Colorectal Cancer, Depression, Esophageal Cancer, Extrahepatic Bile Duct Cancer, Fatigue, Gallbladder Cancer, Gastric Cancer, Liver Cancer, Lung Cancer, Pancreatic Cancer
Conditions
Keywords
fatigue, psychosocial effects of cancer and its treatment, stage IIIB non-small cell lung cancer, stage IV non-small cell lung cancer, extensive stage small cell lung cancer, advanced adult primary liver cancer, depression, stage III pancreatic cancer, stage IV pancreatic cancer, stage IV esophageal cancer, stage IV gastric cancer, stage IVA colon cancer, stage IVB colon cancer, stage IVA rectal cancer, stage IVB rectal cancer, unresectable gallbladder cancer, unresectable extrahepatic bile duct cancer
Brief summary
RATIONALE: Escitalopram may help improve depression and quality of life in patients with advanced lung or gastrointestinal cancer. It is not yet known whether escitalopram is more effective than a placebo in treating depression in patients with advanced lung or gastrointestinal cancer. PURPOSE: This randomized clinical trial is studying the side effects of escitalopram and to see how well it works compared to a placebo in treating depression in patients with advanced lung or gastrointestinal cancer.
Detailed description
OBJECTIVES: * Compare the efficacy of escitalopram oxalate vs placebo in treating major depressive disorder in patients with advanced lung or gastrointestinal cancer. * Compare the side effect burden of escitalopram oxalate vs placebo in these patients. * Determine potential moderators of the efficacy of escitalopram oxalate in these patients, including medical, psychological, and social variables. OUTLINE: This is a randomized, double-blind, placebo-controlled study. Patients are stratified according to stage of disease (stage IIIB with effusions vs stage IV) and current treatment (radiation vs chemotherapy vs novel agent). Patients are randomized to 1 of 2 treatment arms. * Arm I: Patients receive oral placebo once daily for 4 weeks followed by oral placebo once daily for another 4 weeks * Arm II: Patients receive oral placebo once daily for 4 weeks followed by escitalopram oxalate 10 mg once daily for 4 weeks. * Arm III: Patients receive oral escitalopram oxalate 10 mg once daily for 4 weeks followed by oral placebo once daily for 4 weeks. After 8 weeks, all non-responders are offered open treatment with an antidepressant. Depression, fatigue, quality of life, anxiety, and somatization are assessed at baseline and then at 4 and 8 weeks. PROJECTED ACCRUAL: A total of 220 patients will be accrued for this study.
Interventions
escitalopram oxalate 10 mg once daily for 4 weeks
DRUGPlacebo
one placebo pill identical in appearance to the escitalpram pill once daily
Sponsors
National Cancer Institute (NCI)
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
35 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Diagnosis of any of the following for at least 4 weeks: * Stage IIIB (with effusions) or stage IV non-small cell lung cancer * Extensive stage small cell lung cancer * Stage III or IV pancreatic cancer * Stage IV liver cancer * Stage III or IV gallbladder cancer * Stage III or IV bile duct cancer * Stage IV esophageal cancer * Stage IV gastric cancer * Second line stage IV colorectal cancer * Meets diagnostic and Statistical Manual of Mental Disorders-4th Edition and Endicott criteria for major depressive disorder * Duration of depressive symptoms ≥ 4 weeks * Hamilton Depression D 17 (HAM-D 17) Scale ≥ 14 * No active suicidality requiring immediate care or psychiatric hospitalization PATIENT CHARACTERISTICS: * Able to swallow pills * No active substance abuse disorder (including alcohol abuse within the past 6 months), psychotic disorder or active psychotic symptoms, organic mental disorders, or bipolar disorder * No clinical or laboratory evidence of hypothyroidism * No hypercalcemia * No severe anemia, defined as hemoglobin \< 10 g/dL * No history of multiple adverse drug reactions or allergy to study drugs * Not pregnant * No history of head trauma * No history of epilepsy PRIOR CONCURRENT THERAPY: * No other concurrent antidepressant medications or psychostimulants
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Depression Response Rate of Escitalopram Oxalate 10 mg Once Daily Compared to Placebo Once Daily for Major Depressive Disorder | 4 weeks | Response rate was defined as a 50% reduction in the Hamilton Depression Rating Scale (HAM-D) scores over 4 weeks. The HAM-D can have total scores that range from 0 to 50, with higher scores indicating greater depression. Scores over 14 are considered to be in the depressed range. |
| Change in Hamilton Depression Rating Scale (HAM-D) Scores | 4 weeks | The change in HAM-D scores was calculated by subtracting the score at 4 weeks from the score at baseline. The HAM-D can have total scores that range from 0 to 50, with higher scores indicating greater depression. Scores over 14 are considered to be in the depressed range. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Side Effect Burden | 4 weeks | Side efect burden was defined as the total score of the UKU Side Effects Rating Scale. This scale contains 48 items corresponding to side effects which are rated from 0-3, with 0 meaning not present and 1-3 rating the severity of the side effect. Higher scores represented greater side effect burden. The scale range is 0 to 144. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from the ambulatory thoracic and GI cancer clinics at MGH. Recruitment was open from 11/1/06 until 4/1/11.
