Trial of Sunitinib and/or Nivolumab Plus Chemotherapy in Advanced Soft Tissue and Bone Sarcomas

NCT03277924 | Completed Phase 1

• 1 other identifier: GEIS-52
• Study Type: interventional
• Target: 197
• Locations: 3 countries
• Sites: 13

Brief Summary

Phase I-II, single-arm, non-randomized, open-label, multicenter, international clinical trial, with two stages. Stage one has two cohorts (soft tissue sarcoma and bone sarcoma) and stage two has eight cohorts (DDCS, EMC, VS, SFT, CCS, ASPS, UPS, LMS and OS). Nine sites in Spain, 3 sites in Italy and 1 site in the United Kingdom. Stage 1 (PHASE 1 and PHASE 2) Objective: To determine the recommended dose of the sunitinib plus nivolumab combination for phase II part. To evaluate the efficacy of the sunitinib plus nivolumab combination as measured by the progression-free survival rate (PFSR) at 6 months in patients with advanced soft tissue and bone sarcomas. Treatment: Adult patients will receive an initial induction phase (IP) from day 1 to day 14 of sunitinib 37.5 mg/day followed by a maintenance phase (MP) of sunitinib 37.5 mg/day continuously + nivolumab 3 mg/kg intravenous every 2 weeks infused over 1 hour. If three or more DLTs occur from day 15 to 42, for an initial set of 10 patients, sunitinib dose will be lowered to 25 mg/day or treatment schedule will be changed to 2 weeks on and one week off until recovery from toxicities. Stage 2 C1 to 6 Objective: To evaluate the efficacy of the sunitinib plus nivolumab combination as measured by PFSR at 6 months (CS/DDCS, EMC, VS, SFT, CCS cohorts) and at 12 months (ASPS cohort). Treatment: Adult patients will receive an initial induction phase (IP) from day 1 to day 14 of sunitinib 37.5 mg/day followed by a maintenance phase (MP) of sunitinib 25mg/day continuously + nivolumab 240mg every 2 weeks. Pediatric patients will receive an initial IP from day 1 to day 14 of (\<18 years) sunitinib at 25 mg/day unless the body surface area (BSA) of the patient is \>1.7. If BSA is \>1.7, then sunitinib 37.5 mg/day will be given followed by a MP of sunitinib 25 mg/day continuously + nivolumab 240 mg every 2 weeks regimen (if weight ≥40 kg) or sunitinib 25 mg/day continuously + nivolumab 3 mg/kg every 2 weeks regimen (if weight \<40kg). C 7 Objective: To determine the MTD of the epirubicin + ifosfamide + nivolumab combination in undifferentiated pleomorphic sarcoma and of the doxorubicin + dacarbazine + nivolumab combination in leiomyosarcoma. Treatment:Cohort 7a dose level 0: Patients will receive epirubicin dose of 60 mg/m2/d, d1 and d2 IV 20 minutes; followed by ifosfamide 3 g/m2/d d1-3, IV 3h with MESNA protection (40% of total dose of ifosfamide in each administration at 0, 3 and 6 h from ifosfamide initiation). Once finished Ifosfamide infusion of day 3, nivolumab is administered during 30 minutes, at dose of 360 mg IV, Q3W. GCSF support is mandatory. If three or more DLTs occur nivolumab dose will be lowered to dose level -1. Cohort 7b dose level 0: Patients will receive doxorubicin at dose of 75 mg/m2/d, d1 IV 20 minutes; followed by dacarbazine 400 mg//m2/d IV 60 minutes. Dacarbazine is administered also on day 2 of cycle. Once finished Dacarbazine infusion of day 2, nivolumab is administered for 30 minutes, at dose of 360 mg IV, Q3W. GCSF support is mandatory. If three or more DLTs occur nivolumab dose will be lowered to dose level -1 where patients will receive doxorubicin at dose of 75 mg/m2/d, d1 IV 20 minutes; followed by dacarbazine 400 mg//m2/d IV 60 minutes. Dacarbazine is administered also on day 2 of cycle. Once finished dacarbazine infusion of day 2, nivolumab is administered for 30 minutes, at dose of 240 mg IV, Q3W. GCSF support is mandatory. One-year maintenance of nivolumab is foreseen in the absence of progressive disease. C 8 Objectives:To determine the MTD of the MAP + nivolumab combination (phase I). Proportion of patients achieving good pathological response (phase II) Treatment dose level 0: In the IP, patients will receive CDDP 120 mg/m2 in 48h IV infusion (days 1-2) followed by doxorubicin 75 mg/m2 in 48h IV infusion (days 3-4). CDDP and doxorubicin will be given on days 1-4 and 36-39. Nivolumab administration will start on day 4 at flat dose 240 mg (after the end of doxorubicin), being the following doses administered on days 18, 39, and 53 (240 mg). HD methotrexate at 12 g/m2 in 2-h infusion will be administered on days 22, 29, 57, and 64. Surgery will be performed after finishing IP. Adjuvant chemotherapy will be administered after surgery. During the MP patients will receive nivolumab on day 210, every two weeks up to day 364. If three or more DLTs occur, then nivolumab dose level -1 will be activated.

