CancerPhase 1iFOCUSNCT06524570
Treatment of Cancer With Immune Checkpoint Inhibition Therapy Boosted by High Intensity Focused Ultrasound Histotripsy
A Phase 1 study testing HIFU-HT and ICI in people with Cancer and Metastatic Cancer, run by UMC Utrecht at 1 site in Netherlands.
Trial summary
This phase 1 clinical trial aims to evaluate the safety, tolerability and feasibility of combination treatment of High Intensity Focused Ultrasound Histotripsy (HIFU-HT) and immune checkpoint inhibitors (ICI) in adult patients with metastatic or unresectable cancer that have progressive disease after regular… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cancer, Metastatic Cancer
- What is being tested?
- HIFU-HT and ICI
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteNetherlands
- Study dates
- 26 Jul 2024to 1 Aug 2030
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
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
Who may be able to join
- Histologically confirmed metastatic or unresectable cancer that progressed under standard of care treatment options.
- Age ≥ 18 years.
- Has signed and dated written informed consent before performing any study procedure, including screening.
- Anticipated life expectancy ≥ 12 weeks by investigator judgement.
- At least one tumor lesion (primary tumor or metastasis) which is amenable to application of high intensity focused ultrasound histotripsy (determined by a radiologist with HIFU-expertise).
- The lesion must have a distance of ≤30 mm to the skin.
Show all 23Show fewer
- At least part of the lesion must have a distance of ≥10 mm to the skin and other vulnerable structures (e.g. large blood vessels). This part should be sufficient to be able to select at least one HT focus in an area of solid tumor.
- Most liver metastases cannot be treated currently (due to their depth, overlying ribs and movement during breathing), some superficial large left-sided and caudally located right-sided liver metastases excepted
- If the target lesion contains cystic or necrotic regions: the solid component should be ≥10 mm in diameter, sufficient to be able to select at least one HIFU-HT focus in an area of solid tumor with ≥10 mm distance to the skin.
- Sonication will be performed on tumors that have not previously directly been treated with radiation therapy or surgery unless they showed significant mass regrowth.
- Measurable disease (at least one lesion besides the HIFU-HT treated lesion) on CT according to RECIST V 1.1 criteria (or on PET-CT according to PERCIST criteria) as assessed by investigator and local radiology review.
- Performance status of 0 or 1 on the WHO Performance Scale.
- Screening laboratory values must meet the following criteria:
- WBC ≥ 2.0x109/L,
- Neutrophils ≥1.5x109/L
- Platelets ≥100 x109/L
- Hemoglobin ≥5.5 mmol/L
- Serum creatinine ≤1.5 x upper limit of normal (ULN) or calculated creatinine clearance ≥60 mL/minute (≤Grade 1)
- Aspartate aminotransferase (AST) ≤2.5 x ULN; alanine aminotransferase (ALT) ≤2.5 x ULN; AST/ALT <5 x ULN if liver involvement
- Serum bilirubin ≤1.5 x ULN or direct bilirubin ≤ULN for subjects with total bilirubin levels >1.5xULN, except in subjects with Gilbert's Syndrome
- Patients must agree to use an adequate method of contraception for the course of the study through 180 days after the last dose of study medication.
- Patients must be willing to undergo tumor biopsy.
- Sufficient proficiency in the Dutch language to provide informed consent or comply with study procedures
Who cannot join
- Presence of known central nervous system, meningeal, or epidural metastatic disease. However, subjects with known brain metastases are allowed if the brain metastases are stable for ≥4 weeks before the first dose of study treatment. Stable is defined as neurological symptoms not present or resolved to baseline, no radiologic evidence of progression, and steroid requirement of prednisone ≤10 mg/day or equivalent.
- Patients currently participating and receiving study therapy or patients who participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks prior to the first dose of the study treatment.
- Prior chemotherapy, targeted small molecule therapy or monoclonal antibodies within 4 weeks prior to the first dose of the study treatment.
