Evaluation of the Efficacy of Diuretics for Symptomatic Malignant Ascites Episodes in Advanced Stage of Cancer (DIASC)

Cancer Clinical Trial

Official title:

A Randomized Cross-over Trial Evaluating the Efficacy of Diuretics for Symptomatic Malignant Ascites Episodes in Advanced Palliative Stage of Cancer

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02501213
• Other study ID #: DIASC-1507
• Status: Terminated
• Phase: Phase 2
• Start date: May 30, 2016
• Est. completion date: December 24, 2018

Study information

• Verified date: May 2019
• Source: Centre Oscar Lambret
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

While some authors recommend diuretics as the first treatment to initiate for symptoms caused by malignant ascites (MA), their prescription is variable. No randomized, controlled study has assessed their benefit in this context. According to literature, diuretics may bring relief in about 40% of cases, regardless of primary tumor.

The purpose of our study is to assess the effectiveness of diuretic treatment according to Serum Ascites Albumin Gradient (SAAG) measured before treatment. Judgment criteria is the time elapsed between recurrent MA that requires paracentesis. The investigators will also examine whether SAAG and serum levels of renin and aldosterone can predict symptom response to diuretics.

Description:

Patients eligible for the trial and having signed their consent to participate will be randomized to arm A or B.

Treatment order is randomly attributed to patients at the 1st paracentesis, after the reception of the laboratory results necessary to evaluate SAAG value. Randomization is stratified 1:1 according to SAAG values (≥ or < to 11g/L) and Systemic treatment (yes or not)

• Patients randomized to arm A will be observed until the next episode requiring paracentesis (due to clinical symptoms : abdominal pain or heaviness, dyspnoea, orthopnoea, nausea/vomiting, anorexia, early satiety, gastro-oesophageal reflux, lower limb and genital oedema), at which time they will receive arm B (diuretics), in absence of contra-indication to diuretic treatment.

• Patients randomized to arm B will receive diuretics until the next episode requiring paracentesis, at which time they will receive arm A (observation).

Patients will have a physical assessment within 24 hours prior to the start of treatment, once every two weeks for patients randomized in arm A and each week for patients randomized in arm B, at cross-over and at the end of the study. Patient will also have a biological assessment within 24 hours prior to the start of treatment, twice a week for patients randomized in arm B, at cross-over and at the end of the study. Finally, they will address a quality of life questionnaire (QLQ-C15-PAL) prior to the start of treatment, at cross-over and at the end of the study.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 14
• Est. completion date: December 24, 2018
• Est. primary completion date: November 23, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients with advanced stage cancer

• First episode of malignant ascites

• Grade 2 or 3 ascites

• Clinically symptomatic ascites requiring paracentesis due to : abdominal pain or heaviness, dyspnoea, orthopnoea, nausea/vomiting, anorexia, early satiety, gastro-oesophageal reflux, lower limb and genital oedema

• Age = 18 years

• Performance status = 3

• Life expectancy = 1 month

• Absence of contra-indication to diuretic treatment

• Patient regularly followed up by a palliative care or supportive care team

• Signed and dated informed consent

Exclusion Criteria:

• Hepatic disorders : cirrhosis, hepatitis, hepatocellular insufficiency, hepatic encephalopathy

• Non malignant ascites

• Hydroelectrolytic disorders: hyponatremia (< 130 mmol/L) or hyperkaliemia (> 5 mmol/L) or severe hypokaliemia (< 3 mmol/L)

• Functional acute renal insufficiency

• Urinary disorders : Obstruction in the urinary tract, Oliguria/anuria

• Chronic renal failure

• Patient unable to swallow

• Sulfamides allergy

• Hypersensitivity to spironolactone or to any of the excipients

• Hypersensitivity to furosemide or to any of the excipients

• Pregnant or breastfeeding women

• Patient under guardianship

Related Conditions & MeSH terms

• Ascites
• Cancer

Intervention

Drug:
• Spironolactone (+/- Furosemide)
Administration of spironolactone alone 100 mg/day each morning, increased in increments of 100 mg / week to a maximum of 400 mg / day in the absence of efficiency. In case of ineffectiveness or hyperkalemia: addition of Furosemide 40 mg / day increased in increments of 40 mg / week to a maximum of 160 mg / day in the absence of efficiency.

Locations

Country	Name	City	State
France	Centre Hospitalier Intercommunal Compiègne-Noyon	Compiègne
France	Polyclinique de Grande Synthe	Grande Synthe
France	Centre Oscar Lambret	Lille
France	CHRU Lille	Lille
France	Hôpital Saint Vincent de Paul	Lille
France	GH Diaconesses Croix St Simon	Paris
France	Hôpital Jean Jaurès	Paris
France	Institut Curie	Paris
France	Hôpital Lyon Sud	Pierre-Bénite
France	Institut Jean Godinot	Reims
France	Centre Eugène Marquis	Rennes
France	Centre Paul Strauss	Strasbourg
France	Centre Hospitalier Tourcoing	Tourcoing
France	Polyclinique Vauban	Valenciennes
France	Institut Gustave Roussy	Villejuif

Sponsors (2)

Lead Sponsor	Collaborator
Centre Oscar Lambret	National Cancer Institute, France

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time between symptomatic malignant ascites episodes requiring paracentesis		Patients will be followed until their third malignant ascites episode, an expected average of 30 days.
Secondary	Tolerance	Adverse events and serious adverse events related to diuretic treatment according to NCI-CTCAE v4.0	Up to 30 days after the last administration of the product
Secondary	Quality of life based on the EORTC (European Organization for Research and Treatment of Cancer) QLQ-C15-PAL		At baseline (prior to the start of treatment)
Secondary	Quality of life based on the EORTC (European Organization for Research and Treatment of Cancer) QLQ-C15-PAL		At cross-over (approximately 15 days after inclusion)
Secondary	Quality of life based on the EORTC (European Organization for Research and Treatment of Cancer) QLQ-C15-PAL		At the end of the study (up to 6 months).
Secondary	Description of the patterns of prescription of diuretics	Growth pattern doses of diuretics, decrement pattern doses of diuretics, maintenance doses of diuretics, maximum doses reached of diuretics.	During randomization in arm B (that is to say during approximately 15 days between the first and the second or between the second and the third milgnant ascites episode).
Secondary	Predictive factors of response to diuretics : Serum Ascites Albumin Gradient (SAAG)		Within 24 hours prior to the start of treatment
Secondary	Predictive factors of response to diuretics : renin aldosterone plasmatic level		Within 24 hours prior to the start of treatment
Secondary	Predictive factors of response to diuretics : SAAG		Twice a week for patients randomized in arm B
Secondary	Predictive factors of response to diuretics : renin aldosterone plasmatic level		Twice a week for patients randomized in arm B
Secondary	Predictive factors of response to diuretics : SAAG		At cross-over (approximately 15 days after inclusion)
Secondary	Predictive factors of response to diuretics : renin aldosterone plasmatic level		At cross-over (approximately 15 days after inclusion)
Secondary	Predictive factors of response to diuretics : SAAG		At the end of the study (up to 6 months).
Secondary	Predictive factors of response to diuretics : renin aldosterone plasmatic level		At the end of the study (up to 6 months).