Conditions

Soft Tissue Sarcoma; Bone Sarcoma

Keywords

Dedifferentiated chondrosarcoma; Extraskeletal myxoid chondrosarcoma; Angiosarcoma; Hemangioendothelioma; Intimal sarcomas; Solitary fibrous tumor; Clear cell sarcoma; Alveolar soft-part sarcoma; Undifferentiated pleomorphic sarcoma; Leiomyosarcoma; Osteosarcoma; Synovial Sarcoma; Epithelioid Hemangioendothelioma; Epithelioid Sarcoma; Ewing's Sarcoma; Chondrosarcoma

Outcome Measures

Primary Outcomes (5)

• Stage 1 - PHASE 1

  The recommended dose of the sunitinib and nivolumab combination for phase II part will be determined by assessing adverse events according to CTCAE 4.0 and they will be used as a rule for escalating or diminishing dose levels according to the dose-limiting toxicities detailed in the protocol

  6 months

• Stage 1 - PHASE 2

  Progression-free survival rate (PFSR): Efficacy measured by the PFSR at 6 months according to RECIST 1.1. PFSR at 6 months is defined as the percentage of patients who did not experience progression or death due to any cause since enrollment until month 6 after enrollment.

  6 months

• Stage 2 - Cohort 1-6: Progression-free survival rate (PFSR)

  CS/DDCS, EMC, VS, SFT, and CCS cohorts: 6-month progression-free survival rate (PFSR): Efficacy measured by the PFSR at 6 months according to RECIST 1.1. PFSR at 6 months is defined as the percentage of patients who did not experience progression or death due to any cause since enrollmentuntil month 6 after enrollment. ASPS cohort: 12-month progression-free survival rate (PFSR): Efficacy measured by the PFSR at 12 months according to RECIST 1.1. PFSR at 12 months is defined as the percentage of patients who did not experience progression or death due to any cause since the date of enrollment until month 12 after enrollment.

  6 months for CS/DDCS, EMC, VS, SFT, and CCS and 12 months for ASPS

• Stage 2 - Cohort 7: Maximum tolerated dose (MTD)

  The maximum tolerated dose (MTD) of the epirubicin + ifosfamide + nivolumab combination will be determined by assessing adverse events according to CTCAE 5.0 and they will be used for adjusting dose levels according to the dose-limiting toxicities detailed in the protocol.

  1 year

• Stage 2 - Cohort 8: Maximum tolerated dose (MTD)

  The maximum tolerated dose (MTD) of the MAP + nivolumab combination will be determined by assessing adverse events according to CTCAE 5.0 and they will be used for adjusting dose levels according to the dose-limiting toxicities detailed in the protocol.

  1 year

Secondary Outcomes (11)

• Stage 1 and Stage 2 - Overall survival (OS)

  2 years

• Stage 1 and Stage 2 - Objective response rate (ORR)

  2 months

• Stage 2 - Cohort 1-6 Correlation between efficacy and potential predictive biomarkers

  2 years

• Stage 1 and Stage 2 - Safety profile: Adverse events

  3 years

• Stage 1 (PHASE 2) and Stage 2 - Cohort 1-6 Clinical outcome

  At 36 months

Study Arms (1)

Sunitinib and/or nivolumab plus chemotherapy in advanced STS and BS

EXPERIMENTAL

Stage 1: IP d1-14 sunitinib 37.5mg/d then MP sunitinib 37.5mg/d+nivolumab 3mg/kg ev 2w. Stage 2: C1-6: IP d1-14 sunitinib 37.5mg/d then MP sunitinib 25mg/d+nivolumab 240mg ev 2w. C7a level 0: Epirubicin 60mg/m2/d, d1,2, ifosfamide 3g/m2/d d1-3 and nivolumab 360mg. 3 or more DLTs level -1 same treatment than in level 0, but nivolumab 240mg. C7b level 0: Doxorubicin 75mg/m2/d, d1, dacarbazine 400mg/m2/d (also on d2) and nivolumab 360mg. 3 or more DLTs level -1 same tratment than in level 0, but nivolumab 240mg. GCSF support is mandatory. 1-year maintenance of nivolumab. C8 level 0: In the IP, CDDP 120mg/m2 (d1-2), doxorubicin 75mg/m2 in (d3-4 and d36-39), nivolumab 240mg (d5), and on d18,39,53 and methotrexate 12g/m2 on d22,29,57,64, surgery and MP with nivolumab on d210, every 2 weeks up to d364. 3 or more DLTs level -1, with nivolumab 360mg on d4,36, surgery and MP with nivolumab on d210, ev 3 weeks up to d364.

