Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12620001216909
Ethics application status
Approved
Date submitted
8/09/2020
Date registered
16/11/2020
Date last updated
28/07/2023
Date data sharing statement initially provided
16/11/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Curcumin as a palliative treatment for malignant pleural effusion
Scientific title
A phase 1 study establishing the safety of intrapleural administration of liposomal curcumin (LipoCurc) as a palliative treatment for malignant pleural effusion
Secondary ID [1] 302206 0
None
Universal Trial Number (UTN)
Trial acronym
IPAL-MPE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Malignant pleural effusion 318896 0
Condition category
Condition code
Cancer 316880 316880 0 0
Any cancer
Respiratory 317331 317331 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
A single dose of liposomal curcumin, with the amount adjusted based on body mass (milligrams per metre squared (mg/m2)), will be administered to each participant by a respiratory clinician into their pleural cavity via an existing TIPC. Administration of the test drug will take approximately 15 minutes. Participants will not be randomised. Participants will receive ascending doses with each new cohort being administered the next dose. An initial cohort will be administered 100 mg/m2, a subsequent group will receive a single dose of 200 mg/m2 of liposomal curcumin and a final group will be administered a single dose of 300 mg/m2 of liposomal curcumin.
Intervention code [1] 318497 0
Treatment: Drugs
Comparator / control treatment
Uncontrolled
Control group
Uncontrolled

Outcomes
Primary outcome [1] 325049 0
Determine if the maximum tolerated dose (MTD) of liposomal curcumin can be reached as determined by the identification of dose limiting toxicities (DLTs) within the pre-determined escalating dose range. DLTs will be assessed using The National Cancer Institute Common Terminology Criteria for Adverse Events version 5 (NCI-CTCAE v5.0), guidelines.
Timepoint [1] 325049 0
Primary outcome 1 (MTD) will be assessed for up to one week post administration of the single dose of the trial intervention.
Primary outcome [2] 325050 0
Determine the feasibility of intrapleural administration of liposomal curcumin via an existing TIPC as indicated by results obtained from radiographic imaging (x-ray and computed tomogram), blood tests, monitoring of vital signs (heart rate, oxygen saturation and blood pressure), and where possible analysis of drained pleural fluid. Heart rate and oxygen saturation will be monitored using a finger pulse monitor with oximeter. Blood pressure will be monitored using a sphygmomanometer.
Timepoint [2] 325050 0
Primary outcome 2 feasibility assessment methods will be undertaken throughout study participation for up to 25 weeks in total with varying schedules. Assessment of vital signs will occur pre-intervention (baseline) week -1, then post-intervention every 15 minutes during first hour, then every hour for 4 hours, then at 4 hourly intervals up to 48 hours (week 0). Then at weeks 1, 4, 8, 12 and 24 post intervention. Blood samples will be obtained in weeks -1, 0 (pre-administration, and 2, 24 and 48 hours post administration), and at weeks 1, 4, 8, 12 and 24. A chest x-ray will be taken in weeks -1, 0 (at 48 hours post administration), 1, 4, 8, 12 and 24. A chest computed tomogram will be taken at weeks -1 and 8. Pleural fluid samples will be obtained in weeks -1 and 0, and when possible until end of trial participation.
Secondary outcome [1] 386669 0
Determine the effects of the study intervention on quality of life based on the average scores as assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ).
Timepoint [1] 386669 0
Secondary outcomes on quality of life will be assessed for up to 25 weeks as follows: -1 week pre-intervention (baseline), then, 2, 24 and 48 hours post intervention, then at weeks 1, 4, 8, 12 and 24 post intervention.
Secondary outcome [2] 386670 0
Determine the effects of the study intervention on feeling of breathlessness, based on the average scores as assessed by the Visual Analogue Scale for Breathlessness survey (VASB survey).
Timepoint [2] 386670 0
Secondary outcomes on feelings of breathlessness will be assessed for up to 25 weeks as follows: -1 week pre-intervention (baseline), then, 2, 24 and 48 hours post intervention, then at weeks 1, 4, 8, 12 and 24 post intervention.
Secondary outcome [3] 386671 0
Evaluation of safety and tolerability: Determine the rates of toxicities based on the National Cancer Institute Common Terminology Criteria for Adverse Events v5.0 (NCI CTCAE v5.0).
Timepoint [3] 386671 0
Secondary outcomes on rates of toxicities will be assessed for up to 25 weeks.
Secondary outcome [4] 386672 0
Evaluation of pharmacokinetics of curcumin in all participants following administration of a single dose of liposomal curcumin in to the intrapleural cavity from plasma and pleural fluid. The plasma concentration (C) of curcumin and its metabolite, tetrahydrocurcumin will be measured at various times points post-intervention. The following pharmacokinetic parameters will be examined; maximum plasma concentration (Cmax), time at which the maximum plasma concentration was reached (Tmax), time at which there is no detectable (below the lower limit of quantification) curcumin and tetrahydrocurcumin in the plasma and area under the plasma concentration-time curve (AUC). If a pleural effusion accumulates after the intervention individual patients we will measure pleural fluid concentration (C) of curcumin and tetrahydrocurcumin. The following pharmacokinetic parameters will be examined; maximum pleural fluid concentration (Cmax), time at which the maximum pleural fluid concentration was reached (Tmax), time at which there is no detectable (below the lower limit of quantification) curcumin and tetrahydrocurcumin in the pleural fluid.

