Head and Neck CancerNCT03539198
Study of Proton SBRT and Immunotherapy for Recurrent/Progressive Locoregional or Metastatic Head and Neck Cancer
An observational study of Head and Neck Cancer, run by Mayo Clinic at 2 sites in United States.
Trial summary
This study observes the clinical efficacy of combining proton SBRT with PD-1 blockade immunotherapy in both the locoregionally recurrent and metastatic settings. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Head and Neck Cancer
- What is being tested?
- Proton Stereotactic Body Radiation Therapy (SBRT) (5 fractions; 3500-4500 cGy), Proton Stereotactic Body Radiation Therapy (SBRT) (3-5 fractions; various dose and fractionation regimens depending on treatment site). and Nivolumab 3 mg/kg IV q2 weeks
- Type of treatment
- Injection or infusion, Surgery or procedure
- How many people
- 19 participants
- Where
- 2 sitesUnited States
- Study dates
- 3 Jul 2018to 6 Jan 2020
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: patients with locoregional or metastatic head and neck cancers
Who may be able to join
- Age ≥18 years old whose multidisciplinary care team has determined that the treatments outlined in the protocol are the treating physicians' equipoised clinical recommendation, the multidisciplinary head \& neck tumor board's recommendation, and that any reasonable alternative treatments have been reviewed with the subject.
- Signed written informed consent in accordance with regulatory and institutional guidelines.
- Must be willing to comply with scheduled visits, treatment schedule, laboratory testing and other study obligations. Patients must be receiving SOC treatment for recurrent or progressive Head and Neck cancer. Please refer to UCM procedural manual.
- Histologically confirmed head and neck squamous cell carcinoma from any of the primary sites: oral cavity, pharynx, larynx, nasopharynx, sinonasal, cutaneous, or unknown head and neck primary.
- Subjects with head and neck squamous cell carcinoma that has progressed during chemotherapy with a platinum-based drug or that has recurred or metastasized after platinum-based chemotherapy or in patients with an intolerance to or contraindication for platinum-based chemotherapy will be eligible.
- ECOG performance status 0-2
Show all 24Show fewer
- Subjects enrolled on the METASTATIC ARM must have at least two (≥) lesions:
- One lesion must be safely amenable to irradiation with stereotactic body radiation therapy per the treating radiation oncologist. Prior radiation to this lesion is allowed if given ≥ 6 months prior. One lesion must be measurable by CT or MRI per iRECIST 1.1 criteria and should be separate from the lesion to be irradiated. If this target lesion has been previously irradiated, there must be documented disease progression after radiation per RECIST 1.1.
- Any prior radiotherapy must have been completed at least 3 weeks prior to enrollment.
- Adequate bone marrow, hepatic, and renal function based on screening lab values within 35 days prior to beginning immunotherapy:
- WBC ≥ 2 K/microliter
- Neutrophils ≥ 1.5 K/microliter
- Platelets ≥ 100 K/microliter
- Hemoglobin ≥ 9.0 g/deciliter
- Serum Creatinine ≤ 1.5 x ULN or creatinine clearance > 40ml/min using the Cockcroft-Gault formula.
- Female CrCl = (140 - age in years) x weight in kg x 0.85 72 x serum creatinine in mg/dL
- Male CrCl = (140 - age in years) x weight in kg x 1.00 72 x serum creatinine in mg/dL
- AST/ALT ≤ 3 x ULN
- Total bilirubin <1.5 x ULN (except subjects with Gilbert Syndrome who can have total bilirubin <3.0 mg/deciliter).
- Women of childbearing potential must have a negative serum or urine pregnancy test within 10 days prior to beginning immunotherapy.
- Women of childbearing potential (WOCBP) must agree to follow instructions for method(s) of contraception from time of enrollment for the duration of treatment with nivolumab and for 6 months after discontinuation of nivolumab. Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year. Men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 6 months after the last dose of nivolumab.
- Ability to complete questionnaire(s) by themselves or with assistance.
- Insurance approval or personal pay for SBRT.
- Patient may undergo palliative surgery prior to postoperative proton SBRT and remain in the metastatic arm of the study, as long as the patient meets the other aforementioned criteria relating to the metastatic arm. Surgery is allowable for the locoregionally recurrent arm as per the study schema.