Drug: Sunitinib 37.5 MG, Sunitinib 25 MG [Sutent]; Drug: Nivolumab 100 MG/10 ML [Opdivo]; Drug: Epirubicin; Drug: Ifosfamide; Drug: Doxorubicin; Drug: Dacarbazine; Drug: Cisplatin; Drug: Methotrexate

Interventions

Sunitinib 37.5 MG, Sunitinib 25 MG [Sutent] DRUG

Treatment will continue until disease progression, development of unacceptable toxicity, non-compliance, withdrawal of consent by the patient or investigator decision.

Also known as: Sutent

Sunitinib and/or nivolumab plus chemotherapy in advanced STS and BS

Nivolumab 100 MG/10 ML [Opdivo] DRUG

Treatment will continue until disease progression, development of unacceptable toxicity, non-compliance, withdrawal of consent by the patient or investigator decision.

Also known as: Opdivo

Sunitinib and/or nivolumab plus chemotherapy in advanced STS and BS

Epirubicin DRUG

Treatment will continue until disease progression, development of unacceptable toxicity, non-compliance, withdrawal of consent by the patient or investigator decision.

Sunitinib and/or nivolumab plus chemotherapy in advanced STS and BS

Ifosfamide DRUG

Treatment will continue until disease progression, development of unacceptable toxicity, non-compliance, withdrawal of consent by the patient or investigator decision.

Sunitinib and/or nivolumab plus chemotherapy in advanced STS and BS

Doxorubicin DRUG

Treatment will continue until disease progression, development of unacceptable toxicity, non-compliance, withdrawal of consent by the patient or investigator decision.

Sunitinib and/or nivolumab plus chemotherapy in advanced STS and BS

Dacarbazine DRUG

Treatment will continue until disease progression, development of unacceptable toxicity, non-compliance, withdrawal of consent by the patient or investigator decision.

Sunitinib and/or nivolumab plus chemotherapy in advanced STS and BS

Cisplatin DRUG

Treatment will continue until disease progression, development of unacceptable toxicity, non-compliance, withdrawal of consent by the patient or investigator decision.

Sunitinib and/or nivolumab plus chemotherapy in advanced STS and BS

Methotrexate DRUG

Treatment will continue until disease progression, development of unacceptable toxicity, non-compliance, withdrawal of consent by the patient or investigator decision.

Sunitinib and/or nivolumab plus chemotherapy in advanced STS and BS

Eligibility Criteria

• Age: 12 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Stage 1
• Patients must provide written informed consent prior to performance of study-specific procedures and must be willing to comply with treatment and follow-up. Informed consent must be obtained prior to start of the screening process. Procedures conducted as part of the patient's routine clinical management (e.g. blood count, imaging tests, etc.) and obtained prior to signature of informed consent may be used for screening or baseline purposes as long as these procedures are conducted as specified in the protocol.
• Age: 18-80 years.
• Histologic diagnosis of soft tissue sarcoma (undifferentiated pleomorphic sarcoma, synovial sarcoma, alveolar soft part sarcoma, clear cell sarcoma, angiosarcoma, epithelioid hemangioendothelioma, solitary fibrous tumor,epithelioid sarcoma and extraskeletal myxoid chondrosarcoma) or bone sarcoma (osteosarcoma/high grade bone sarcoma, Ewing's sarcoma, chondrosarcoma and dedifferentiated chondrosarcoma) confirmed by central pathology review. Mandatory paraffin embedded tumor blocks must be provided for all subjects without exception for biomarker analysis before treatment (first biopsy) and at end of month 3 or earlier (second biopsy).
• Metastatic/advanced disease in progression in the last 6 months.
• Measurable disease according to RECIST 1.1 criteria.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.
• Adequate hepatic, renal, cardiac, and hematologic function.
• Laboratory tests as follows:
• Absolute neutrophil count ≥ 1,200/mm³
• Platelet count ≥ 100,000/mm³
• Bilirubin ≤ 1.5 mg/dL
• PT and INR ≤ 1.5
• AST and ALT ≤ 2.5 times upper limit of normal
• Creatinine ≤ 1.5 mg/dL

