Intraperitoneal bevacizumab for recurrent malignant ascites in chemotherapy resistant solid tumours: a randomised trial (REZOLV3R).
Efficacy of intraperitoneal bevacizumab for decreasing or delaying re-accumulation of recurrent malignant ascites in chemotherapy resistant solid tumours: a randomised trial (REZOLV3R)
The University of Sydney
100 participants
Dec 20, 2024
Interventional
Conditions
Summary
The purpose of this study is to investigate whether a short injection of a drug called bevacizumab into the abdominal cavity (known as intraperitoneal infusion) after drainage of excess fluid in the abdomen may delay the return of the ascites compared to an injection of saline only. Who is it for? You may be eligible for this study if you are an adult with symptomatic, cytologically confirmed malignant ascites arising from a solid organ malignancy, excluding pancreatic cancer. In addition, you are either not receiving or not planned to receive additional systemic anticancer treatment for the duration of study treatment. Study details Participants will be randomly allocated to either receive bevacizumab with saline, or saline alone, into the abdominal cavity through an intraperitoneal infusion. This will be followed by a larger infusion of saline over a 30-60 minute period. This therapeutic drainage process may be repeated for re-accumulation of ascites during the study period, if required. Data from participant electronic medical records and quality of life questionnaires will be collected. It is hoped that this research will help demonstrate the potential activity of bevacizumab to decrease or delay the re-accumulation of malignant ascites.
Eligibility
Inclusion Criteria11
- 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
- Age: 18 years and over
- Eastern Cooperative Oncology Group (ECOG) performance status 0-3
- Estimated survival of 12 weeks or more
- Study treatment both planned and able to start within 14 days of registration
- Willing and able to comply with all study requirements, including treatment timing and/or nature of required assessments
- Signed, written informed consent.
Exclusion Criteria16
- 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
- Active or non-healing intra-abdominal fistulae or history of fistulae within previous 60 days
- Major surgery within the preceding 6 weeks
- Pulmonary emboli or deep vein thrombosis unless on anticoagulation and no thrombotic episode in the preceding 6 weeks
- Known bleeding diathesis, or history of active bleeding including known gastric ulceration within 60 days
- Uncontrolled hypertension, or unstable cardiac disease
- Concurrent illness, including severe infection that may jeopardize the ability of the patient to undergo the procedures outlined in this protocol with reasonable safety
- Serious medical or psychiatric conditions that might limit the ability of the patient to comply with the protocol
- 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.
- Previous episode of ascites due to non-malignant causes, for example hepatic failure, portal venous obstruction
- Known hypersensitivity to or serious reaction resulting from any components of bevacizumab, Chinese hamster ovary cell products or other recombinant human or humanised antibodies
- Have received anti-VEGF therapy within the last 4 weeks.
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Interventions
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.
Locations(5)
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ACTRN12624000288527