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

Colorectal Cancer Clinical Trial

— ACT  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04021277
• Other study ID #: PS101-01-2018
• Secondary ID: 2018-004609-16
• Status: Recruiting
• Phase: Phase 1
• Start date: September 17, 2019
• Est. completion date: June 2024

Study information

• Verified date: December 2023
• Source: EXACT Therapeutics AS
• Contact: Clinical Trials Coordinator
• Phone: +47 46 86 39 89
• Email: clinical.trials[@]exact-tx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 32
• Est. completion date: June 2024
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms
• Solid Tumor

Intervention

Drug:
• 20 uL/kg PS101
20 uL/kg PS101 and chemotherapy given for 4 cycles over 6 weeks
• 40 uL/kg PS101
40 uL/kg PS101 and chemotherapy given for 4 cycles over 6 weeks

Device:
• Ultrasound
Ultrasound activation and enhancement

Locations

Country	Name	City	State
Norway	Oslo University Hospital HF	Oslo
United Kingdom	Cambridge University Hospitals NHS Foundation Trust, Addenbrookes Hospital	Cambridge
United Kingdom	Freeman Hospital	Newcastle Upon Tyne
United Kingdom	Royal Marsden NHS Foundation Trust	Sutton

Sponsors (1)

Lead Sponsor	Collaborator
EXACT Therapeutics AS

Countries where clinical trial is conducted

Norway,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	4 weeks from the first ACT treatment in each patient
Primary	Number of patients with adverse events	Adverse events are summarised in the adverse event section. An overall summary will be presented here	From informed consent to 12 weeks from study start
Primary	Number of patients with adverse device effects	Number of patients with any AE related to the use of an Investigational Medical Device.	From the first PS101-mediated ACT procedure to 12 weeks from study start
Secondary	Preliminary anti-tumor activity at Week 8	Change from baseline in maximum tumor diameter and volume in liver metastases	Baseline to Week 8
Secondary	Best overall response (Part 1b only)	Best overall response based on CR, PR, SD, PR according to RECIST Version 1.1	Baseline to 24 weeks