Malignant Ascites Alfapump® Study

Study Overview
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Brief Summary
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ProMAS is a prospective post-marketing, single-arm study to assess performance and safety of the Alfapump® system in the treatment of patients with malignant ascites. The study aims to enroll 40 patients in up to 8 sites in Europe.

Detailed Description
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The Prospective Malignant Ascites Alfapump® study is a single-arm, prospective study to evaluate the performance and safety of the Alfapump® system in the treatment of patients with malignant ascites. The Alfapump® system is a fully implantable programmable pump, able to move ascitic fluid from the peritoneal cavity to the bladder via 2 catheters. The Alfapump® has obtained CE (Conformité Européenne) mark approval for the indication of malignant ascites. The primary objective of the study is to assess the performance of the system to remove ascites. Secondary objectives are to evaluate the safety and tolerability of the Alfapump® in the treatment of malignant ascites for a total follow-up period of 9 months, and to evaluate quality of life (QoL) by reduction or elimination of paracentesis requirement. Furthermore the study includes an exploratory scientific objective as to feasibility to obtain 'liquid biopsy' samples suitable for analysis in a non-invasive way after Alfapump® implantation. 40 patients with malignant ascites will be enrolled in up to 8 sites in Europe (Belgium, United Kingdom, Switzerland). Specific sub-analysis of data from patients with gynecological (ovarian) cancer is planned.

Official Title
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Prospective Study in the Use of the Alfapump® in the Treatment of Malignant Ascites

Conditions
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Malignant Ascites

Intervention / Treatment
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* Device: alfapump system


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is ≥ 18 years of age; Subject has provided written informed consent; 3.Subject has recurrent malignant ascites defined as ≥2 therapeutic paracenteses in the month prior to enrolment; 4.Subject has sufficient baseline data documented for at least 4 paracentesis events in the last 3 months pre-implant, including date and volume; 5.Subject has ascites following neoplastic disease, as assessed by physician. In subjects with primary malignancy of the liver it should be confirmed that the ascites is due to malignancy and not due to underlying pre-existing cirrhosis. 6.Subject has a life expectancy of ≥3 months as assessed by the treating physician, and is receiving or intended to receive anticancer therapy. 7.Subject has the ability to comply with study procedures, including all follow-up visits at implanting centre when required, and ability to perform subject-required system tasks (charging). A subject with a caregiver who can comply with the study procedures and to perform the tasks required for appropriate pump function is allowed as well. Exclusion Criteria: Subject has evidence of multiple ascites loculation Ascites analysis with neutrophil count >250/µl within 24-hours prior to implant. Subject has acute Urinary Tract Infection (UTI) within 24-hours of implantation assessed by urinalysis. Subject has skin infection of the abdominal wall at the area of implantation. Subject has a serum creatinine > 1.5 mg/dL Subject has Subject has obstructive uropathy (bladder residual volume >100 mL, determined by catheterization or abdominal ultrasound) in case of Lower Urinary Tract Symptoms (LUTS) . Existing bladder anomaly denying proper catheterization of the bladder. Subject has active bleeding or thrombocytopenia < 45,000 X106/L. Subject on long-term prophylactic anticoagulation Subject is pregnant or a female of childbearing potential. Patient has recurrent requirement for MRI Subject is currently participating in an oncology trial which might be negatively affected by the alfapump as assessed by the treating physician