- Prior radiotherapy within 8 weeks prior to the first dose of the study treatment. The patient will be excluded from the study if the only targetable lesion has directly been treated with radiation therapy in the past with an exception for lesions that showed massive regrowth.
- Prior surgery or ablative therapy within 4 weeks prior to the first dose of the study treatment. The patient will be excluded from the study if the only targetable lesion has directly been treated with ablative therapy in the past.
- Ongoing adverse events > Grade 1 due to a previously administered therapy. Subjects with ≤ Grade 2 neuropathy, vitiligo, thyroid disorders, hypocortisolism or alopecia of any grade are an exception to this criterion and may qualify for the study.
Show all 17Show fewer
- History of other malignancies, except adequately treated and a cancer-related life-expectancy of more than 5 years.
- Concurrent medical condition requiring the use of immunosuppressive medications, or immunosuppressive doses of systemic or absorbable topical corticosteroids; exceeding prednisolone 10 mg or equivalent.
- Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, high-dose corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- Active infection requiring systemic therapy.
- History of (non-infectious) pneumonitis that required steroids or current pneumonitis.
- Known history of active Tuberculosis.
- Receipt of a live vaccine within 4 weeks prior to the first dose of the study treatment.
- Hypersensitivity to any of the study drugs or their excipients.
- Contra-indications to MR imaging (e.g. certain pacemakers or severe claustrophobia). Contra-indications to gadolinium-based contrast agents are not an exclusion criterion, as a different brand of gadolinium can be used or if necessary the MRI can be performed without contrast.
- Pregnancy or lactation.
- Any other medical or social condition that, in the opinion of the Principal Investigator, might put the subject at risk of harm during the study or might adversely affect the interpretation of the study data.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Emma J. van Dijk, M.D. contact
Netherlands1 site, 1 recruiting
- Recruiting
University Medical Center Utrecht
Utrecht, Utrecht
K.P.M. Suijkerbuijk, Prof.
About this study
Official title: Treatment of Cancer With Immune Checkpoint Inhibition Therapy Boosted by High Intensity Focused Ultrasound Histotripsy; the iFOCUS Study
This phase 1 clinical trial aims to evaluate the safety, tolerability and feasibility of combination treatment of High Intensity Focused Ultrasound Histotripsy (HIFU-HT) and immune checkpoint inhibitors (ICI) in adult patients with metastatic or unresectable cancer that have progressive disease after regular treatment. Patients will undergo one single session of HIFU-HT during treatment with ipilimumab and nivolumab. Safety, tolerability and feasibility endpoints will be studied as well as radiologic, immunologic and clinical response.
- Conditions
- Cancer, Metastatic Cancer
- Being tested
- HIFU-HT, ICI
- Keywords
- Metastasized, Unresectable, Progressive after regular treatment
- Medical subject headings
- Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HIFU-HTDevice
High-Intensify Focused Ultrasound Histotripsy
ICIDrug
Also called Immune checkpoint inhibitors
Ipilimumab and nivolumab
| Study group | Role | What they receive |
|---|---|---|
| Single arm | Experimental | High-intensity focused ultrasound histotripsy combined with ipilimumab + nivolumab Receives: Device: HIFU-HT; Drug: ICI |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number and severity of adverse events until 100 days after the last study treatment
Safety: Incidence and severity of adverse events (related to HIFU-HT or the combination of HIFU-HT and ICI.)
Measured: Adverse events will be assessed up to 100 days after the last study treatment
Tolerability: Discontinuation rate
Discontinuation rate due to adverse events.
Measured: At every visit untill 2 years after first study treatment
Tolerability: Patient reported tolerability by HIFU-HT-tolerability questionnaire
The HIFU-HT tolerability questionnaire is a self-reported, customized questionnaire that describes the burden/complaints a respondent experienced following HIFU-histotripsy treatment. The questionnaire comprises questions about pain, use of pain medication, complaints other than pain, burden of MRI scan, burden of peri-procedural analgesia, time burden of treatment. Respondents are asked to grade the experienced complaints or burden on a scale of 5 options, ranging from no complaints/no burden to severe complaints/severe burden. If respondents report pain, they are asked to grade their pain on a scale ranging from 0 - 10 (0 reflecting no pain, 10 reflecting worst possible pain) and respondents are asked for how many days the pain was present (ranging from 0 to 7 days).