Who cannot join
- Active brain metastases or leptomeningeal disease. Note: Treated brain metastases (e.g. GammaKnife or surgical resection) are eligible if these have been treated and are without MRI evidence of progression for at least 8 weeks after treatment. MRI must be performed within 35 days prior tobeginning immunotherapy.
- Histologically confirmed non-squamous histologies including salivary gland or other non-squamous histologies (e.g. mucosal melanoma) are not allowed; exception WHO Type I-III nasopharynx, which are allowed.
- Subjects with active autoimmune disease or on steroid therapy of >10 mg/day prednisone or equivalent.
- Subjects who have undergone bone marrow or solid organ transplantation.
- Known HIV, hepatitis B or C infection.
- Treatment with chemotherapy, radiation therapy or immunotherapy including investigational agents within 25 days of beginning immunotherapy.
Show all 9Show fewer
- Women that are breastfeeding or pregnant.
- Any concurrent chemotherapy, hormonal therapy, immunotherapy, or investigational therapy apart from the prescribed treatment per protocol.
- Other active non-head and neck malignancy <1 year prior to registration. If there is a history of prior distinct malignancy, they must not be receiving chemotherapy, radiotherapy, or immunotherapy for their other disease at the time of protocol enrollment. Exceptions include: Non-melanotic skin cancer and carcinoma in situ of the cervix.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
Mayo Clinic in Arizona
Scottsdale, Arizona, 85259
About this study
Official title: A Prospective Observational Study of Proton Stereotactic Body Radiation Therapy and Immunotherapy for Recurrent/Progressive Locoregional or Metastatic Head and Neck Cancer
This study observes the clinical efficacy of combining proton SBRT with PD-1 blockade immunotherapy in both the locoregionally recurrent and metastatic settings.
- Conditions
- Head and Neck Cancer
- Being tested
- Proton Stereotactic Body Radiation Therapy (SBRT) (5 fractions; 3500-4500 cGy), Proton Stereotactic Body Radiation Therapy (SBRT) (3-5 fractions; various dose and fractionation regimens depending on treatment site)., Nivolumab 3 mg/kg IV q2 weeks, Proton or Photon SBRT (3-5 fractions; various dose and fractionation regimens depending on treatment site).
- Medical subject headings
- Head and Neck Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Proton Stereotactic Body Radiation Therapy (SBRT) (5 fractions; 3500-4500 cGy)Radiation
Patients will be receiving proton SBRT
Proton Stereotactic Body Radiation Therapy (SBRT) (3-5 fractions; various dose and fractionation regimens depending on treatment site).Radiation
Patients will receive proton SBRT.
Nivolumab 3 mg/kg IV q2 weeksDrug
Patients will receive Nivolumab x2 cycles before SBRT q2 weeks, and continued q2 weeks after SBRT until progression or at the discretion of the treating physician.
Proton or Photon SBRT (3-5 fractions; various dose and fractionation regimens depending on treatment site).Radiation
Patients with further oligoprogression (5 or fewer sites) will be eligible to receive additional SBRT to all sites of oligoprogression.
| Study group | Role | What they receive |
|---|---|---|
| Locoregional | Patients with recurrent locoregional head and neck cancer Receives: Radiation: Proton Stereotactic Body Radiation Therapy (SBRT) (5 fractions; 3500-4500 cGy); Drug: Nivolumab 3 mg/kg IV q2 weeks; Radiation: Proton or Photon SBRT (3-5 fractions; various dose and fractionation regimens depending on treatment site). | |
| Metastatic | Patients with recurrent metastatic head and neck cancer Receives: Radiation: Proton Stereotactic Body Radiation Therapy (SBRT) (3-5 fractions; various dose and fractionation regimens depending on treatment site).; Drug: Nivolumab 3 mg/kg IV q2 weeks; Radiation: Proton or Photon SBRT (3-5 fractions; various dose and fractionation regimens depending on treatment site). |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective response rate (ORR) using iRECIST 1.1 criteria for locoregional arm
ORR is defined as the proportion of patients who achieved a best response of complete response (CR) or partial response (PR) using iRECIST 1.1 criteria, and will be evaluated for both the lesion(s) treated with SBRT, referred to as "Target lesion (+SBRT+Nivo), as well as the lesion(s) not treated with SBRT (if applicable), referred to as "Target lesion (+Nivo only)", per the prescribed treatment. The primary endpoint for the locoregional arm will be considered met if the assumption and desired outcome are achieved for ORR in the "Target lesion(s) (+SBRT+Nivo)". Best overall response (BOR) is defined as the best response designation, recorded between the start date of immunotherapy and the date of progression using iRECIST 1.1 criteria.
