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Acoustic Cluster Therapy (ACT) With Chemotherapy in Metastatic Liver Metastases of Gastrointestinal Origin (ACT)

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ClinicalTrials.gov Identifier: NCT04021277
Recruitment Status : Recruiting
First Posted : July 16, 2019
Last Update Posted : July 23, 2019
Sponsor:
Information provided by (Responsible Party):
Phoenix Solutions

Brief Summary:
This clinical trial will first aim to test the safety of PS101-mediated Acoustic Cluster Therapy (ACT) in any patient with hepatic metastases in order to identify the recommended dose and schedule that can be taken forward in combination with standard of care chemotherapy, as well as standardising the ultrasound administration and imaging requirements. Following this an expansion part in patients with hepatic metastases from colorectal cancer will be started to test for evidence of ACT efficacy. Based on the emerging data from these patients, if indicated, a cohort of pancreatic ductal adenocarcinoma (PDAC) patients with hepatic metastases will be enrolled.

Condition or disease Intervention/treatment Phase
Solid Tumor Colorectal Cancer Pancreatic Cancer Combination Product: PS101 and Ultra Sound for escalation Combination Product: PS101 and Ultra Sound for expansion Phase 1

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. Acoustic Cluster Therapy (ACT) can potentially increase the uptake of an anticancer agent over the US 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 37 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: PS101 injections and ultrasound insonation given at each session of chemotherapy
Masking: None (Open Label)
Primary Purpose: Treatment
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
Estimated Study Start Date : July 15, 2019
Estimated Primary Completion Date : January 2021
Estimated Study Completion Date : January 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: ACT with chemotherapy in metastatic solid tumours
Part 1: PS101 administered together with standard of care chemotherapy (FOLFOX or FOLFIRI) and US insonation over the targeted liver metastasis in patients with solid tumours
Combination Product: PS101 and Ultra Sound for escalation
Part 1 - dose escalation: PS101 given 3 times in a day + 1 US insonation for PK assessment and then PS101 +US insonation given 3 times on each chemotherapy administration day over a period of 8 weeks
Other Name: ACT

Experimental: ACT with chemotherapy in metastatic CRC
Part 2: PS101 administered together with standard of care chemotherapy (FOLFOX or FOLFIRI) and US insonation over the targeted liver metastasis in patients with metastatic colorectal cancer
Combination Product: PS101 and Ultra Sound for expansion
Part 2: PS101 and US insonation given 3 times on each chemotherapy administration day over a period of 8 weeks
Other Name: ACT

Experimental: ACT with chemotherapy in metastatic PDAC
Part 2: PS101 administered together with standard of care chemotherapy (Gemcitabine and nab-paclitaxel) and US insonation over the targeted liver metastasis in patients with metastatic Pancreatic Duct Adenocarcinoma (PDAC)
Combination Product: PS101 and Ultra Sound for expansion
Part 2: PS101 and US insonation given 3 times on each chemotherapy administration day over a period of 8 weeks
Other Name: ACT




Primary Outcome Measures :
  1. Recommended dose and schedule [ Time Frame: 6 months from study start ]
    Dose Escalation (Part 1): occurrence of dose limiting toxicities (DLTs) in more than one patient out of up to six patients at the same dose level that is considered related to PS101 alone or to the addition of PS101 to chemotherapy

  2. Anti-tumour effect [ Time Frame: 18 months from study start ]
    Expansion (Part 2): Evaluate the anti-tumour effect of PS101 mediated ACT in combination with standard of care chemotherapy (FOLFOX or FOLFIRI) by comparing the changes in the size of the US treated and untreated target liver metastatic lesions at baseline and after treatment completion initially in patient with metastatic colorectal cancer and, if indicated, a cohort of metastatic Pancreatic Duct Adenocarcinoma (PDAC) patients


Secondary Outcome Measures :
  1. Safety and toxicity adverse events [ Time Frame: 18 months from study start ]
    Assessment of adverse events according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0