You may not qualify if:

• Stage 1
• Four or more previous lines of chemotherapy for the advanced disease.
• Previous anti-programmed death-1 (PD-1), anti-programmed death-ligand 1 (PD-L1), anti PD-L2 or anti CTLA-4 antibody.
• Prior immune-related adverse event (Grade 3 or higher immune-related pneumonitis, hepatitis, colitis, endocrinopathy) with prior immunotherapy (e.g. cancer vaccine, cytokine, etc.).
• Active, known or suspected autoimmune disease.
• A condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
• Uncontrolled intercurrent illness including (not limited to): symptomatic congestive heart failure (CHF) (New York Heart Association \[NYHA\] III/IV), unstable angina pectoris or coronary angioplasty, or stenting within 24 weeks prior to registration, unstable cardiac arrhythmia (ongoing cardiac dysrhythmias of NCI CTCAE version 4.0 Grade \>= 2), known psychiatric illness that would limit study compliance, intra-cardiac defibrillators, known cardiac metastases, or abnormal cardiac valve morphology (\>= Grade 3).
• Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection.
• Other disease or illness within the past 6 months, including any of the following: • Myocardial infarction Severe or unstable angina • Coronary or peripheral artery bypass graft • Symptomatic congestive heart failure • Cerebrovascular accident or transient ischemic attack • Pulmonary embolism 9. Evidence of a bleeding diathesis. 10. Ongoing cardiac dysrhythmias \> Grade 2. 11. Uncontrolled hypertension, defined as blood pressure \> 150/100 mm Hg despite optimal medical therapy. 12. Psychiatric illness or social situation that would preclude study compliance. 13. Pre-existing thyroid abnormality, defined as abnormal thyroid function tests despite medication. 14. Prolonged QTc interval (i.e., QTc \> 450 msec for males or QTc \> 470 msec for females) on baseline ECG. 15. Hemorrhage ≥ Grade 3 in the past 4 weeks. 16. History of allergy to study drug components. 17. Previous anticoagulants due to thrombotic events. 18. History of another cancer with the exception of adequately treated basal cell carcinoma or cervical cancer in situ. 19. Presence of brain or central nervous system metastases.
• Stage 2
• Cohort 1-6
• Four or more previous lines of chemotherapy.
• Previous anti-programmed death-1 (PD-1), anti-programmed death-ligand 1 (PD-L1), anti PD-L2 or anti CTLA-4 antibody.
• Prior immune-related adverse event (Grade 3 or higher immune-related pneumonitis, hepatitis, colitis, endocrinopathy) with prior immunotherapy (e.g. cancer vaccine, cytokine, etc.).
• Active, known or suspected autoimmune disease.

Sponsors & Collaborators

• Grupo Espanol de Investigacion en Sarcomas: lead

Study Sites (13)

Istituto Ortopedico Rizzoli

Bologna, 40136, Italy

Location

Candiolo Cancer Institute - FPO, IRCCS

Candiolo, 10060, Italy

Location

Istituto Nazionale dei Tumori

Milan, 20133, Italy

Location

Hospital Universitario Fundación Jiménez Díaz

Madrid, Madrid, 28040, Spain

Location

Complejo Hospitalario Universitario de Canarias

San Cristóbal de La Laguna, Santa Cruz De Tenerife, 38320, Spain

Location

Hospital Universitari Vall d'Hebrón

Barcelona, 08035, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, 08041, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Universitario Virgen del Rocío

Seville, 41013, Spain

Location

Hospital Universitari i Politècnic La Fe

Valencia, 46026, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, 50009, Spain

Location

University College London Hospitals NHS Foundation Trust

London, NW1 2PG, United Kingdom

Location

Related Publications (3)

• Martin-Broto J, Diaz-Beveridge R, Moura D, Ramos R, Martinez-Trufero J, Carrasco I, Sebio A, Gonzalez-Billalabeitia E, Gutierrez A, Fernandez-Jara J, Hernandez-Vargas L, Cruz J, Valverde C, Hindi N. Phase Ib Study for the Combination of Doxorubicin, Dacarbazine, and Nivolumab as the Upfront Treatment in Patients With Advanced Leiomyosarcoma: A Study by the Spanish Sarcoma Group (GEIS). J Clin Oncol. 2025 Jan 20;43(3):297-307. doi: 10.1200/JCO.24.00358. Epub 2024 Oct 2.

