cancer, malignancy cancer
Conditions
Interventions
The study treatment consists of intravenous administration 4 cycles qw3 of the
combination of nivolumab and ipilumumab, followed by nivolumab qw4. This first
administration of the medication occurs
Sponsors
Universitair Medisch Centrum Utrecht
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Histologically confirmed metastatic or unresectable cancer that progressed under regular treatment options 2. Age >= 18 years. 3. Has signed and dated written informed consent before performing any study procedure, including screening. 4. Anticipated life expectancy >= 12 weeks by Investigator judgement. 5. 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 =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. • 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. 6. Sonication will be performed on tumors that have not previously directly been treated with radiation therapy or surgery unless they showed significant mass regrowth. 7. 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. 8. Performance status of 0 or 1 on the WHO Performance Scale. 9. 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 =60 mL/minute (1.5xULN, except in subjects with Gilbert*s Syndrome 10. Patients must agree to use an adequate method of contraception for the course of the study through 120 days after the last dose of study medication. 11. Patients must be willing to undergo tumor biopsy.
Exclusion criteria
Exclusion criteria: 1. 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 Grade 1 due to a previously administered therapy. Subjects with
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety 1. 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 three months after the last ICI administration. Tolerability 1. PROMS questionnaires: • Customized HIFU-HT-tolerability questionnaire. • EuroQol Group EQ-5D. • Utrecht symptom diary immunotherapy (USD-I). 2. Discontinuation rate due to adverse events. Feasibility 1. The number of technically effective HIFU-HT procedures. 2. The percentage screening failures. 3. Time burden of the study procedures. | — |
Secondary
| Measure | Time frame |
|---|---|
| Radiological response 1. Local response of HIFU-HT treated tumor with a MRI directly and 12 weeks after HIFU-HT 2. 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) Immunologic response 1. Analysis of immunological parameters in peripheral blood samples (plasma and peripheral blood mononuclear cells (PBMCs) 2. Analysis of immune infiltrates in tumor biopsies taken at baseline and 7 days after HIFU-HT Clinical response 1. Explorative analysis to assess progression-free survival and overall survival while taking into consideration the heterogeneous patient population in this basket design. | — |
Countries
Netherlands
Contacts
Public ContactK.P.M. Suijkerbuijk
Universitair Medisch Centrum Utrecht
Outcome results
None listed