Solid TumorPhase 1ACTNCT04021277
PS101-mediated ACT With Chemotherapy in Liver Metastases From Cancer of Gastrointestinal Origin
A Phase 1 study testing 20 uL/kg PS101, 40 uL/kg PS101 and Ultrasound in people with Solid Tumor and Colorectal Cancer, run by EXACT Therapeutics AS at 4 sites in 2 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumor, Colorectal Cancer
- What is being tested?
- 20 uL/kg PS101, 40 uL/kg PS101 and Ultrasound
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 4 sitesin 2 countries
- Study dates
- 17 Sep 2019to 24 Sep 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
MAIN INCLUSION CRITERIA
Providing informed consent and able to co-operate with the study requirements.
Diagnosis of any advanced solid tumour with liver metastases suitable for FOLFOX or FOLFIRI chemotherapy (Part 1a) / Diagnosis of any metastatic CRC with liver metastases suitable for FOLFIRI chemotherapy (Part 1b) .
At least two distinct target liver metastases (visible on computed tomography (CT)/magnetic resonance imaging (MRI) and of a suitable size), one being suitable for ultrasound and suitably spaced apart.
Eastern Co-operative Oncology performance status of 0 or 1 and with a predicted meaningful survival of at least 6 months.
. Suitable laboratory test results to receive chemotherapy.
Females who are not pregnant or lactating; males and females willing to follow contraceptive requirements.
Able to receive CT/MRI contrast agents.
MAIN EXCLUSION CRITERIA
Liver metastases suitable for immediate resection (and therefore neoadjuvant therapy unnecessary) or planned to be treated with radio-frequency ablation or other local therapies.
Liver radiotherapy in the last 2 months.
Use of tyrosine kinase inhibitors or monoclonal antibodies that are known to target angiogenesis receptors and/or their ligands.
Persistent, unresolved National Cancer Institute (NCI) common terminology criteria for adverse events (CTCAE) Version 5.0 Grade 2 or higher drug-related toxicity (except alopecia, erectile dysfunction, hot flashes, decreased libido) following previous treatment.
Grade 2 or greater sensory/motor neuropathy.
Inadequate recovery from any prior surgical procedure or major surgical procedure in the last 4 weeks
Serious/symptomatic active infection, or infection requiring antibiotics in the last 7 days, active cholangitis, disease requiring metal biliary stent(s), HIV infection, bleeding diathesis or other medical or psychiatric condition that might interfere with the patient's participation in the trial or results.
Hypersensitivity to any of the components of PS101 (e.g. eggs or egg products).
Hypersensitivity to FOLFOX or FOLFIRI, or previously having to discontinue either due to adverse events.
Participation in any other clinical trials involving therapeutic agents in the last 4 weeks.
History of QT prolongation, clinically significant ventricular tachycardia, ventricular fibrillation, heart block, myocardial infarction within 6 months, congestive heart failure New York Heart Association Class III or IV, unstable angina or any relevant clinical history, signs or symptoms suggestive of clinically significant, uncontrolled cardiovascular or pulmonary disease.
Trial locations and contacts
4 sites in 2 countries.
4 sites in 2 countries
United Kingdom3 sites
Cambridge University Hospitals NHS Foundation Trust, Addenbrookes Hospital
Cambridge, CB20QQ
Freeman Hospital
Newcastle upon Tyne, NE7 7DN
Royal Marsden NHS Foundation Trust
Sutton, SM25PT
About this study
Official title: 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
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.
Read the 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.
- Conditions
- Solid Tumor, Colorectal Cancer
- Being tested
- 20 uL/kg PS101, 40 uL/kg PS101, Ultrasound
- Keywords
- PS101-mediated ACT: the combination of PS101 with ultrasound, PS101-mediated ACT procedure: PS101 and ultrasound, ACT treatment: 3 × PS101-mediated ACT procedures
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
20 uL/kg PS101Drug
20 uL/kg PS101 and chemotherapy given for 4 cycles over 6 weeks
40 uL/kg PS101Drug
40 uL/kg PS101 and chemotherapy given for 4 cycles over 6 weeks
UltrasoundDevice
Ultrasound activation and enhancement
| Study group | Role | What they receive |
|---|---|---|
| Part 1a: ACT with chemotherapy in metastatic solid tumours | Experimental | 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 Receives: Drug: 20 uL/kg PS101; Drug: 40 uL/kg PS101; Device: Ultrasound |
| Part 1b ACT with chemotherapy in metastatic CRC | Experimental | 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 Receives: Drug: 20 uL/kg PS101; Drug: 40 uL/kg PS101; Device: Ultrasound |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability: DLTs (Part 1a only)
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
Measured: 4 weeks from the first ACT treatment in each patient
Number of patients with adverse events
Adverse events are summarised in the adverse event section. An overall summary will be presented here
Measured: From informed consent to 12 weeks from study start
Number of patients with adverse device effects
Number of patients with any AE related to the use of an Investigational Medical Device.
