Chief Investigator: 

Sponsor: University of Oxford
EudraCT number: 2014-000514-61

A Proof of Concept Study to Investigate the Feasibility of Targeted Release of Doxorubicin from Lyso-thermosensitive Liposomal (LTSL) Doxorubicin (ThermoDox®) Using Focused Ultrasound in Patients with Primary or Secondary Liver Tumours.

Phase 1 prospective non-randomised safety cohort study with all patients recruited from a single UK site (Oxford). The study has an open label design with all participants receiving ThermoDox® and HIFU. The study is split into two parts. Part I is required to identify optimal HIFU exposure parameters using real time thermometry data from an implanted thermistor. Part II does not require thermistor implantation and is designed to more accurately reflect how the therapy would be implemented in clinical practice. All evaluable participants from both Part I and Part II will be included in the endpoint analysis.

Study Status

Open to recruitment.

Target recruitment: 28 Evaluable patients
Recruiting site: Churchill Hospital - Oxford University Hospitals NHS Trust

Inclusion Criteria

Patients will only be eligible for inclusion in this study if all of the following criteria apply:

  1. Pathologically confirmed advanced solid tumour with liver metastasis suitable for intervention (as assessed by ultrasound or other radiological methods). In addition confirmed primary liver tumours (hepatocellular carcinoma or cholangiocarcinoma) can be included.
  2. Will have progressed or remained stable on conventional chemotherapy.
  3. Male or Female, Age ≥ 18 years.
  4. Have life expectancy of ≥ 3 months.
  5. Left Ventricular Ejection Fraction (LVEF) ≥ 50% on echocardiogram.
  6. Have not received radiotherapy to the target area within the preceding 12 months.
  7. A World Health Organisation (WHO) performance status of ≤ 1 (Appendix 1).
  8. Able and willing to give written informed consent, indicating that they are aware of the investigational nature of this study and potential risks, and able to comply with the protocol for the duration of the study, including scheduled follow-up visits and examinations.

Exclusion Criteria

  1. Have surgery or other procedure requiring general anaesthesia planned to be undertaken during the period of the study.
  2. Have serious illnesses including, but not limited to, congestive heart failure (NYHA class III or IV functional classification); life threatening cardiac arrhythmia; or myocardial infarction or cerebral vascular accident within the last 6 months.
  3. Have on going significant infection (chest, urine, blood, intra-abdominal).
  4. Have uncontrolled diabetes.
  5. Have received a life-time dose of doxorubicin > 450 mg/m2 or a life-time dose of epirubicin > 900 mg/m2 or any dose of both.
  6. Pregnant or breast-feeding. In women of childbearing potential, a negative pregnancy test (serum) is required within 30 days prior to study intervention.
  7. Female participants of child bearing potential and male participants whose partner is of child bearing  potential who are not willing to practice an acceptable form of contraception (i.e. oral contraceptive, diaphragm, cervical cap, condom, surgical sterility) during the study and for 6 months thereafter. Women whose partner has or men who have undergone a vasectomy must use a second form of birth control.
  8. Have any known allergic reactions to any of the drugs or liposomal components or intravenous imaging agents to be used in this study.
  9. Have portal or hepatic vein tumour invasion/thrombosis.
  10. Inadequate Haematological and Biochemical indices:
  11. Have contraindications to receiving doxorubicin including prior sensitivity (rash, dyspnoea, wheezing, urticarial or other symptoms) attributed to anthracyclines or other liposomal drugs.
  12. Use of chemotherapy or of an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the intervention.
  13. Have medically significant active infection.
  14. Have Child-Pugh Class C liver disease, or Class A-B with encephalopathy and/or refractory ascites (Appendix 3).
  15. Documented HIV positive.
  16. Documented diagnosis of haemochromatosis.
  17. Documented history of contrast-induced nephropathy.
  18. Have any of the following contraindications for liver biopsy:
    1. Tense ascites
    2. Suspected liver haemangioma or other vascular tumour
    3. Extra-hepatic biliary obstruction
    4. Known cystic liver disease
  19. Other medical or psychiatric conditions or laboratory abnormalities that the investigator considers would make the patient a poor trial candidate.

Primary Objectives

To determine whether targeted release of doxorubicin from ThermoDox® (‘drug’) using mild hyperthermia generated non-invasively by focused ultrasound (HIFU) is feasible in cancer patients.

Key Dates

Planned accrual completion: Mar 2017
Trial duration: 3 years

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