Treatment of Cancer With Immune Checkpoint Inhibition Therapy Boosted by High Intensity Focused Ultrasound Histotripsy

NCT06524570 | Recruiting Phase 1 DMC

• 1 other identifier: NL85300.041.23
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief 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 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

Metastatic Cancer; Cancer

Keywords

Metastasized; Unresectable; Progressive after regular treatment

Outcome Measures

Primary Outcomes (8)

• 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.)

  Adverse events will be assessed up to 100 days after the last study treatment

• Tolerability: Discontinuation rate

  Discontinuation rate due to adverse events.

  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).

  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).

  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).

  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.

  Day 8

• Feasibility: Percentage of screening failures

  Feasibility:The percentage screening failures.

  Baseline

• Feasibility: Time burden

  Feasibility: Time burden of the study procedures.

  Through study completion, up to two years after start of study treatment

Secondary Outcomes (5)

• Radiological response: MRI

  Directly after HIFU-HT and 12 weeks after start of treatment

• Radiological response: CT

  12 weeks after start of treatment; every 12 weeks while on treatment up to two years after start therapy

• Immunologic response

  Baseline and days 1, 8, 9, 15, 22, 64

• Overall survival

  Every 12 weeks until 2 years

• Progression free survival

  Every 12 weeks until 2 years

Study Arms (1)

Single arm

EXPERIMENTAL

High-intensity focused ultrasound histotripsy combined with ipilimumab + nivolumab

Device: HIFU-HT; Drug: ICI

Interventions

ICI DRUG

Ipilimumab and nivolumab

Also known as: Immune checkpoint inhibitors

Single arm

HIFU-HT DEVICE

High-Intensify Focused Ultrasound Histotripsy

Single arm

Eligibility Criteria

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

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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.
• 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.
• Pregnancy or lactation.

Sponsors & Collaborators

• UMC Utrecht: lead

Study Sites (1)

University Medical Center Utrecht

Utrecht, Utrecht, Netherlands

RECRUITING

MeSH Terms

Conditions

Neoplasms; Neoplasm Metastasis

Interventions

Immune Checkpoint Inhibitors

Condition Hierarchy (Ancestors)

Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses

Central Study Contacts

Karijn P.M. Suijkerbuijk, Prof.

CONTACT

+31655234706; k.suijkerbuijk@umcutrecht.nl

Emma J. van Dijk, M.D.

CONTACT

e.j.vandijk-9@umcutrecht.nl

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Model Details: Single arm phase 1 trial, monocenter

Study Record Dates

• First Submitted: July 8, 2024
• First Posted: July 29, 2024
• Study Start: July 26, 2024
• Primary Completion (Estimated): August 1, 2030
• Study Completion (Estimated): August 1, 2030
• Last Updated: February 18, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)