  2. Safety and toxicity haematology data [ Time Frame: 18 months from study start ]
    Assessment of number and nature of haematology laboratory data

  3. Safety and toxicity biochemistry data [ Time Frame: 18 months from study start ]
    Assessment of number and nature of biochemistry laboratory data

  4. ECGs [ Time Frame: 18 months from study start ]
    Evaluation of 12-lead ECG measures

  5. Effect on tumour vascularity [ Time Frame: 18 months from study start ]
    Assess and describe the effect of the addition of ACT to standard of care chemotherapy on tumour vascularity using Dynamic contrast enhanced (DCE) MRI

  6. Effect on tumour cellularity and necrosis [ Time Frame: 18 months from study start ]
    Assess and describe the effect of the addition of ACT to standard of care chemotherapy on tumour cellularity and necrosis using diffusion weighted MRI (DW-MRI)

  7. Pharmacokinetics of PS101 AUC0∼t [ Time Frame: 6 months from study start ]
    Assess Area under the curve AUC0∼t

  8. Pharmacokinetics of PS101 AUC0∼∞ [ Time Frame: 6 months from study start ]
    Assess Area under the curve AUC0∼∞

  9. Pharmacokinetics of PS101 peak concentration [ Time Frame: 6 months from study start ]
    Assess Maximum (or peak) concentration of PS101 (Cmax)

  10. Pharmacokinetics of PS101 clearance [ Time Frame: 6 months from study start ]
    Assess PS101 clearance (CL)

  11. Pharmacokinetics of PS101 residence time [ Time Frame: 6 months from study start ]
    Assess PS101 Mean residence time (MRT)

  12. Pharmacokinetics of PS101 Tmax [ Time Frame: 6 months from study start ]
    Assess time at which the Cmax is observed (Tmax)

  13. Pharmacokinetics of PS101half-life [ Time Frame: 6 months from study start ]
    Assess PS101 half-life (t1/2)

  14. Pharmacokinetics of PS101trough concentration [ Time Frame: 6 months from study start ]
    Assess Minimum (or trough) concentration of PS101 (Cmin)


Other Outcome Measures:
  1. Effect assessed by elastography [ Time Frame: 18 months from study start ]
    Investigate the effects of ACT treatment on liver metastasis using ultrasound elastography



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Depending on the part of the study specific inclusion criteria will apply:

    • Part 1: Dose escalation: Diagnosis of any advanced solid tumour malignancy with liver metastases who are not eligible to receive the standard of care chemotherapy but for whom FOLFOX or FOLFIRI is considered an appropriate chemotherapy
    • Part 2: Colorectal cancer expansion cohort: Diagnosis of metastatic colorectal cancer with liver metastases that are eligible to receive the standard of care chemotherapy (FOLFOX or FOLFIRI)
    • Part 2: PDAC expansion cohort: Diagnosis of metastatic PDAC with liver metastases that are eligible to receive the standard of care chemotherapy with gemcitabine and nab-paclitaxel (Abraxane®)
    • Parts 1 and 2: Dose escalation and expansion (all patients): At least 2 distinct US detectable target metastatic liver lesions that measure 2 to 6 cm in maximum diameter as measured by CT imaging within 2 weeks before the start of therapy. The two metastatic lesions should be of relatively similar size (within 20% in diameter of the longest axis) separated from each other by at least 3 cm of normal liver parenchyma. At least one of the two metastatic lesions must be in left lobe of the liver.
  2. Male or female and ≥ 18 years of age
  3. ECOG performance status of 0 or 1
  4. Written (signed and dated) informed consent and be capable of cooperating with treatment and follow-up
  5. Adequate haematological, renal, hepatic laboratory requirements to allow treatment with selected standard of care chemotherapy