Measured: Day 8 + 15
Tolerability: Patient reported tolerability by EQ-5D
The EuroQol Group EQ-5D questionnaire (Dutch version) is a self-reported questionnaire that reflects a respondent's health. The EQ-5D comprises questions on 5 domains (mobility, self care, daily activities, pain/complaints, mood), for each of these domains respondents state whether they have no problems, some problems or severe problems. Respondents are also asked to grade their general health status on a scale of 0 - 100 (0 reflecting the worst possible health status, 100 reflecting the best possible health status).
Measured: Baseline, days 1, 8, 15, 22, 43, 64, 91; thereafter every 4 to 8 weeks until 2 years after start of therapy
Tolerability: Patient reported tolerability by USD-I
The Utrecht symptom diary immunotherapy (USD-I) is a self-reported questionnaire that was developed and validated in the UMC Utrecht to score symptoms patients might experience during/after treatment with checkpoint inhibition therapy. The questionnaire comprises of questions on 19 possible symptoms (apetite, stool pattern, diarrhea, abdominal pain, coughing, eye complaints, skin rash, pruritus, headache, myalgia, arthralgia, paresthesias, pain, sleeping problems). Respondents are asked to grade these symptoms on a scale of 0 - 10 (0 reflecting no problems, 10 reflecting worst possible problem).
Measured: Baseline, days 1, 8, 15, 22, 43, 64, 91; thereafter every 4 weeks until 2 years after start of therapy
Feasibility: Number of technically effective HIFU-HT procedures
Feasibility: The number of technically effective HIFU-HT procedures.
Measured: Day 8
Feasibility: Percentage of screening failures
Feasibility:The percentage screening failures.
Measured: Baseline
Feasibility: Time burden
Feasibility: Time burden of the study procedures.
Measured: Through study completion, up to two years after start of study treatment
Secondary outcomes (5)
Radiological response: MRI
Local response of HIFU-HT treated tumor as assessed by MRI directly and 12 weeks after HIFU-HT
Measured: Directly after HIFU-HT and 12 weeks after start of treatment
Radiological response: CT
Best overall systemic response using RECIST 1.1 as assessed by CT-scan every 12 weeks (or using PERCIST as assessed by PET-CT if not RECIST measurable)
Measured: 12 weeks after start of treatment; every 12 weeks while on treatment up to two years after start therapy
Immunologic response
- Analysis of immunological parameters in peripheral blood
- Analysis of immune infiltrates in tumor biopsies taken at baseline and 7 days after HIFU-HT
Measured: Baseline and days 1, 8, 9, 15, 22, 64
Overall survival
Explorative analysis to assess overall survival in months while taking into consideration the heterogeneous patient population in this basket design.
Measured: Every 12 weeks until 2 years
Progression free survival
Explorative analysis to assess progression-free survival in months while taking into consideration the heterogeneous patient population in this basket design.
Measured: Every 12 weeks until 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jul 2024
- Study start26 Jul 2024
- Primary completion1 Aug 2030 (estimated)
- Study completion1 Aug 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CancerStudies of the same condition, open and under way.