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Device: alfapump system|active implantable device for treatment of malignant ascites|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Monthly therapeutic paracentesis frequency up to 3 months | Monthly therapeutic paracentesis frequency up to 3 months compared to the baseline therapeutic paracentesis frequency. The monthly therapeutic paracentesis frequency up to 3 months is defined as the average rate of therapeutic paracenteses during month 1, 2 and 3 post-implantation. Baseline therapeutic paracentesis frequency is defined as the average rate of therapeutic paracentesis in the 3 months prior to pump implantation. | 3 months post-implantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Monthly therapeutic paracentesis frequency up to 6 months | Monthly therapeutic paracentesis frequency up to 6 months compared to the baseline therapeutic paracentesis frequency. The monthly therapeutic paracentesis frequency at 6 months is defined as the average rate of therapeutic paracenteses during months 1 to 6 Baseline therapeutic paracentesis frequency is defined as the average rate of therapeutic paracentesis in the 3 months prior to pump implantation. | 6 months post-implantation | 
| Safety outcome: free survival | Therapeutic paracentesis free survival after Alfapump® implantation | Time (days) to first paracentesis after implantation through 270 days post implantation | 
| Efficacy outcome- Assessment of changes in Quality of Life | Changes in Quality of life after Alfapump® implantation, measured with validated EORTC cancer related Quality of life Questionnaire-CR29 (ColoRectal 29 questions) in subjects with colorectal malignancy. | at 1-month, 3-month, 6-month and 9-month follow-up compared to baseline | 
| Efficacy outcome- Assessment of changes in Quality of Life | Changes in Quality of life after Alfapump® implantation assessed with validated FACIT-AI 5Ascites Index) ascites related quality of life questionnaire in all subjects enrolled in the study. | at 1-month, 3-month, 6-month and 9-month follow-up compared to baseline | 
| Efficacy outcome- Assessment of changes in Quality of Life | Changes in Quality of life after Alfapump® implantation, measured with validated EORTC-cancer related Quality of life questionnaire-OV28 (OVarian 28 questions), in subjects with a gynaecological malignancy. | at 1-month, 3-month, 6-month and 9-month follow-up compared to baseline | 
| Nutritional status outcome | Change in nutritional status assessed by Psoas muscle measurement | at 1-month, 3-month, 6-month and 9-month follow-up compared to baseline | 
| Nutritional status outcome | Change in nutritional status assessed by changes in serum Zinc | at 1-month, 3-month, 6-month and 9-month follow-up compared to baseline | 
| Nutritional status outcome | Change in nutritional status assessed by changes in serum pre-albumin | at 1-month, 3-month, 6-month and 9-month follow-up compared to baseline | 
| Nutritional status outcome | Change in nutritional status assessed by changes in serum phosphate | at 1-month, 3-month, 6-month and 9-month follow-up compared to baseline | 
| Nutritional status outcome | Change in nutritional status assessed by changes in serum potassium | at 1-month, 3-month, 6-month and 9-month follow-up compared to baseline | 
| Nutritional status outcome | Change in nutritional status assessed by changes in serum albumin | at 1-month, 3-month, 6-month and 9-month follow-up compared to baseline | 
| Pump performance | Total Monthly volume of ascitic fluid removed (sum of volumes removed during each month via either Alfapump® and via therapeutic paracentesis) | at 1-month, 3-month, 6-month and 9-month follow-up | 
| Pump performance outcome - pump survival | Pump survival through study completion, up to 270 days post-pump implantation | Time (days) from implantation until explantation due to technical causes through study completion up to 270 days post-pump implantation | 
| Pump performance outcome - pump survival | Pump survival through study completion, up to 270 days post-implantation | Time (days) from implantation until first exchange due to technical causes through study completion up to 270 days post-pump implantation | 
| Pump performance outcome | Frequency of hospitalisations following Alfapump® implantation through study completion up to 270 days post-pump implantation | through study completion up to 270 days post-pump implantation | 
| Pump performance outcome | Duration of hospitalisations following Alfapump® implantation through study completion up to 270 days post-pump implantation | throug study completion up to to 270 days post-pump implantation | 
| Safety outcome - subject survival | Subject overall survival after Alfapump® implantation through study completion up to 270 days post-pump implantation | Time (days) until exitus through study completion up to 270 days post-pump implantation | 
| Safety outcome- Bladder metastasis: Freedom from metastatic bladder wall infiltration | Freedom from metastatic bladder wall infiltration as assessed by cystoscopy | at 6-month follow-up | 
| Safety outcome- Worsening of renal function | Incidence of subjects suffering Renal function deterioration, defined as a rise in serum creatinine of ≥50% or ≥0.3mg/dl . | at 3-month, 6-month and 9-month follow-up compared to baseline | 
| Safety outcome- Incidence of device related infection | Incidence of Device-related infections following pump-implantation | at 3-month, 6-month and 9-month follow-up | 
| Safety outcome- Incidence of Procedure related events | Incidence of Procedure related adverse events | At 1 month follow-up. | 
| Safety outcome- Incidence of Device related events | Incidence of any Device-related adverse events | at 3-month, 6-month and 9-month follow-up | 
| Device failure | Incidence of device failure resulting in re-intervention (Revision, exchange or explantation) through study completion up to 270 days post-pump implantation | Through study completion up to 270 days post-pump implantation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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OVARIAN, COLORECTAL, PARACENTESIS