Phase I Trial of the Combination of PS101-Mediated Acoustic Cluster Therapy (ACT) With Chemotherapy for Treatment of Liver Metastasis In Patients With Solid Tumours With an Expansion Cohort in Metastatic Colorectal And Pancreatic Cancer
Trial Snapshot
- Phase
- Phase 1
- Status
- Terminated
- Sponsor
- EXACT Therapeutics AS
- Enrollment
- 11
- Locations
- 4
- Primary Endpoint
- Safety and tolerability: DLTs (Part 1a only)
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Outcomes Assessor)
Masking Description
The participant and radiologist are blinded to treatment dose
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Part 1a: ACT with chemotherapy in metastatic solid tumours
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
Intervention: Ultrasound (Device)
Part 1a: ACT with chemotherapy in metastatic solid tumours
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
Intervention: 20 uL/kg PS101 (Drug)
Part 1a: ACT with chemotherapy in metastatic solid tumours
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
Intervention: 40 uL/kg PS101 (Drug)
Part 1b ACT with chemotherapy in metastatic CRC
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
Intervention: 20 uL/kg PS101 (Drug)
Part 1b ACT with chemotherapy in metastatic CRC
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
Intervention: 40 uL/kg PS101 (Drug)
Part 1b ACT with chemotherapy in metastatic CRC
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
Intervention: Ultrasound (Device)
Outcomes
Primary Outcomes
Safety and tolerability: DLTs (Part 1a only)
Time Frame: 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
Time Frame: 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
Time Frame: 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 Outcomes
- Preliminary anti-tumor activity at Week 8(Baseline to Week 8)
- Best overall response (Part 1b only)(Baseline to 24 weeks)