- More trials run by UMC UtrechtThe 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
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Single arm phase 1 trial, monocenter
- Masking
- None (open label)
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- UMC Utrecht
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, K.P.M. Suijkerbuijk, UMC Utrecht
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06524570
- Sponsor's protocol ID
- NL85300.041.23
- Acronym
- iFOCUS
- Status last verified
- Jan 2026
- First submitted
- 8 Jul 2024
- Last updated
- 18 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- 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 18 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment of Cancer With Immune Checkpoint Inhibition Therapy Boosted by High Intensity Focused Ultrasound Histotripsy; the iFOCUS Study
- ClinicalTrials.gov ID
- NCT06524570
- Acronym / sponsor ID
- iFOCUS / NL85300.041.23
- Conditions
- Cancer, Metastatic Cancer
- Keywords
- Metastasized, Unresectable, Progressive after regular treatment
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- UMC UtrechtUniversity, hospital or other
- Study start
- 26 Jul 2024 (actual)
- Primary completion
- 1 Aug 2030 (estimated)
- Study completion
- 1 Aug 2030 (estimated)
- First posted
- 29 Jul 2024 (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 phase 1 clinical trial aims to evaluate the safety, tolerability and feasibility of combination treatment of High Intensity Focused Ultrasound Histotripsy (HIFU-HT) and immune checkpoint inhibitors (ICI) in adult patients with metastatic or unresectable cancer that have progressive disease after regular treatment. Patients will undergo one single session of HIFU-HT during treatment with ipilimumab and nivolumab. Safety, tolerability and feasibility endpoints will be studied as well as radiologic, immunologic and clinical response.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Single arm phase 1 trial, monocenter
| Arm | Type | Receives |
|---|---|---|
| Single arm | Experimental | Device: HIFU-HT, Drug: ICIHigh-intensity focused ultrasound histotripsy combined with ipilimumab + nivolumab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- Histologically confirmed metastatic or unresectable cancer that progressed under standard of care treatment options.
- Age ≥ 18 years.
- Has signed and dated written informed consent before performing any study procedure, including screening.
- Anticipated life expectancy ≥ 12 weeks by investigator judgement.
- At least one tumor lesion (primary tumor or metastasis) which is amenable to application of high intensity focused ultrasound histotripsy (determined by a radiologist with HIFU-expertise).
Key exclusion criteria (17 listed)
- Presence of known central nervous system, meningeal, or epidural metastatic disease. However, subjects with known brain metastases are allowed if the brain metastases are stable for ≥4 weeks before the first dose of study treatment. Stable is defined as neurological symptoms not present or resolved to baseline, no radiologic evidence of progression, and steroid requirement of prednisone ≤10 mg/day or equivalent.
- Patients currently participating and receiving study therapy or patients who participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks prior to the first dose of the study treatment.
- Prior chemotherapy, targeted small molecule therapy or monoclonal antibodies within 4 weeks prior to the first dose of the study treatment.
- Prior radiotherapy within 8 weeks prior to the first dose of the study treatment. The patient will be excluded from the study if the only targetable lesion has directly been treated with radiation therapy in the past with an exception for lesions that showed massive regrowth.
- Prior surgery or ablative therapy within 4 weeks prior to the first dose of the study treatment. The patient will be excluded from the study if the only targetable lesion has directly been treated with ablative therapy in the past.
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 |
|---|---|---|
| HIFU-HTHigh-Intensify Focused Ultrasound Histotripsy | Device | Single arm |
| ICIAlso: Immune checkpoint inhibitorsIpilimumab and nivolumab | Drug | Single arm |
Primary outcome
Number and severity of adverse events until 100 days after the last study treatment
Time frame: Adverse events will be assessed up to 100 days after the last study treatment
Safety: Incidence and severity of adverse events (related to HIFU-HT or the combination of HIFU-HT and ICI.)
Tolerability: Discontinuation rate
Time frame: At every visit untill 2 years after first study treatment
Discontinuation rate due to adverse events.
Tolerability: Patient reported tolerability by HIFU-HT-tolerability questionnaire
Time frame: Day 8 + 15
The HIFU-HT tolerability questionnaire is a self-reported, customized questionnaire that describes the burden/complaints a respondent experienced following HIFU-histotripsy treatment. The questionnaire comprises questions about pain, use of pain medication, complaints other than pain, burden of MRI scan, burden of peri-procedural analgesia, time burden of treatment. Respondents are asked to grade the experienced complaints or burden on a scale of 5 options, ranging from no complaints/no burden to severe complaints/severe burden. If respondents report pain, they are asked to grade their pain on a scale ranging from 0 - 10 (0 reflecting no pain, 10 reflecting worst possible pain) and respondents are asked for how many days the pain was present (ranging from 0 to 7 days).