Timepoint [4] 386672 0
Secondary outcomes will be assessed for up to 25 weeks as follows: -1 week pre-intervention (baseline), then week 0 pre-intervention, and at 2, 24 and 48hours post-intervention. Then at weeks 1, 4, 8, 12 and 24 post intervention.
Secondary outcome [5] 386673 0
Preliminary evaluation of any evidence of anti-tumour activity response. This will be assessed by responses to quality of life (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire) and feelings of breathlessness (Visual Analogue Scale for Breathlessness survey). And also comparative analyses of radiographic imaging assessed by chest X-ray and chest CT to evaluate and changes in the chest cavity; including changes in the size of the pleural effusion and the invading malignancy where possible. Pleural effusion cytology specimens will be assessed for changes to cancer cell histopathology from routine testing, where possible.
Timepoint [5] 386673 0
Secondary outcomes will be assessed throughout trial participation for up to 25 weeks.

Eligibility
Key inclusion criteria
1. Adults aged 18 years or older with an existing diagnosis of malignant pleural effusion on pleural biopsy or pleural fluid cytology in line with established standard practice for the diagnosis of malignant pleural effusion.
2. Individuals who have failed to respond to approved systemic therapies (chemotherapy, immune therapy or molecular targeted therapies), or who have progressive cancers following initial response to these therapies, and for whom no anti-tumour therapy of proven benefit is available at study enrolment.
3. People who have declined systemic therapies or are deemed not suitable for systemic therapies after consultation with a medical oncologist.
4. Recurrent symptomatic pleural effusion where insertion of a TIPC is clinically indicated.
5. Eastern Co-operative Performance Status 0 - 2.
6. Able to give signed informed consent.
4. People whose primary language is English.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Women who are pregnant and/or breastfeeding, and/or of childbearing age not taking contraceptive measures to avoid pregnancy while participating in the study.
2. People under 18 years of age.
3. People with mental impairment, or an unstable medical condition other than cancer, that may interfere with their ability to provide informed consent or ability to cooperate and participate in the study.
4. People with evidence of active hepatitis.
5. People with a diagnosis of lymphoma or a haematological cancer.
6. People with a history of haemolytic anaemia.
7. People with unresolved toxicities from prior systemic anti-cancer therapy.
8. People with an unstable cardiac condition as determined by the study investigator.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
28/08/2023
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
9
Accrual to date
0
Final
Recruitment in Australia
Recruitment state(s)
SA

