Intraperitoneal bevacizumab for recurrent malignant ascites in chemotherapy resistant solid tumours: a randomised trial (REZOLV3R).

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.