Measured: From start date of immunotherapy to disease progression; up to 2 years
Objective response rate (ORR) using iRECIST 1.1 criteria for metastatic arm
ORR is defined as the proportion of patients who achieved a best response of complete response (CR) or partial response (PR) using iRECIST 1.1 criteria, and will be evaluated for both the lesion(s) treated with SBRT, referred to as "Target lesion (+SBRT+Nivo), as well as the lesion(s) not treated with SBRT, referred to as "Target lesion (+Nivo only)", per the prescribed treatment. The primary endpoint for the metastatic arm will be considered met if the assumption and desired outcome are achieved for ORR in the "Target lesion(s) (+Nivo only)" since these are the lesions we hypothesize will have an augmented response from proton SBRT through the abscopal effect. Best overall response (BOR) is defined as the best response designation, recorded between the start date of immunotherapy and the date of progression using iRECIST 1.1 criteria.
Measured: From start date of immunotherapy to disease progression; up to 2 years
Secondary outcomes (10)
Local control rate for both arms
Measured: From start date of immunotherapy to disease local progression; up to 1 year
Overall Survival Time for both arms
Measured: From start date of immunotherapy to date of death, up to 2 years
Overall Survival for both arms
Measured: From start date of immunotherapy to 3, 6, 9, and 12 month
Progression-free survival for both arms
Measured: From start date of immunotherapy to disease progression or death, whichever occurs first; assessed up to 2 years
Time to progression (TTP)
Measured: From start date of immunotherapy to disease progression, but does not count patients who die from other causes; assessed up to 2 years
New development of distant metastasis for both arms
Measured: From start date of immunotherapy to disease progression or death, whichever occurs first; assessed up to 2 years
Quality of Life for both arms
Quality of life will be assessed through questionaire EORTC QLQ-H\&N35
Measured: From start date of immunotherapy (baseline evaluation) to approximately 6 months after enrollment at Day 45, 90, 130, and 170
Quality of Life for both arms
Quality of life will be assessed through questionaire Mayo PRO for Head and Neck
Measured: From start date of immunotherapy (baseline evaluation) to approximately 6 months after enrollment at Day 45, 90, 130, and 170
Adverse Effects for both arms
Measured: From start date of immunotherapy (baseline evaluation) to approximately 6 months after enrollment at Day 45, 90, 130 and 170
Predictive and prognostic biomarkers for both arms
a maximum of 5 blood draws will be used
Measured: Baseline, Day 15-30, 45, 90 and 130
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 May 2018
- Study start3 Jul 2018
- Primary completion6 Jan 2020
- Study completion6 Jan 2020
Why it stopped: Failure to accrue.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Head and Neck CancerStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Daniel J. Ma, MD, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03539198
- Sponsor's protocol ID
- 17-010910
- Other IDs
- ROR1771
- Status last verified
- Nov 2024
- First submitted
- 30 Apr 2018
- Last updated
- 14 Nov 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective Observational Study of Proton Stereotactic Body Radiation Therapy and Immunotherapy for Recurrent/Progressive Locoregional or Metastatic Head and Neck Cancer
- ClinicalTrials.gov ID
- NCT03539198
- Acronym / sponsor ID
- 17-010910
- Conditions
- Head and Neck Cancer
- Study type
- Observational
- Recruitment status
- TerminatedReason stopped: Failure to accrue.