  PMID: 39356980 DERIVED

• Martin-Broto J, Hindi N, Grignani G, Martinez-Trufero J, Redondo A, Valverde C, Stacchiotti S, Lopez-Pousa A, D'Ambrosio L, Gutierrez A, Perez-Vega H, Encinas-Tobajas V, de Alava E, Collini P, Pena-Chilet M, Dopazo J, Carrasco-Garcia I, Lopez-Alvarez M, Moura DS, Lopez-Martin JA. Nivolumab and sunitinib combination in advanced soft tissue sarcomas: a multicenter, single-arm, phase Ib/II trial. J Immunother Cancer. 2020 Nov;8(2):e001561. doi: 10.1136/jitc-2020-001561.

  PMID: 33203665 DERIVED

• Hattinger CM, Patrizio MP, Magagnoli F, Luppi S, Serra M. An update on emerging drugs in osteosarcoma: towards tailored therapies? Expert Opin Emerg Drugs. 2019 Sep;24(3):153-171. doi: 10.1080/14728214.2019.1654455. Epub 2019 Aug 14.

  PMID: 31401903 DERIVED

MeSH Terms

Conditions

Sarcoma; Bone Neoplasms; Chondrosarcoma, Extraskeletal Myxoid; Hemangiosarcoma; Hemangioendothelioma; Solitary Fibrous Tumors; Sarcoma, Clear Cell; Sarcoma, Alveolar Soft Part; Histiocytoma, Malignant Fibrous; Leiomyosarcoma; Osteosarcoma; Sarcoma, Synovial; Hemangioendothelioma, Epithelioid; Sarcoma, Ewing; Chondrosarcoma

Interventions

Sunitinib; Nivolumab; Epirubicin; Ifosfamide; Doxorubicin; Dacarbazine; Cisplatin; Methotrexate

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Bone Diseases; Musculoskeletal Diseases; Neoplasms, Vascular Tissue; Hemangioma; Neoplasms, Fibrous Tissue; Neoplasms, Connective Tissue; Neoplasms, Muscle Tissue; Histiocytoma; Neoplasms, Bone Tissue

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Cyclophosphamide; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Oxazines; Triazenes; Imidazoles; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Aminopterin; Pterins; Pteridines

Study Officials

• Javier Martín Broto

  Hospital Universitario Fundación Jiménez Díaz

  STUDY DIRECTOR

• Andrés Redondo

  Hospital Universitario La Paz

  PRINCIPAL INVESTIGATOR

• Claudia Valverde

  Hospital Universitari Vall d'Hebrón

  PRINCIPAL INVESTIGATOR

• Antonio López Pousa

  Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau

  PRINCIPAL INVESTIGATOR

• Roberto Diaz de Beveridge

  Hospital Universitario La Fe

  PRINCIPAL INVESTIGATOR

• Javier Martínez Trufero

  Hospital Miguel Servet

  PRINCIPAL INVESTIGATOR

• Irene Carrasco

  Hospitales Universitarios Virgen del Rocío

  PRINCIPAL INVESTIGATOR

• Enrique González

  Hospital Universitario 12 de Octubre

  PRINCIPAL INVESTIGATOR

• Josefina Cruz

  Hospital Universitario de Canarias

  PRINCIPAL INVESTIGATOR

• Silvia Stacchiotti

  Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

  PRINCIPAL INVESTIGATOR

• Giovanni Grignani

  Candiolo Cancer Institute - FPO, IRCCS

  PRINCIPAL INVESTIGATOR

• Emanuela Palmerini

  Istituto Ortopedico Rizzoli

  PRINCIPAL INVESTIGATOR

• Sandra Strauss

  University College London Hospitals

  PRINCIPAL INVESTIGATOR

• Cristina Mata

  Hospital General Universitario Gregorio Marañón

  PRINCIPAL INVESTIGATOR

• Antonio Casado

  Hospital Clínico Universitario San Carlos

  PRINCIPAL INVESTIGATOR

• Alejandro Pérez Fidalgo

  Hospital Clínico Universitario de Valencia

  PRINCIPAL INVESTIGATOR

• Luis De Sande

  Hospital Universitario de León

  PRINCIPAL INVESTIGATOR

• Alba Rubio

  Hospital Infantil Universitario Niño Jesús

  PRINCIPAL INVESTIGATOR

• Jerónimo Martínez

  Hospital Universitario Virgen de la Arrixaca

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Phase I-II, single-arm, non-randomized, open-label, multicenter, international clinical trial

Study Record Dates

• First Submitted: August 3, 2017
• First Posted: September 11, 2017
• Study Start: May 31, 2017
• Primary Completion: June 30, 2024
• Study Completion: June 30, 2024
• Last Updated: August 13, 2024

Record last verified: 2024-08

Locations

GB (1); IT (3); ES (9)