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

NCT04021277 | Terminated Phase 1

• 2 other identifiers: PS101-01-20182018-004609-16
• Study Type: interventional
• Target: 11
• Locations: 2 countries
• Sites: 4

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.

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

Outcome Measures

Primary Outcomes (3)

• 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

• 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

• 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 Outcomes (2)

• Preliminary anti-tumor activity at Week 8

  Baseline to Week 8

• Best overall response (Part 1b only)

  Baseline to 24 weeks

Study Arms (2)

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

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

Drug: 20 uL/kg PS101; Drug: 40 uL/kg PS101; Device: Ultrasound

Interventions

20 uL/kg PS101 DRUG

20 uL/kg PS101 and chemotherapy given for 4 cycles over 6 weeks

Part 1a: ACT with chemotherapy in metastatic solid tumours; Part 1b ACT with chemotherapy in metastatic CRC

40 uL/kg PS101 DRUG

40 uL/kg PS101 and chemotherapy given for 4 cycles over 6 weeks

Part 1a: ACT with chemotherapy in metastatic solid tumours; Part 1b ACT with chemotherapy in metastatic CRC

Ultrasound DEVICE

Ultrasound activation and enhancement

Part 1a: ACT with chemotherapy in metastatic solid tumours; Part 1b ACT with chemotherapy in metastatic CRC

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• EXACT Therapeutics AS: lead

Study Sites (4)

Oslo University Hospital HF

Oslo, Norway

Location

Cambridge University Hospitals NHS Foundation Trust, Addenbrookes Hospital

Cambridge, CB20QQ, United Kingdom

Location

Freeman Hospital

Newcastle upon Tyne, NE7 7DN, United Kingdom

Location

Royal Marsden NHS Foundation Trust

Sutton, SM25PT, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 35930441 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

PS-101; Ultrasonography

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: The participant and radiologist are blinded to treatment dose
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: July 3, 2019
• First Posted: July 16, 2019
• Study Start: September 17, 2019
• Primary Completion: August 27, 2024
• Study Completion: September 24, 2024
• Last Updated: October 10, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

GB (3); NO (1)