Metastatic Cancer, Unspecified Adult Solid Tumor, Protocol Specific
Conditions
Keywords
unspecified adult solid tumor, protocol specific, malignant ascites
Brief summary
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
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.
Interventions
DRUGoctreotide acetate
Given subcutaneously
OTHERplacebo
Given subcutaneously
Sponsors
National Cancer Institute (NCI)
Alliance for Clinical Trials in Oncology
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Median Time to Paracentesis | Up to 2 years | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Paracenteses | Up to 2 years | We will compare the number of paracenteses between groups. Parametric or nonparametric testing will be used as appropriate. |
| Average Quality-of-life | Up to 2 years | 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'; |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm I Patients receive 30 mg octreotide subcutaneously (SC) intramuscularly once on day 1. octreotide acetate: Given subcutaneously | 16 |
| Arm II Patients receive 2 milliliters placebo (0.9% sodium chloride) SC once on day 1. placebo: Given subcutaneously | 17 |
| Total | 33 |
Baseline characteristics
| Characteristic | Arm I | Arm II | Total |
|---|---|---|---|
| Age, Continuous | 62 years | 69 years | 63 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants | 17 Participants | 31 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Female | 10 Participants | 12 Participants | 22 Participants |
| Sex: Female, Male Male | 6 Participants | 5 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 16 / 16 | 16 / 17 |
| serious Total, serious adverse events | 1 / 16 | 0 / 17 |
Outcome results
Primary
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.
Time frame: Up to 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm I | Median Time to Paracentesis | 28 days |
| Arm II | Median Time to Paracentesis | 14 days |
p-value: 0.17Log Rank
Secondary
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';
Time frame: Up to 2 years
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Arm I | Average Quality-of-life | abdominal bloating | 4 QOL score |
| Arm I | Average Quality-of-life | shortness of breath | 4 QOL score |
| Arm I | Average Quality-of-life | abdominal discomfort | 4.5 QOL score |
| Arm II | Average Quality-of-life | abdominal bloating | 3 QOL score |
| Arm II | Average Quality-of-life | shortness of breath | 3 QOL score |
| Arm II | Average Quality-of-life | abdominal discomfort | 2 QOL score |
Secondary
Number of Paracenteses
We will compare the number of paracenteses between groups. Parametric or nonparametric testing will be used as appropriate.
Time frame: Up to 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm I | Number of Paracenteses | 0.5 number of paracenteses per patient |
| Arm II | Number of Paracenteses | 1 number of paracenteses per patient |