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Trial registered on ANZCTR


Registration number
ACTRN12624000288527
Ethics application status
Approved
Date submitted
13/11/2023
Date registered
20/03/2024
Date last updated
29/09/2024
Date data sharing statement initially provided
20/03/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Intraperitoneal bevacizumab for recurrent malignant ascites in chemotherapy resistant solid tumours: a randomised trial (REZOLV3R).
Scientific title
Efficacy of intraperitoneal bevacizumab for decreasing or delaying re-accumulation of recurrent malignant ascites in chemotherapy resistant solid tumours: a randomised trial (REZOLV3R)
Secondary ID [1] 310952 0
CTC 0398
Universal Trial Number (UTN)
Trial acronym
REZOLV3R
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Recurrent malignant ascites 332030 0
Chemotherapy resistant solid tumours 332031 0
Condition category
Condition code
Cancer 328759 328759 0 0
Any cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
All participants will receive therapeutic paracentesis according to local guidelines, followed over 30 minutes by 100mL normal saline plus either 400mg MVASI® (bevacizumab group) or 100mL normal saline alone (control group), via the same intraperitoneal catheter/drain.
For participants in both groups, this is followed over an additional 30 minutes by a further 400mL normal saline via the same intraperitoneal catheter/drain, to facilitate distribution throughout the peritoneal cavity.
Temporary catheters should then be removed following usual procedure, without draining the bevacizumab/saline. Permanent indwelling intraperitoneal catheters can be left in-situ but should not be accessed for intermittent drainage until the primary endpoint has occurred (recurrent, symptomatic ascites).
Participants requiring subsequent paracenteses may be treated with intraperitoneal bevacizumab, provided by the study, at the discretion of the participant and clinician.
Bevacizumab or control should be prepared by a healthcare professional using aseptic technique. Withdraw the necessary amount of bevacizumab and dilute to the required administration volume with 0.9% sodium chloride solution. The concentration of the final bevacizumab solution should be kept within the range of 1.4-16.5 mg/mL.
If the patient has re-accumulation of ascites that requires a paracentesis for symptom relief, then a second dose of bevacizumab may be administered at repeat drainage (referred to as second on-study drainage).
From the second drainage onwards, intraperitoneal bevacizumab may be given irrespective of treatment group.
There may be a small group of patients who have a significant benefit and a delay in the re-accumulation of ascites of around 42 days after the second intraperitoneal administration of bevacizumab and who may potentially have a third dose or more, providing there are no contraindications to further therapy (see criteria for ineligibility). These patients will all be assessed on a case-by-case basis and will involve discussion between the TMC and investigator to ensure that there are no contraindications to repeat administration.
Intervention code [1] 327379 0
Treatment: Drugs
Comparator / control treatment
Therapeutic drainage of malignant ascites per local institutional protocol by intraperitoneal administration of 100mL saline. This is followed by a further 400mL saline over a total of 30-60 minutes via the same intraperitoneal catheter/drain. This may be repeated if another therapeutic drainage is required.
Control group
Placebo

Outcomes
Primary outcome [1] 336563 0
To compare between each treatment group (bevacizumab or control):
Post-treatment Paracentesis Free Survival Time (PFST) (First paracentesis on trial (P0) to the earliest of next paracentesis (P1) or death)
Timepoint [1] 336563 0
First paracentesis on trial (P0) to the earliest of next paracentesis (P1) or death.
Secondary outcome [1] 428821 0
To evaluate changes in quality of life from patient-reported outcomes (PRO) in each treatment group using 3 patient questionnaires. These will be assessed as a composite outcome.
Timepoint [1] 428821 0
PRO will be collected at baseline, 4 week follow up until death and at each subsequent ascitic drainage. ICECAP-SCM questions are administered at baseline and at 1st follow-up visit only.
Secondary outcome [2] 432474 0
To determine the subsequent paracentesis ratio between each treatment group.
Timepoint [2] 432474 0
Post-treatment Paracentesis Free Survival Time (PFST) as collected from electronic medical records. Numbers of subsequent paracentesis will be collected at each follow up visit. and any subsequent paracentesis.
Secondary outcome [3] 432475 0
To determine number of subsequent paracenteses between each treatment group.
Timepoint [3] 432475 0
Numbers of subsequent paracentesis will be collected at each follow up visit. and any subsequent paracentesis.
Secondary outcome [4] 432476 0
To assess intervals between subsequent paracentesis in each treatment group.
Timepoint [4] 432476 0
The interval measured in days, will be collected at each follow up visit. and any subsequent paracentesis.
Secondary outcome [5] 432477 0
Overall survival (OS) will be examined between each treatment group
Timepoint [5] 432477 0
This will be collected from electronic medical records at the date of last known follow-up alive.
Secondary outcome [6] 432478 0
Healthcare resource use and health system costs will be examined between the two treatment groups.
Timepoint [6] 432478 0
This will be determined at the end of the trial.
Secondary outcome [7] 432484 0
Incremental healthcare costs, outcomes, and cost-effectiveness ratios will be examined between the two treatment groups.
Timepoint [7] 432484 0
This will be determined at the end of the trial.

