Treatment of Cancer With Immune Checkpoint Inhibition Therapy Boosted by High Intensity Focused Ultrasound Histotripsy
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorUMC Utrecht
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
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.
Trial design
Design model
Single group
Treatments tested in this trial
HIFU-HT
DeviceHigh-Intensify Focused Ultrasound Histotripsy
ICI
DrugIpilimumab and nivolumab
Treatment groups
24 Participants
are divided into 1 treatment groupGroup A: Single armExperimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
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.)
Time frame
Adverse events will be assessed up to 100 days after the last study treatment2
Tolerability: Discontinuation rate
Discontinuation rate due to adverse events.
Time frame
At every visit untill 2 years after first study treatment3
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).
Time frame
Day 8 + 154
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).
Time frame
Baseline, days 1, 8, 15, 22, 43, 64, 91; thereafter every 4 to 8 weeks until 2 years after start of therapySecondary outcomes
1
Radiological response: MRI
Local response of HIFU-HT treated tumor as assessed by MRI directly and 12 weeks after HIFU-HT
Time frame
Directly after HIFU-HT and 12 weeks after start of treatment2
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)
Time frame
12 weeks after start of treatment; every 12 weeks while on treatment up to two years after start therapy3
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
Time frame
Baseline and days 1, 8, 9, 15, 22, 644
Overall survival
Explorative analysis to assess overall survival in months while taking into consideration the heterogeneous patient population in this basket design.
Time frame
Every 12 weeks until 2 yearsSponsors and contacts
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Source ClinicalTrials.gov