Pre-assignment details
After enrollment, participants completed an assessment for major depressive disorder. 90 participants consented for study evaluation. In order to be randomized to a group, participants had to meet criteria for major depressive disorder. Of the 90 evaluated on study, only 24 were randomized.
Participants by arm
| Arm | Count |
|---|---|
| Placebo-Placebo Participants in this arm were randomized to receive placebo for the first 4 weeks and placebo for the second 4 weeks | 8 |
| Placebo-Escitalopram Participants in this arm were randomized to receive placebo for the first 4 weeks and escitalopram for the second 4 weeks | 5 |
| Escitalopram-Placebo Participants in this arm were randomzied to receive escitalopram for the first 4 weeks and placebo for the second 4 weeks | 11 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 1 |
| Overall Study | Death | 1 | 1 | 0 |
| Overall Study | Physician Decision | 1 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 2 | 2 |
Baseline characteristics
| Characteristic | Placebo-Escitalopram | Escitalopram-Placebo | Placebo-Placebo | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 3 Participants | 1 Participants | 5 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 8 Participants | 7 Participants | 19 Participants |
| Age Continuous | 59.40 years STANDARD_DEVIATION 10.84 | 58.36 years STANDARD_DEVIATION 9.41 | 56.63 years STANDARD_DEVIATION 10.51 | 58.00 years STANDARD_DEVIATION 9.68 |
| Region of Enrollment United States | 5 participants | 11 participants | 8 participants | 24 participants |
| Sex: Female, Male Female | 3 Participants | 7 Participants | 4 Participants | 14 Participants |
| Sex: Female, Male Male | 2 Participants | 4 Participants | 4 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 8 | 0 / 5 | 1 / 11 |
| serious Total, serious adverse events | 1 / 8 | 1 / 5 | 0 / 11 |
Outcome results
Primary
Change in Hamilton Depression Rating Scale (HAM-D) Scores
The change in HAM-D scores was calculated by subtracting the score at 4 weeks from the score at baseline. The HAM-D can have total scores that range from 0 to 50, with higher scores indicating greater depression. Scores over 14 are considered to be in the depressed range.
Time frame: 4 weeks
Population: Participants who had at least 1 follow up HAM-D assessment were included. Two participants died, one without a follow up assessment and one with a HAM-D at 2 weeks. For the participant who had the HAM-D at 2 weeks and then died, the last endpoint was carried forward.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo-Placebo | Change in Hamilton Depression Rating Scale (HAM-D) Scores | 6.23 Change in HAM-D scores | Standard Deviation 8.37 |
| Placebo-Escitalopram | Change in Hamilton Depression Rating Scale (HAM-D) Scores | 10.60 Change in HAM-D scores | Standard Deviation 5.18 |
| Escitalopram-Placebo | Change in Hamilton Depression Rating Scale (HAM-D) Scores | 6.45 Change in HAM-D scores | Standard Deviation 5.18 |
Primary
Depression Response Rate of Escitalopram Oxalate 10 mg Once Daily Compared to Placebo Once Daily for Major Depressive Disorder
Response rate was defined as a 50% reduction in the Hamilton Depression Rating Scale (HAM-D) scores over 4 weeks. The HAM-D can have total scores that range from 0 to 50, with higher scores indicating greater depression. Scores over 14 are considered to be in the depressed range.
Time frame: 4 weeks
Population: The efficacy analysis was intent to treat and all randomized participants were analyzed
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Placebo-Placebo | Depression Response Rate of Escitalopram Oxalate 10 mg Once Daily Compared to Placebo Once Daily for Major Depressive Disorder | 3 number of participants with response | 0.52 |
| Placebo-Escitalopram | Depression Response Rate of Escitalopram Oxalate 10 mg Once Daily Compared to Placebo Once Daily for Major Depressive Disorder | 1 number of participants with response | 0.47 |
| Escitalopram-Placebo | Depression Response Rate of Escitalopram Oxalate 10 mg Once Daily Compared to Placebo Once Daily for Major Depressive Disorder | 6 number of participants with response | 0.52 |
Secondary
Side Effect Burden
Side efect burden was defined as the total score of the UKU Side Effects Rating Scale. This scale contains 48 items corresponding to side effects which are rated from 0-3, with 0 meaning not present and 1-3 rating the severity of the side effect. Higher scores represented greater side effect burden. The scale range is 0 to 144.
Time frame: 4 weeks
Population: Participants who completed the 4 week assessment were analyzed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo-Placebo | Side Effect Burden | 3.00 units on a scale | Standard Deviation 2.1 |
| Placebo-Escitalopram | Side Effect Burden | 2.50 units on a scale | Standard Deviation 0.71 |
| Escitalopram-Placebo | Side Effect Burden | 3.44 units on a scale | Standard Deviation 1.88 |