PS101-mediated ACT With Chemotherapy in Liver Metastases From Cancer of Gastrointestinal Origin
- Conditions
- Solid TumorColorectal Cancer
- Interventions
- Drug: 20 uL/kg PS101Drug: 40 uL/kg PS101Device: Ultrasound
- Registration Number
- NCT04021277
- Lead Sponsor
- EXACT Therapeutics AS
- Brief Summary
Part 1: This clinical study will first test the safety and initial effect on the tumour of PS101-mediated ACT when given in combination with standard of care chemotherapy in patients with liver metastases (initially those with any solid tumors and then further in patients just with colorectal cancer \[CRC\]) in order to identify the recommended dose and schedule of PS101-mediated ACT that can be taken forward for further testing.
Part 2: Based on the Part 1 results, another part in patients with liver metastases from CRC and pancreatic cancer (if indicated) may take place following a substantial protocol amendment.
This record will focus on Part 1 of the study only and will be updated if Part 2 occurs.
- Detailed Description
The suboptimal delivery of an anticancer agent to the target cancer cells represent a significant problem in many solid tumours, as it compromises the effectiveness of established therapeutics. If the amount of drug that reached any tumour could be increased without changing the amount administered systemically, it should be possible to increase the effectiveness of the treatment without adding to systemic toxicity.
PS101-mediated ACT involves the use of an experimental drug and an experimental device in patients with colon/rectal cancer that has spread to the liver and is given in combination with standard of care chemotherapy. The experimental drug, called PS101, is a liquid containing a mixture of positively and negatively charged microbubbles and microdroplets. It is injected into a vein (blood vessel) and from there follows the blood flow around the body to where the cancerous tumours are found. PS101 is given at the same time as a special type of ultrasound (performed using an ultrasound device) at the place in the liver where the cancerous tumour is found. The combination of PS101 and ultrasound is called Acoustic Cluster Therapy (ACT).
PS101-mediated ACT can potentially increase the uptake of an anticancer agent over the ultrasound targeted area. The preclinical development of PS101-mediated ACT suggests that this therapy may be of meaningful benefit while significant additional toxicity is not anticipated.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 11
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part 1a: ACT with chemotherapy in metastatic solid tumours 40 uL/kg PS101 20 uL/kg or 40 uL/kg PS101 administered together with standard of care chemotherapy (FOLFOX or FOLFIRI) and ultrasound insonation over the targeted liver metastasis in patients with solid tumours Part 1a: ACT with chemotherapy in metastatic solid tumours 20 uL/kg PS101 20 uL/kg or 40 uL/kg PS101 administered together with standard of care chemotherapy (FOLFOX or FOLFIRI) and ultrasound insonation over the targeted liver metastasis in patients with solid tumours Part 1b ACT with chemotherapy in metastatic CRC 20 uL/kg PS101 20 uL/kg or 40 uL/kg PS101 administered together with standard of care chemotherapy (FOLFIRI) and ultrasound insonation over the targeted liver metastasis in patients with metastatic colorectal cancer Part 1b ACT with chemotherapy in metastatic CRC 40 uL/kg PS101 20 uL/kg or 40 uL/kg PS101 administered together with standard of care chemotherapy (FOLFIRI) and ultrasound insonation over the targeted liver metastasis in patients with metastatic colorectal cancer Part 1a: ACT with chemotherapy in metastatic solid tumours Ultrasound 20 uL/kg or 40 uL/kg PS101 administered together with standard of care chemotherapy (FOLFOX or FOLFIRI) and ultrasound insonation over the targeted liver metastasis in patients with solid tumours Part 1b ACT with chemotherapy in metastatic CRC Ultrasound 20 uL/kg or 40 uL/kg PS101 administered together with standard of care chemotherapy (FOLFIRI) and ultrasound insonation over the targeted liver metastasis in patients with metastatic colorectal cancer
- Primary Outcome Measures
Name Time Method Safety and tolerability: DLTs (Part 1a only) 4 weeks from the first ACT treatment in each patient Proportion of patients with DLTs related to administration of PS101 IV bolus injection alone (without chemotherapy) or due to the addition of PS101 to FOLFOX or FOLFIRI
Number of patients with adverse events From informed consent to 12 weeks from study start Adverse events are summarised in the adverse event section. An overall summary will be presented here
Number of patients with adverse device effects From the first PS101-mediated ACT procedure to 12 weeks from study start Number of patients with any AE related to the use of an Investigational Medical Device.
- Secondary Outcome Measures
Name Time Method Preliminary anti-tumor activity at Week 8 Baseline to Week 8 Change from baseline in maximum tumor diameter and volume in liver metastases
Best overall response (Part 1b only) Baseline to 24 weeks Best overall response based on CR, PR, SD, PR according to RECIST Version 1.1
Trial Locations
- Locations (4)
Oslo University Hospital HF
🇳🇴Oslo, Norway
Cambridge University Hospitals NHS Foundation Trust, Addenbrookes Hospital
🇬🇧Cambridge, United Kingdom
Freeman Hospital
🇬🇧Newcastle Upon Tyne, United Kingdom
Royal Marsden NHS Foundation Trust
🇬🇧Sutton, United Kingdom