PS101-mediated ACT With Chemotherapy in Liver Metastases From Cancer of Gastrointestinal Origin (ACT)

This is an interventional treatment trial for Solid Tumor focused on measuring PS101-mediated ACT: the combination of PS101 with ultrasound, PS101-mediated ACT procedure: PS101 and ultrasound, ACT treatment: 3 × PS101-mediated ACT procedures Read More

Inclusion Criteria:

1. Depending on the part of the study specific inclusion criteria will apply:

   • Part 1: Dose escalation: Diagnosis of any advanced solid tumour malignancy with liver metastases who are not eligible to receive the standard of care chemotherapy but for whom FOLFOX or FOLFIRI is considered an appropriate chemotherapy
   • Part 2: Colorectal cancer expansion cohort: Diagnosis of metastatic colorectal cancer with liver metastases that are eligible to receive the standard of care chemotherapy (FOLFOX or FOLFIRI)
   • Part 2: PDAC expansion cohort: Diagnosis of metastatic PDAC with liver metastases that are eligible to receive the standard of care chemotherapy with gemcitabine and nab-paclitaxel (Abraxane®)
   • Parts 1 and 2: Dose escalation and expansion (all patients): At least 2 distinct US detectable target metastatic liver lesions that measure 2 to 6 cm in maximum diameter as measured by CT imaging within 2 weeks before the start of therapy. The two metastatic lesions should be of relatively similar size (within 20% in diameter of the longest axis) separated from each other by at least 3 cm of normal liver parenchyma. At least one of the two metastatic lesions must be in left lobe of the liver.
2. Male or female and ≥ 18 years of age
3. ECOG performance status of 0 or 1
4. Written (signed and dated) informed consent and be capable of cooperating with treatment and follow-up

5. Adequate haematological, renal, hepatic laboratory requirements to allow treatment with selected standard of care chemotherapy

   Laboratory Requirements - typically within 14 days prior to enrolment: Haemoglobin (Hb) ≥ 9.0 g/dL Absolute neutrophil count ≥ 1.5 x 109/L Platelet count ≥ 100 x 109/L Serum bilirubin ≤ 1.5 x upper limit of normal (ULN) Alanine aminotransferase (ALT) ≤ 5 x (ULN) Aspartate aminotransferase (AST) ≤ 5 x (ULN) Serum creatinine ≤ 1.5 x ULN PT and APTT ≤ 1.25x ULN Albumin ≥ 28g/L

6. Female subjects of childbearing potential must have negative pregnancy test within 14 days prior to first dose of study drug.
7. Female subjects of childbearing potential and male subjects whose sexual partners are of childbearing potential must agree to abstain from sexual intercourse or to use an effective method of contraception during the study and up to 6 months after the end of study. Examples of effective methods of contraception include oral or injected contraceptives or double barrier methods such as condom plus spermicide or condom plus diaphragm

Exclusion Criteria:

1. Patients with liver metastases eligible for immediate surgical resection, for whom neoadjuvant chemotherapy is deemed unnecessary
2. Patients with suitable metastatic liver lesions that are planned to be treated with radio-frequency ablation or any other liver local therapies within 12 weeks prior to enrolment into the study
3. Use of tyrosine kinase inhibitors or monoclonal antibodies that are known to target angiogenesis receptors and/or their ligands within 4 weeks of enrolment.
4. Persistent, unresolved CTCAE v5.0 Grade 2 or higher drug-related toxicity (except alopecia, erectile dysfunction, hot flashes, decreased libido) following previous treatment
5. Grade 2 or greater sensory/motor neuropathy
6. Inadequate recovery from any prior surgical procedure or major surgical procedure performed within 4 weeks prior to enrolment
7. Any other medical or psychiatric condition that, in the opinion of the investigator, might interfere with the subject's participation in the trial or interfere with the interpretation of trial results
8. Serious/symptomatic active infection, or infection requiring antibiotics, within 7 days prior to enrolment
9. Disease requiring metal biliary stent(s) (plastic stents allowed)
10. Presence of active cholangitis.
11. Known Human Immunodeficiency Virus (HIV) infection or a known HIV-related malignancy
12. Known bleeding diathesis
13. Known hypersensitivity to any of the components of PS101 (e.g. eggs) or FOLFOX, FOLFIRI, gemcitabine or nab-paclitaxel (depending on chemotherapy to be used)
14. Liver radiotherapy within 2 months prior to enrolment.
15. Inability to comply with the protocol requirements
16. Participation in any other clinical trials involving therapeutic agents within the last 4 weeks prior to enrolment
17. Patients with history of QT prolongation, clinically significant VT, VF, heart block, myocardial infarction within 6 months, CHF NYHA Class III or IV, unstable angina
18. Pregnant or lactating females