Tolerability: Patient reported tolerability by EQ-5D
Time frame: Baseline, days 1, 8, 15, 22, 43, 64, 91; thereafter every 4 to 8 weeks until 2 years after start of therapy
The EuroQol Group EQ-5D questionnaire (Dutch version) is a self-reported questionnaire that reflects a respondent's health. The EQ-5D comprises questions on 5 domains (mobility, self care, daily activities, pain/complaints, mood), for each of these domains respondents state whether they have no problems, some problems or severe problems. Respondents are also asked to grade their general health status on a scale of 0 - 100 (0 reflecting the worst possible health status, 100 reflecting the best possible health status).
Tolerability: Patient reported tolerability by USD-I
Time frame: Baseline, days 1, 8, 15, 22, 43, 64, 91; thereafter every 4 weeks until 2 years after start of therapy
The Utrecht symptom diary immunotherapy (USD-I) is a self-reported questionnaire that was developed and validated in the UMC Utrecht to score symptoms patients might experience during/after treatment with checkpoint inhibition therapy. The questionnaire comprises of questions on 19 possible symptoms (apetite, stool pattern, diarrhea, abdominal pain, coughing, eye complaints, skin rash, pruritus, headache, myalgia, arthralgia, paresthesias, pain, sleeping problems). Respondents are asked to grade these symptoms on a scale of 0 - 10 (0 reflecting no problems, 10 reflecting worst possible problem).
Feasibility: Number of technically effective HIFU-HT procedures
Time frame: Day 8
Feasibility: The number of technically effective HIFU-HT procedures.
Feasibility: Percentage of screening failures
Time frame: Baseline
Feasibility:The percentage screening failures.
Feasibility: Time burden
Time frame: Through study completion, up to two years after start of study treatment
Feasibility: Time burden of the study procedures.
5 secondary outcomes
Radiological response: MRI
Time frame: Directly after HIFU-HT and 12 weeks after start of treatment
Radiological response: CT
Time frame: 12 weeks after start of treatment; every 12 weeks while on treatment up to two years after start therapy
Immunologic response
Time frame: Baseline and days 1, 8, 9, 15, 22, 64
Overall survival
Time frame: Every 12 weeks until 2 years
Progression free survival
Time frame: Every 12 weeks until 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Feb 2026.
- Individual participant dataSharing planned: No
Related trials for Cancer
Not yet recruitingPhase 1
Hepatic Artery Infusion of Carfilzomib in Participants With Liver Metastatic Disease Previously Treated With Hepatic Artery Infusion Pump Therapy
Colorectal Neoplasms, Neoplasms
RecruitingPhase 2
Tafasitamab With Acalabrutinib and Venetoclax for the Treatment of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Chronic Lymphocytic Leukemia, Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Active, not recruitingPhase 1/2
Selumetinib in Treating Young Patients With Recurrent or Refractory Low Grade Glioma
Low Grade Glioma, Recurrent Childhood Pilocytic Astrocytoma
Enrolling by invitationPhase 2
A Single-Arm Study of Nimotuzumab Combined With NALIRIFOX as First-Line Treatment for Pancreatic Cancer
Pancreatic Cancer Metastatic
Recruiting
Methylation Profiling in Self-Samples for Identification of (Epi)Genetic Biomarkers for Gynecological Cancers
Gynaecological Cancers, Ovarian Cancer
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.
Emma J. van Dijk, M.D. contact
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing HIFU-HT and ICI in people with Cancer and Metastatic Cancer, run by UMC Utrecht at 1 site in Netherlands.
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 23 inclusion and 17 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: looking for participants now, as of the sponsor's last update on 18 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. 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.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Karijn P.M. Suijkerbuijk, Prof. (+31655234706, k.suijkerbuijk@umcutrecht.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number and severity of adverse events until 100 days after the last study treatment (time frame: Adverse events will be assessed up to 100 days after the last study treatment). The study lists 8 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 18 Feb 2026.