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Study start
- 3 Jul 2018 (actual)
- Primary completion
- 6 Jan 2020 (actual)
- Study completion
- 6 Jan 2020 (actual)
- First posted
- 29 May 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study observes the clinical efficacy of combining proton SBRT with PD-1 blockade immunotherapy in both the locoregionally recurrent and metastatic settings.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Locoregional | – | Radiation: Proton Stereotactic Body Radiation Therapy (SBRT) (5 fractions; 3500-4500 cGy), Drug: Nivolumab 3 mg/kg IV q2 weeks, Radiation: Proton or Photon SBRT (3-5 fractions; various dose and fractionation regimens depending on treatment site).Patients with recurrent locoregional head and neck cancer |
| Metastatic | – | Radiation: Proton Stereotactic Body Radiation Therapy (SBRT) (3-5 fractions; various dose and fractionation regimens depending on treatment site)., Drug: Nivolumab 3 mg/kg IV q2 weeks, Radiation: Proton or Photon SBRT (3-5 fractions; various dose and fractionation regimens depending on treatment site).Patients with recurrent metastatic head and neck cancer |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- patients with locoregional or metastatic head and neck cancers
Key inclusion criteria (24 listed)
- Age ≥18 years old whose multidisciplinary care team has determined that the treatments outlined in the protocol are the treating physicians' equipoised clinical recommendation, the multidisciplinary head \& neck tumor board's recommendation, and that any reasonable alternative treatments have been reviewed with the subject.
- Signed written informed consent in accordance with regulatory and institutional guidelines.
- Must be willing to comply with scheduled visits, treatment schedule, laboratory testing and other study obligations. Patients must be receiving SOC treatment for recurrent or progressive Head and Neck cancer. Please refer to UCM procedural manual.
- Histologically confirmed head and neck squamous cell carcinoma from any of the primary sites: oral cavity, pharynx, larynx, nasopharynx, sinonasal, cutaneous, or unknown head and neck primary.
- Subjects with head and neck squamous cell carcinoma that has progressed during chemotherapy with a platinum-based drug or that has recurred or metastasized after platinum-based chemotherapy or in patients with an intolerance to or contraindication for platinum-based chemotherapy will be eligible.
Key exclusion criteria (9 listed)
- Active brain metastases or leptomeningeal disease. Note: Treated brain metastases (e.g. GammaKnife or surgical resection) are eligible if these have been treated and are without MRI evidence of progression for at least 8 weeks after treatment. MRI must be performed within 35 days prior tobeginning immunotherapy.
- Histologically confirmed non-squamous histologies including salivary gland or other non-squamous histologies (e.g. mucosal melanoma) are not allowed; exception WHO Type I-III nasopharynx, which are allowed.
- Subjects with active autoimmune disease or on steroid therapy of >10 mg/day prednisone or equivalent.
- Subjects who have undergone bone marrow or solid organ transplantation.
- Known HIV, hepatitis B or C infection.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Proton Stereotactic Body Radiation Therapy (SBRT) (5 fractions; 3500-4500 cGy)Patients will be receiving proton SBRT | Radiation | Locoregional |
| Proton Stereotactic Body Radiation Therapy (SBRT) (3-5 fractions; various dose and fractionation regimens depending on treatment site).Patients will receive proton SBRT. | Radiation | Metastatic |
| Nivolumab 3 mg/kg IV q2 weeksPatients will receive Nivolumab x2 cycles before SBRT q2 weeks, and continued q2 weeks after SBRT until progression or at the discretion of the treating physician. | Drug | Locoregional, Metastatic |
| Proton or Photon SBRT (3-5 fractions; various dose and fractionation regimens depending on treatment site).Patients with further oligoprogression (5 or fewer sites) will be eligible to receive additional SBRT to all sites of oligoprogression. | Radiation | Locoregional, Metastatic |
Primary outcome
Objective response rate (ORR) using iRECIST 1.1 criteria for locoregional arm
Time frame: From start date of immunotherapy to disease progression; up to 2 years
ORR is defined as the proportion of patients who achieved a best response of complete response (CR) or partial response (PR) using iRECIST 1.1 criteria, and will be evaluated for both the lesion(s) treated with SBRT, referred to as "Target lesion (+SBRT+Nivo), as well as the lesion(s) not treated with SBRT (if applicable), referred to as "Target lesion (+Nivo only)", per the prescribed treatment. The primary endpoint for the locoregional arm will be considered met if the assumption and desired outcome are achieved for ORR in the "Target lesion(s) (+SBRT+Nivo)". Best overall response (BOR) is defined as the best response designation, recorded between the start date of immunotherapy and the date of progression using iRECIST 1.1 criteria.
