Treatment of cancer with Immune Checkpoint Inhibition therapy boosted by High-Intensity Focused Ultrasound Histotripsy; the iFOCUS study.
- Conditions
- cancermalignancy10027655
- Registration Number
- NL-OMON56837
- Lead Sponsor
- niversitair Medisch Centrum Utrecht
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 24
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 <=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.
• 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 <=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
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.
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
<=10 mg/day or equivalent.
2. 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.
3. Prior chemotherapy, targeted small molecule therapy or monoclonal antibodies
within 4 weeks prior to the first dose of the study treatment.
4. 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.
5. 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.
6. 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.
7. History of other malignancies, except adequately treated and a
cancer-related life-expectancy of more than 5 years.
8. Concurrent medical condition requiring the use of immunosuppressive
medications, or immunosuppressive doses of systemic or absorbable topical
corticosteroids; exceeding prednisolone 10 mg or equivalent.
9. 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.
10. Active infection requiring systemic therapy.
11. History of (non-infectious) pneumonitis that required steroids or current
pneumonitis.
12. Known history of active Tuberculosis.
13. Receipt of a live vaccine within 4 weeks prior to the first dose of the
study treatment.
14. Hypersensitivity to any of the study drugs or their excipients.
15. Contra-indications to MR imaging (e.g. certain pacemakers).
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.
16. Pregnancy or lactation.
17. 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.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Safety 1. Incidence and severity of adverse events (related to HIFU-HT or the<br /><br>combination of HIFU-HT and ICI.) Adverse events will be assessed up to three<br /><br>months after the last ICI administration.<br /><br><br /><br>Tolerability<br /><br>1. PROMS questionnaires:<br /><br>• Customized HIFU-HT-tolerability questionnaire.<br /><br>• EuroQol Group EQ-5D.<br /><br>• Utrecht symptom diary immunotherapy (USD-I).<br /><br>2. Discontinuation rate due to adverse events.<br /><br><br /><br>Feasibility<br /><br>1. The number of technically effective HIFU-HT procedures.<br /><br>2. The percentage screening failures.<br /><br>3. Time burden of the study procedures.</p><br>
- Secondary Outcome Measures
Name Time Method <p>Radiological response<br /><br>1. Local response of HIFU-HT treated tumor with a MRI directly and 12 weeks<br /><br>after HIFU-HT<br /><br>2. Systemic response using RECIST 1.1 as assessed by CT-scan every 12 weeks (or<br /><br>using PERCIST as assessed by PET-CT if not RECIST measurable)<br /><br><br /><br>Immunologic response<br /><br>1. Analysis of immunological parameters in peripheral blood samples (plasma and<br /><br>peripheral blood mononuclear cells (PBMCs)<br /><br>2. Analysis of immune infiltrates in tumor biopsies taken at baseline and 7<br /><br>days after HIFU-HT<br /><br><br /><br>Clinical response<br /><br>1. Explorative analysis to assess progression-free survival and overall<br /><br>survival while taking into consideration the heterogeneous patient population<br /><br>in this basket design.</p><br>