Eligibility
Key inclusion criteria
1. Patients with symptomatic, cytologically confirmed malignant ascites:
a. who have any solid organ malignancy excluding pancreatic cancer
b. who are either not receiving or not planned to receive additional systemic anticancer treatment for the duration of study treatment
c. that has recurred following at least one therapeutic ascitic drainage within 28 days prior to study registration
d. who require therapeutic paracentesis for symptomatic management
2. Age: 18 years and over
3. Eastern Cooperative Oncology Group (ECOG) performance status 0-3
4. Estimated survival of 12 weeks or more
5. Study treatment both planned and able to start within 14 days of registration
6. Willing and able to comply with all study requirements, including treatment timing and/or nature of required assessments
7. Signed, written informed consent.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. At high risk of bowel perforation, including but not limited to any one or more of the following:
a. History of bowel obstruction within 6 months prior to study entry
b. CT scan that demonstrates involvement of bowel by tumour
c. Symptoms to suggest impending bowel obstruction
d. Prior whole abdominal radiotherapy
2. Active or non-healing intra-abdominal fistulae or history of fistulae within previous 60 days
3. Major surgery within the preceding 6 weeks
4. Pulmonary emboli or deep vein thrombosis unless on anticoagulation and no thrombotic episode in the preceding 6 weeks
5. Known bleeding diathesis, or history of active bleeding including known gastric ulceration within 60 days
6. Uncontrolled hypertension, or unstable cardiac disease
7. Concurrent illness, including severe infection that may jeopardize the ability of the patient to undergo the procedures outlined in this protocol with reasonable safety
8. Serious medical or psychiatric conditions that might limit the ability of the patient to comply with the protocol
9. Pregnancy, lactation, or inadequate contraception. Women must be post-menopausal, infertile, or use a reliable means of contraception. Women of childbearing potential must have a negative pregnancy test done within 7 days prior to registration.
10. Previous episode of ascites due to non-malignant causes, for example hepatic failure, portal venous obstruction
11. Known hypersensitivity to or serious reaction resulting from any components of bevacizumab, Chinese hamster ovary cell products or other recombinant human or humanised antibodies
12. Have received anti-VEGF therapy within the last 4 weeks.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Enrolment and Randomisation will be performed online via the study’s clinical data system, REDCap.
Sites will only be able to randomise a participant after all required approvals are in place for study activation, including data system access.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Within this study, randomisation via permutated blocks will be utilised. The method of generating the allocation sequence is computer generated random numbers. The randomisation will be stratified by primary tumour site (gynaecological vs non-gynaecological malignancy), ECOG performance status (0-1 vs 2-3), prior intravenous bevacizumab (yes vs no), clinical study site, and catheter type (temporary vs indwelling).
Once the randomisation process has been completed, the participant will be assigned to a treatment group by REDCap, and confirmation of randomisation including study number and allocation will be provided to the site.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
5/08/2024
Actual
Date of last participant enrolment
Anticipated
31/12/2028
Actual
Date of last data collection
Anticipated
31/12/2029
Actual
Sample size
Target
200
Accrual to date
0
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 26869 0
Concord Repatriation Hospital - Concord
Recruitment hospital [2] 26870 0
Mater Sydney - North Sydney
Recruitment postcode(s) [1] 42932 0
2139 - Concord
Recruitment postcode(s) [2] 42933 0
2060 - North Sydney

Funding & Sponsors
Funding source category [1] 315209 0
Government body
Name [1] 315209 0
Cancer Australia
Country [1] 315209 0
Australia
Primary sponsor type
University
Name
The University of Sydney
Address
Level 3, Michael Spence Building (F23), Corner of Eastern Avenue and City Road, The University of Sydney NSW 2006
Country
Australia
Secondary sponsor category [1] 317242 0
None
Name [1] 317242 0
Address [1] 317242 0
Country [1] 317242 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 314134 0
Sydney Local Health District HREC – Concord Repatriation General Hospital
Ethics committee address [1] 314134 0
Ethics committee country [1] 314134 0
Australia
Date submitted for ethics approval [1] 314134 0
26/02/2024
Approval date [1] 314134 0
28/02/2024
Ethics approval number [1] 314134 0
CH62/6/2023-176

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 130534 0
Dr Katrin Marie Sjoquist
Address 130534 0
NHMRC Clinical Trials Centre University of Sydney, Levels 4-6 Medical Foundation Building, 92-94 Parramatta Rd, Camperdown NSW 2050
Country 130534 0
Australia
Phone 130534 0
+61416013904
Fax 130534 0
Email 130534 0
katrin.sjoquist@sydney.edu.au
Contact person for public queries
Name 130535 0
Sibyl Masterman
Address 130535 0
NHMRC Clinical Trials Centre University of Sydney, Levels 4-6 Medical Foundation Building, 92-94 Parramatta Rd, Camperdown NSW 2050
Country 130535 0
Australia
Phone 130535 0
+61 280365272
Fax 130535 0
Email 130535 0
rezolv3r.study@sydney.edu.au
Contact person for scientific queries
Name 130536 0
Sybil Masterman
Address 130536 0
NHMRC Clinical Trials Centre University of Sydney, Levels 4-6 Medical Foundation Building, 92-94 Parramatta Rd, Camperdown NSW 2050
Country 130536 0
Australia
Phone 130536 0
+61 280365272
Fax 130536 0
Email 130536 0
rezolv3r.study@sydney.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Currently no plan and participant informed consent will be required.


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
No additional documents have been identified.