Objective response rate (ORR) using iRECIST 1.1 criteria for metastatic arm
Time frame: From start date of immunotherapy to disease progression; up to 2 years
ORR is defined as the proportion of patients who achieved a best response of complete response (CR) or partial response (PR) using iRECIST 1.1 criteria, and will be evaluated for both the lesion(s) treated with SBRT, referred to as "Target lesion (+SBRT+Nivo), as well as the lesion(s) not treated with SBRT, referred to as "Target lesion (+Nivo only)", per the prescribed treatment. The primary endpoint for the metastatic arm will be considered met if the assumption and desired outcome are achieved for ORR in the "Target lesion(s) (+Nivo only)" since these are the lesions we hypothesize will have an augmented response from proton SBRT through the abscopal effect. Best overall response (BOR) is defined as the best response designation, recorded between the start date of immunotherapy and the date of progression using iRECIST 1.1 criteria.
10 secondary outcomes
Local control rate for both arms
Time frame: From start date of immunotherapy to disease local progression; up to 1 year
Overall Survival Time for both arms
Time frame: From start date of immunotherapy to date of death, up to 2 years
Overall Survival for both arms
Time frame: From start date of immunotherapy to 3, 6, 9, and 12 month
Progression-free survival for both arms
Time frame: From start date of immunotherapy to disease progression or death, whichever occurs first; assessed up to 2 years
Time to progression (TTP)
Time frame: From start date of immunotherapy to disease progression, but does not count patients who die from other causes; assessed up to 2 years
New development of distant metastasis for both arms
Time frame: From start date of immunotherapy to disease progression or death, whichever occurs first; assessed up to 2 years
Quality of Life for both arms
Time frame: From start date of immunotherapy (baseline evaluation) to approximately 6 months after enrollment at Day 45, 90, 130, and 170
Quality of Life for both arms
Time frame: From start date of immunotherapy (baseline evaluation) to approximately 6 months after enrollment at Day 45, 90, 130, and 170
Adverse Effects for both arms
Time frame: From start date of immunotherapy (baseline evaluation) to approximately 6 months after enrollment at Day 45, 90, 130 and 170
Predictive and prognostic biomarkers for both arms
Time frame: Baseline, Day 15-30, 45, 90 and 130
Results and safety
The study was stopped early (reason given: Failure to accrue.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Nov 2024.
- Mayo Clinic Clinical TrialsLink provided by the sponsor.
- Individual participant dataSharing planned: No
Related trials for Head and Neck Cancer
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingObservational study
Proton Re-irradiation in Patients With Recurrent or Second Primary Head and Neck Cancer , a Multicentre Phase II Single Arm Trial
Head & Neck Cancer
RecruitingPhase 2/3
Multicenter Validation Trial of [18F]AlF-FAPI-74 for PET Imaging of Cancer-associated Fibroblasts Through Fibroblast Activation Protein Inhibitors (FAPI) in Different Tumor Types
Oesophageal Cancer, Gastric Cancer
RecruitingPhase 2
Proton Spatially Fractionated Radiotherapy or Photon Stereotactic Body Radiotherapy in Combination With Pembrolizumab Before Surgery for the Treatment of Locally Advanced and Radiation-Naive Locoregionally Recurrent Oral Cavity Cancer, OSPRI Trial
Locally Advanced Oral Cavity Squamous Cell Carcinoma, Locally Recurrent Oral Cavity Squamous Cell Carcinoma
RecruitingPhase 4
Lidocaine Infiltration and Neuroimmunomodulation in Head and Neck Cancer Surgery
Head and Neck Cancer (H&N)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Daniel J. Ma, MD principal investigator
Mayo Clinic
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Head and Neck Cancer, run by Mayo Clinic at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 24 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 14 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: Failure to accrue.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective response rate (ORR) using iRECIST 1.1 criteria for locoregional arm (time frame: From start date of immunotherapy to disease progression; up to 2 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Nov 2024.