Measured: From the first PS101-mediated ACT procedure to 12 weeks from study start
Secondary outcomes (2)
Preliminary anti-tumor activity at Week 8
Change from baseline in maximum tumor diameter and volume in liver metastases
Measured: Baseline to Week 8
Best overall response (Part 1b only)
Best overall response based on CR, PR, SD, PR according to RECIST Version 1.1
Measured: Baseline to 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jul 2019
- Study start17 Sep 2019
- Primary completion27 Aug 2024
- Study completion24 Sep 2024
Why it stopped: Business reason
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Solid TumorStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Model description
- Part 1 is divided into two stages: Part 1a: 3+3 open label non-randomized design to evaluate two doses Part 1b: Single blind, randomized design to evaluate two doses
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- EXACT Therapeutics AS
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04021277
- Sponsor's protocol ID
- PS101-01-2018
- Other IDs
- 2018-004609-16, 2018
- Acronym
- ACT
- Status last verified
- Oct 2024
- First submitted
- 3 Jul 2019
- Last updated
- 10 Oct 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Fan CH, Ho YJ, Lin CW, Wu N, Chiang PH, Yeh CK. State-of-the-art of ultrasound-triggered drug delivery from ultrasound-responsive drug carriers. Expert Opin Drug Deliv. 2022 Aug;19(8):997-1009. doi: 10.1080/17425247.2022.2110585. Epub 2022 Aug 10.
PubMed 35930441
Study at a glance
From the registry record, last updated by the sponsor on 10 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04021277
- Acronym / sponsor ID
- ACT / PS101-01-2018
- Conditions
- Solid Tumor, Colorectal Cancer
- Keywords
- PS101-mediated ACT: the combination of PS101 with ultrasound, PS101-mediated ACT procedure: PS101 and ultrasound, ACT treatment: 3 × PS101-mediated ACT procedures
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Business reason
- Enrolment
- 11 participants (actual)
- Lead sponsor
- EXACT Therapeutics ASIndustry (pharma, biotech, devices)
- Study start
- 17 Sep 2019 (actual)
- Primary completion
- 27 Aug 2024 (actual)
- Study completion
- 24 Sep 2024 (actual)
- First posted
- 16 Jul 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
- Model description
- Part 1 is divided into two stages: Part 1a: 3+3 open label non-randomized design to evaluate two doses Part 1b: Single blind, randomized design to evaluate two doses
| Arm | Type | Receives |
|---|---|---|
| Part 1a: ACT with chemotherapy in metastatic solid tumours | Experimental | Drug: 20 uL/kg PS101, Drug: 40 uL/kg PS101, Device: Ultrasound20 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 | Experimental | Drug: 20 uL/kg PS101, Drug: 40 uL/kg PS101, Device: Ultrasound20 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 20 uL/kg PS10120 uL/kg PS101 and chemotherapy given for 4 cycles over 6 weeks | Drug | Part 1a: ACT with chemotherapy in metastatic solid tumours, Part 1b ACT with chemotherapy in metastatic CRC |
| 40 uL/kg PS10140 uL/kg PS101 and chemotherapy given for 4 cycles over 6 weeks | Drug | Part 1a: ACT with chemotherapy in metastatic solid tumours, Part 1b ACT with chemotherapy in metastatic CRC |
| UltrasoundUltrasound activation and enhancement | Device | Part 1a: ACT with chemotherapy in metastatic solid tumours, Part 1b ACT with chemotherapy in metastatic CRC |
Primary outcome
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.
2 secondary outcomes
Preliminary anti-tumor activity at Week 8
Time frame: Baseline to Week 8
Best overall response (Part 1b only)
Time frame: Baseline to 24 weeks
Results and safety
The study was stopped early (reason given: Business reason). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Oct 2024.
- Derived from this study: PubMed 35930441Fan CH, Ho YJ, Lin CW, Wu N, Chiang PH, Yeh CK. State-of-the-art of ultrasound-triggered drug delivery from ultrasound-responsive drug carriers. Expert Opin Drug Deliv. 2022 Aug;19(8):997-1009. doi: 10.1080/17425247.2022.2110585. Epub 2022 Aug 10.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
4 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing 20 uL/kg PS101, 40 uL/kg PS101 and Ultrasound in people with Solid Tumor and Colorectal Cancer, run by EXACT Therapeutics AS at 4 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 10 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United Kingdom, Norway. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Business reason). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and tolerability: DLTs (Part 1a only) (time frame: 4 weeks from the first ACT treatment in each patient). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04021277, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Oct 2024.