Octreotide in Treating Patients With Cancer-Related Malignant Ascites

Study Overview
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Brief Summary
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RATIONALE: Octreotide may be an effective treatment for malignant ascites. It is not yet known whether octreotide is more effective than a placebo in treating malignant ascites. PURPOSE: This randomized phase III trial is studying octreotide to see how well it works compared to placebo in treating patients with cancer-related malignant ascites.

Detailed Description
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OBJECTIVES: Primary Compare the efficacy of octreotide vs placebo, in terms of extending the time-to-paracentesis, in patients with cancer-related symptomatic malignant ascites. Secondary Compare the number of paracenteses in patients treated with these drugs. Determine the toxicity of octreotide in these patients. Compare the quality of life of patients treated with these drugs. OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to anticipated ongoing chemotherapy (yes vs no), frequency of prior paracentesis (never vs other), and prior chemotherapy (never vs only first-line chemotherapy vs second-line chemotherapy vs other). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive octreotide subcutaneously (SC) once on day 1. Arm II: Patients receive placebo SC once on day 1. In both arms, treatment with intramuscular octreotide or placebo repeats monthly for up to 2 years in the absence of unacceptable toxicity. Quality of life is assessed at baseline, 2 weeks, and then monthly for up to 2 years during study treatment. After completion of study treatment, patients are followed every 6 months for up to 2 years.

Official Title
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An Exploratory, Randomized, Placebo-Controlled Trial of Depot Octreotide (Sandostatin LARDepot) for Symptomatic Ascites in Cancer Patients

Conditions
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Metastatic Cancer, Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Drug: octreotide acetate
* Other: placebo


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed cancer Diagnosis of malignant ascites, as determined by the treating oncologist Positive cytology not required Patient is symptomatic and views ascites as a problem No lymphoma or lymphomatous ascites Planning therapeutic paracentesis ≤ 3 days after study entry OR completed therapeutic paracentesis 2 days before study entry PATIENT CHARACTERISTICS: Age 18 and over Performance status Not specified Life expectancy At least 4 weeks Hematopoietic Not at high risk of bleeding from a procedure Hepatic No known cirrhosis or portal hypertension Renal No known history of chronic renal failure, defined as creatinine ≥ 2 times upper limit of normal Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Prior cholecystitis allowed provided patient underwent cholecystectomy No uncontrolled diabetes mellitus No known allergy to octreotide No known allergy to latex No medical condition that would preclude study treatment PRIOR CONCURRENT THERAPY: Biologic therapy No concurrent bevacizumab Chemotherapy No concurrent intraperitoneal chemotherapy No concurrent first-line chemotherapy for any cancer except pancreatic cancer Concurrent second-line chemotherapy or later-line chemotherapy allowed Endocrine therapy No other concurrent octreotide Radiotherapy Not specified Surgery Not specified Other No concurrent therapeutic warfarin Concurrent prophylactic warfarin at a dose of 1 mg/day allowed No other concurrent treatment for ascites except paracentesis or ongoing diuretics

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>Patients receive octreotide subcutaneously (SC) once on day 1. | Drug: octreotide acetate<br>* Given subcutaneously<br>|
| Placebo Comparator: Arm II<br>Patients receive placebo SC once on day 1. | Other: placebo<br>* Given subcutaneously<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Time to Paracentesis | Kaplan Meier curves will be constructed for each group; patients lost to follow up will be censored. A log rank test will be used to compare groups. We will adjust for the volume of fluid withdrawn at paracentesis and for change in abdominal circumference between baseline and the next procedure because a patient may require an extra paracentesis if only a small volume is withdrawn at baseline. | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Paracenteses | We will compare the number of paracenteses between groups. Parametric or nonparametric testing will be used as appropriate. | Up to 2 years | 
| Average Quality-of-life | Quality of life will be recorded and analyzed in a descriptive, exploratory fashion. We acknowledge that this study will represent the first to attempt a prospective assessment of quality of life in patients with symptomatic ascites. The underlying hypothesis of this quality of life assessment is that patients who are receiving octreotide will enjoy a better quality of life compared to patients who receive placebo. Quality of life scores from the CLDQ will be summed for all patients on a monthly basis. Again we anticipate high patient drop out rates over time within these two cohorts. With due diligence, we will attempt to ascertain the reason for each patient drop out, and appropriate imputation techniques will be employed for each.Quantified as: 1='All of the time' 2='Most of the time' 3='A good bit of the time' 4='Some of the time' 5='A little bit of the time' 6='Hardly any of the time' 7='None of the time' 0='Missing'; | Up to 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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unspecified adult solid tumor, protocol specific, malignant ascites