PanDox: Targeted Doxorubicin in Pancreatic Tumours

NCT04852367 | Withdrawn Phase 1

• 1 other identifier: OCTO_095
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This study will combine focused ultrasound to generate heat, and a heat-sensitive chemotherapy drug (ThermoDox®), delivered into the blood of participants with non-resectable pancreatic cancer. We will compare this to standard delivery of chemotherapy - the drug Doxorubicin given into the blood without the addition of ultrasound. We aim to determine whether the novel approach to delivering chemotherapy with heating the tumour by focused ultrasound can enhance the amount of drug delivered to pancreatic tumours. This will be measured by analysing a biopsy sample of treated tumour.

Conditions

Pancreatic Ductal Adenocarcinoma; Pancreatic Cancer Stage IV; Pancreatic Cancer Non-resectable; Pancreatic Cancer Metastatic

Keywords

Focused ultrasound; Doxorubicin; Thermodox; Thermosensitive Liposome; Drug delivery

Outcome Measures

Primary Outcomes (1)

• To quantify the enhancement in intratumoural doxorubicin concentration when delivered with ThermoDox® and mild hyperthermia generated non-invasively by focused ultrasound (FUS) compared to free drug alone

  A statistically significant enhancement in concentration of total intra-tumoural doxorubicin from tumour biopsies at the targeted tumour site receiving drug with FUS compared to drug alone. Quantification of inter-tumoural drug release will be achieved using a GLP HPLC (High Pressure Liquid Chromatography) assay

  within 30 hours of intervention

Secondary Outcomes (3)

• Number of adverse events related to ThermoDox® and FUS compared to free drug alone

  for 21 days post intervention

• Change in radiologically-assessed tumour activity in patients treated with ThermoDox® and FUS, compared to free drug alone

  Pre-treatment, and 14 days post treatment

• Change in patient symptom scores in patients with pancreatic cancer treated with of ThermoDox® and FUS compared to those treated with doxorubicin

  Pre-treatment, within 30 hours post treatment, 14 days and 21 days post treatment

Other Outcomes (1)

• To assess effects of ThermoDox® and FUS treatment compared to free drug alone on pancreatic tumour biomarkers

  Taken pre-treatment and 21 days post-treatment

Study Arms (2)

Arm A (Doxorubicin)

ACTIVE COMPARATOR

a single intravenous dose of Doxorubicin, 50 mg/ m2 in 250 mL of normal saline or 5% dextrose over a 30-min infusion is delivered as per local practice.

Drug: Doxorubicin

Arm B (ThermoDox + Focused Ultrasound)

EXPERIMENTAL

under general anaesthetic, patients receive FUS, which is moved through the target tumour volume to raise the bulk tumour temperature above the thermal release threshold. At presumed target temperature, a single intravenous dose of ThermoDox®, 50 mg/ m2 in 250 mL of normal saline or 5% dextrose over a 30-min infusion is delivered concurrently to FUS, in line with the pharmacy manual provided by the manufacturer. FUS will continue following infusion, for no longer than two hours from infusion commencing.

Device: Focused Ultrasound; Drug: ThermoDox

Interventions

Focused Ultrasound DEVICE

Focused ultrasound targetting the tumour at subablative powers, to facilitate drug release

Arm B (ThermoDox + Focused Ultrasound)

Doxorubicin DRUG

Doxorubicin infusion

Arm A (Doxorubicin)

ThermoDox DRUG

ThermoDox infusion

Arm B (ThermoDox + Focused Ultrasound)

Eligibility Criteria

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

You may qualify if:

