information and informed consent form (for publication) | L1_ SIS and ICF Main_Redacted_RO | 5 |
| Subject information and informed consent form (for publication) | L1_ SIS and ICF Optional Biopsy_RO | 2 |
| Subject information and informed consent form (for publication) | L1_ SIS and ICF TBP_RO | 2 |
| Subject information and informed consent form (for publication) | L1_SIS and IC Addendum Arm A C_PL | 8 |
| Subject information and informed consent form (for publication) | L1_SIS and IC Addendum Arm B_PL | 9 |
| Subject information and informed consent form (for publication) | L1_SIS and IC Addendum Greenphire Direct Deposit_PL | 2 |
| Subject information and informed consent form (for publication) | L1_SIS and IC Addendum Optional Biopsy_PL | 2 |
| Subject information and informed consent form (for publication) | L1_SIS and IC Data Privacy_PL | N/A |
| Subject information and informed consent form (for publication) | L1_SIS and IC Main_PL_Redacted | 4 |
| Subject information and informed consent form (for publication) | L1_SIS and IC Treatment Beyond Progression _PL | 2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF addendum_unredacted_IT | 8 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Main_redacted_IT | 3 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Optional_redacted_IT | 3 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF PregnancyPartner_redacted_IT | 3 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF Progression_unredacted_IT | 2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Adenda 2_Redacted | 2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Adenda 6 to Main IC_arm A and C_Redacted | 6 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Main IC_arm A and C v5_Redacted | 5 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Main IC_arm B v5_Redacted | 5 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Optional tumor biopsy_Redacted | 2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_Treatment beyond progression_Redacted | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Sunitinib | n/a |
| Synopsis of the protocol (for publication) | D1 Protocol synopsis EU CT 2023-509711-83_PL | 1 |
| Synopsis of the protocol (for publication) | D1_EUCTR_Protocol Synopsis_IT_2023-509711-83-00 | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis 2023-509711-83_CZ_CS_public | 01 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis GR_2023-509711-83-00 | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol Synopsis RO_2023-509711-83 | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol Synopsis_EN 2023-509711-83-00 | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol Synopsis_ES 2023-509711-83-00 | 1 |
Application history
8 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-02-29 | Poland | Acceptable 2024-04-08
|
2024-04-10 |
| 2 | SUBSTANTIAL MODIFICATION | SM-2 | 2024-09-12 | Poland | Acceptable 2024-12-02
|
2024-12-04 |
| 3 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2025-02-06 | Acceptable 2024-12-02
|
2025-02-06 | |
| 4 | SUBSTANTIAL MODIFICATION | SM-3 | 2025-03-11 | Poland | Acceptable 2025-05-13
|
2025-05-14 |
| 5 | NON SUBSTANTIAL MODIFICATION | NSM-2 | 2025-07-16 | Acceptable 2025-05-13
|
2025-07-16 | |
| 6 | SUBSTANTIAL MODIFICATION | SM-5 | 2025-10-17 | Poland | Acceptable 2026-01-30
|
2026-01-30 |
| 7 | SUBSTANTIAL MODIFICATION | SM-6 | 2026-02-27 | Poland | Acceptable 2026-03-23
|
2026-03-27 |
| 8 | NON SUBSTANTIAL MODIFICATION | NSM-3 | 2026-05-14 | Poland | Acceptable 2026-03-23
|
2026-05-14 |