Treatment of Cancer With Immune Checkpoint Inhibition Therapy Boosted by High Intensity Focused Ultrasound Histotripsy
NCT Number: NCT06524570
Acronym: iFOCUS
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE1
Conditions: Cancer|Metastatic Cancer
Interventions: DEVICE: HIFU-HT|DRUG: ICI
Sponsor: UMC Utrecht
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 24
Study Design: Allocation: NA|Intervention Model: SINGLE_GROUP|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-07-26
Completion Date: 2030-08-01
Locations: University Medical Center Utrecht, Utrecht, Netherlands

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.

Primary Outcome Measures: 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 Outcome Measures: Radiological response: MRI, Local response of HIFU-HT treated tumor as assessed by MRI directly and 12 weeks after HIFU-HT, 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), 12 weeks after start of treatment; every 12 weeks while on treatment up to two years after start therapy|Immunologic response, 1. Analysis of immunological parameters in peripheral blood
2. Analysis of immune infiltrates in tumor biopsies taken at baseline and 7 days after HIFU-HT, 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., 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., Every 12 weeks until 2 years