Funding & Sponsors
Funding source category [1] 306626 0
Charities/Societies/Foundations
Name [1] 306626 0
Doug Henderson AO Research Fund Bequest
Country [1] 306626 0
Australia
Funding source category [2] 306678 0
Charities/Societies/Foundations
Name [2] 306678 0
Tour de Cure Pioneering Research Grant
Country [2] 306678 0
Australia
Primary sponsor type
University
Name
Flinders University
Address
Sturt Rd, Bedford Park, SA, 5042
Country
Australia
Secondary sponsor category [1] 307156 0
None
Name [1] 307156 0
n/a
Address [1] 307156 0
n/a
Country [1] 307156 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 306811 0
Southern Adelaide Local Health Network HREC
Ethics committee address [1] 306811 0
Flinders Medical Centre, Flinders Drive, Bedford Park, SA 5042
Ethics committee country [1] 306811 0
Australia
Date submitted for ethics approval [1] 306811 0
Approval date [1] 306811 0
25/05/2020
Ethics approval number [1] 306811 0

Summary
Brief summary
This study is investigating whether it is safe to administer curcumin packaged into small biological spheres called liposomes, to patients with malignant pleural effusion via a long-term chest drain directly into their pleural (lung) cavity.

Who is it for?
You may be eligible for this study if you are aged 18 years or older with an existing diagnosis of malignant pleural effusion, and you have failed to respond to approved systemic therapies (chemotherapy, immune therapy or molecular targeted therapies), or you have progressive cancers following initial response to these therapies.

Study details
The first three participants enrolled in this study will be administered 100 milligrams of curcumin per metre squared of body surface area, delivered directly into the tumour site via a pre-existing long-term chest drain, once only. If these participants do not present with any adverse effects, a second group of participants will be administered 200 milligrams of curcumin per metre squared of body surface area via their long-term chest drain. If the second group show no adverse effects a third, and final, group of participants will be administered 300 milligrams of curcumin per metre squared of body surface area. If the third group show no adverse effects, the maximum tolerated dose will not be reached within this pre-determined dose range, and the study will stop. All participants regardless of the maximum dose received will be asked to provide blood and tissue samples at ten different timepoints over the 25 weeks of the study. Additionally all participant will be asked to attend a total of 5 follow visits over the 25 weeks of the study.

It is hoped this research will determine whether curcumin given directly into the tumour site is safe, and whether it has any therapeutic effect on the cancer in the pleural cavity that is causing an MPE.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 105094 0
Dr Brendan Dougherty
Address 105094 0
Respiratory and Sleep Services, Flinders Medical Centre, Flinders Drive, Bedford Park, SA 5042
Country 105094 0
Australia
Phone 105094 0
+61 8 82045511
Fax 105094 0
Email 105094 0
[email protected]
Contact person for public queries
Name 105095 0
A/Prof Sonja Klebe
Address 105095 0
Anatomical Pathology, College of Medicine and Public Health, Flinders University, Flinders Medical Centre, Flinders Drive, Bedford Park, SA 5042
Country 105095 0
Australia
Phone 105095 0
+61 8 8204 3936
Fax 105095 0
Email 105095 0
[email protected]
Contact person for scientific queries
Name 105096 0
A/Prof Sonja Klebe
Address 105096 0
Anatomical Pathology, College of Medicine and Public Health, Flinders University, Flinders Medical Centre, Flinders Drive, Bedford Park, SA 5042
Country 105096 0
Australia
Phone 105096 0
+61 8 8204 3936
Fax 105096 0
Email 105096 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseStudy protocol of a phase 1 clinical trial establishing the safety of intrapleural administration of liposomal curcumin: Curcumin as a palliative treatment for malignant pleural effusion (IPAL-MPE).2021https://dx.doi.org/10.1136/bmjopen-2020-047075
N.B. These documents automatically identified may not have been verified by the study sponsor.