• Able to give informed consent prior to any screening procedures being performed and is able and willing to comply with the protocol and its requirements.
• Male or Female, aged 18 years or above.
• Prior histological confirmation of pancreatic adenocarcinoma
• Non-resectable or metastatic (stage IV)
• The primary pancreatic lesion measuring at least 1.5cm minimum diameter and amenable to EUS biopsy sampling
• ECOG performance status 0-1 (Appendix 1)
• Left ventricular ejection fraction (LVEF) ≥ 50% as determined by echocardiogram
• Willing to allow his or her General Practitioner and Consultant, if appropriate, to be notified of participation in the trial.
• Life expectancy of at least 3 months
• Female participants of child bearing potential and male participants whose partner is of child bearing potential must be willing to ensure that they or their partner use highly effective contraception during the trial and for 6 months thereafter.
• Participant has clinically acceptable laboratory results during screening window:
• Lab Test Value required Haemoglobin (Hb) (transfusion to achieve this allowed) ≥ 9g/dL Neutrophils ≥ 1.5 109/L Platelet count ≥ 100 109/L ALT ≤ 2.5 x ULN Alkaline phosphatase ≤ 5 x ULN Serum Bilirubin (stenting to achieve this allowed) ≤ 1.5 x ULN Creatinine Clearance (Calculated by Cockcroft-Gault criteria) ≥ 50ml/min INR \<1.5 unless taking oral anticoagulant (this to be stopped at least 1 week prior to biopsy, at which point this INR limit will then apply)

You may not qualify if:

• Significant renal or hepatic impairment.
• Unstable ischemic heart disease, cardiac dysrhythmias, coronary/peripheral artery bypass graft or cerebrovascular accident within 6 months prior to starting treatment
• Uncontrolled arterial hypertension despite medical treatment.
• Ongoing congestive heart failure or cardiac dysrhythmias of NCI CTCAE Grade ≥2 or uncontrolled atrial fibrillation.
• On-going significant infection (chest, urine, blood, intra-abdominal).
• Uncontrolled diabetes.
• Scheduled elective surgery or other procedures requiring general anaesthesia during the trial.
• Patients who have undergone major surgery ≤ 4 weeks prior to starting study drug or who have not recovered from side effects of such procedure
• Previous targeted therapies to the pancreatic adenocarcinoma (including radiofrequency ablation or radiotherapy)
• History of other malignancy less than 3 years before the diagnosis of current cancer, EXCLUDING the following: Non-melanoma skin cancer, in situ carcinoma of the cervix treated surgically with curative intent, other malignant tumours that have been treated curatively and patient is deemed disease-free
• Endocrine therapy - patients with prostate cancer may continue to receive endocrine therapy to maintain castrate levels of androgens
• Known allergic reactions to any of the drugs or liposomal components or intravenous imaging agents used in this study
• Resting ECG with QTc \>480msec at 2 or more time points within a 24h period (using Fredericia correction).
• Other severe acute or chronic medical or psychiatric conditions or laboratory abnormalities that the investigator considers would make the patient a poor trial candidate, would impart excess risk associated with study participation or drug administration or could interfere with protocol compliance or the interpretation of trial results.
• Female participant who is pregnant, lactating or planning pregnancy during the course of the trial. However, those female patients who have a negative serum pregnancy test before enrolment and agree to use one highly effective form of contraception (oral, injected or implanted hormonal contraception or intrauterine device) in addition to condom plus spermicide, for four weeks before entering the trial, during the trial and for six months afterwards are considered eligible.

Sponsors & Collaborators

• University of Oxford: lead
• National Institute for Health Research, United Kingdom: collaborator
• Imunon: collaborator

Study Sites (1)

Oxford University Hospitals NHS Trust

Oxford, OX3 7LE, United Kingdom

Location

Related Publications (1)

• Spiers L, Gray M, Lyon P, Sivakumar S, Bekkali N, Scott S, Collins L, Carlisle R, Wu F, Middleton M, Coussios C. Clinical trial protocol for PanDox: a phase I study of targeted chemotherapy delivery to non-resectable primary pancreatic tumours using thermosensitive liposomal doxorubicin (ThermoDox(R)) and focused ultrasound. BMC Cancer. 2023 Sep 23;23(1):896. doi: 10.1186/s12885-023-11228-z.

  PMID: 37741968 DERIVED

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Doxorubicin

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Mark Middleton

  Consultant Medical Oncologist and Professor of Experimental Cancer Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: prospective non-randomised safety cohort study

Study Record Dates

• First Submitted: April 7, 2021
• First Posted: April 21, 2021
• Study Start: June 16, 2021
• Primary Completion: March 30, 2023
• Study Completion: March 30, 2023
• Last Updated: April 12, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)