    Laboratory Requirements - typically within 14 days prior to enrolment: Haemoglobin (Hb) ≥ 9.0 g/dL Absolute neutrophil count ≥ 1.5 x 109/L Platelet count ≥ 100 x 109/L Serum bilirubin ≤ 1.5 x upper limit of normal (ULN) Alanine aminotransferase (ALT) ≤ 5 x (ULN) Aspartate aminotransferase (AST) ≤ 5 x (ULN) Serum creatinine ≤ 1.5 x ULN PT and APTT ≤ 1.25x ULN Albumin ≥ 28g/L

  6. Female subjects of childbearing potential must have negative pregnancy test within 14 days prior to first dose of study drug.
  7. Female subjects of childbearing potential and male subjects whose sexual partners are of childbearing potential must agree to abstain from sexual intercourse or to use an effective method of contraception during the study and up to 6 months after the end of study. Examples of effective methods of contraception include oral or injected contraceptives or double barrier methods such as condom plus spermicide or condom plus diaphragm

Exclusion Criteria:

  1. Patients with liver metastases eligible for immediate surgical resection, for whom neoadjuvant chemotherapy is deemed unnecessary
  2. Patients with suitable metastatic liver lesions that are planned to be treated with radio-frequency ablation or any other liver local therapies within 12 weeks prior to enrolment into the study
  3. Use of tyrosine kinase inhibitors or monoclonal antibodies that are known to target angiogenesis receptors and/or their ligands within 4 weeks of enrolment.
  4. Persistent, unresolved CTCAE v5.0 Grade 2 or higher drug-related toxicity (except alopecia, erectile dysfunction, hot flashes, decreased libido) following previous treatment
  5. Grade 2 or greater sensory/motor neuropathy
  6. Inadequate recovery from any prior surgical procedure or major surgical procedure performed within 4 weeks prior to enrolment
  7. Any other medical or psychiatric condition that, in the opinion of the investigator, might interfere with the subject's participation in the trial or interfere with the interpretation of trial results
  8. Serious/symptomatic active infection, or infection requiring antibiotics, within 7 days prior to enrolment
  9. Disease requiring metal biliary stent(s) (plastic stents allowed)
  10. Presence of active cholangitis.
  11. Known Human Immunodeficiency Virus (HIV) infection or a known HIV-related malignancy
  12. Known bleeding diathesis
  13. Known hypersensitivity to any of the components of PS101 (e.g. eggs) or FOLFOX, FOLFIRI, gemcitabine or nab-paclitaxel (depending on chemotherapy to be used)
  14. Liver radiotherapy within 2 months prior to enrolment.
  15. Inability to comply with the protocol requirements
  16. Participation in any other clinical trials involving therapeutic agents within the last 4 weeks prior to enrolment
  17. Patients with history of QT prolongation, clinically significant VT, VF, heart block, myocardial infarction within 6 months, CHF NYHA Class III or IV, unstable angina
  18. Pregnant or lactating females

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04021277


Contacts
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Contact: Sarah J Arbe-Barnes, PhD +44 203 2913032 sarah.arbe-barnes@phoenixsolutions.no
Contact: Robert M Miller, MD +44 203 2913032 robert.miller@phoenixsolutions.no

Locations
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United Kingdom
The Royal Marsden NHS Foundation Trust Recruiting
Sutton, United Kingdom, SM2 5PT
Contact: Udai Banerji, MD    +44 (0)208 661 3984    Udai.banerji@icr.ac.uk   
Principal Investigator: Udai Banerji, MD         
Sponsors and Collaborators
Phoenix Solutions
Investigators
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Study Director: Per Christian Sontum, PhD Phoenix Solutions

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Responsible Party: Phoenix Solutions
ClinicalTrials.gov Identifier: NCT04021277     History of Changes
Other Study ID Numbers: PS101-01-2018
First Posted: July 16, 2019    Key Record Dates
Last Update Posted: July 23, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Colorectal Neoplasms
Pancreatic Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Endocrine Gland Neoplasms
Pancreatic Diseases
Endocrine System Diseases