Escitalopram in Treating Depression in Patients With Advanced Lung or Gastrointestinal Cancer

• Sponsor: Massachusetts General Hospital (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00387348
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 24
• Location: 1
• Arms: 3
• Duration (Months): 61
• Patients Per Site Per Month: 0.4

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer; Depression; Esophageal Cancer; Extrahepatic Bile Duct Cancer; Fatigue; Gallbladder Cancer; Gastric Cancer; Liver Cancer; Lung Cancer; Pancreatic Cancer	Drug: escitalopram oxalate; Drug: Placebo	Phase 3

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Supportive Care
• Official Title: Symptom Management Trial in Cancer Survivors
• Study Start Date: Mar 1, 2006
• Actual Primary Completion Date: Apr 1, 2011
• Actual Study Completion Date: Apr 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo-Placebo Participants in this arm were randomized to receive placebo once daily for the first 4 weeks and placebo once daily for the second 4 weeks	Drug: Placebo; one placebo pill identical in appearance to the escitalpram pill once daily
Other: Placebo-Escitalopram Participants in this arm were randomized to receive placebo once daily for the first 4 weeks and escitalopram oxalate 10 mg once daily for the second 4 weeks	Drug: escitalopram oxalate; escitalopram oxalate 10 mg once daily for 4 weeks; Drug: Placebo; one placebo pill identical in appearance to the escitalpram pill once daily
Other: Escitalopram-Placebo Participants in this arm were randomzied to receive escitalopram 10 mg once daily for the first 4 weeks and placebo once daily for the second 4 weeks	Drug: escitalopram oxalate; escitalopram oxalate 10 mg once daily for 4 weeks; Drug: Placebo; one placebo pill identical in appearance to the escitalpram pill once daily

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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 Outcome Measures

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 35 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02114

Sponsors and Collaborators

• Massachusetts General Hospital
• National Cancer Institute (NCI)

Investigators

• Study Chair: William F. Pirl, MD, Massachusetts General Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: William Pirl, Principal Investigator, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT00387348
• Other Study ID Numbers: CDR0000505774; MGH-2006-P-000299; K23CA115908
• First Posted: Oct 13, 2006
• Last Update Posted: Dec 3, 2012
• Last Verified: Nov 1, 2012

• Keywords provided by William Pirl, Principal Investigator, Massachusetts General Hospital: 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
• Additional relevant MeSH terms: Lung Neoplasms; Pancreatic Neoplasms; Stomach Neoplasms; Esophageal Neoplasms; Liver Neoplasms; Gallbladder Neoplasms; Bile Duct Neoplasms; Cholangiocarcinoma; Fatigue; Depression; Depressive Disorder; Dexetimide; Citalopram

Study Results

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 Detail	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.

Arm/Group Title	Placebo-Placebo	Placebo-Escitalopram	Escitalopram-Placebo
Arm/Group Description	Participants in this arm were randomized to receive placebo once daily by mouth for the first 4 weeks and placebo once daily by mouth for the second 4 weeks.	Participants in this arm were randomized to receive placebo once daily by mouth for the first 4 weeks and escitalopram 10 mg once daily by mouth for the second 4 weeks	Participants in this arm were randomzied to receive escitalopram 10 mg once daily by mouth for the first 4 weeks and placebo once daily by mouth for the second 4 weeks
Period Title: Overall Study
STARTED	8	5	11
COMPLETED	5	2	7
NOT COMPLETED	3	3	4

Baseline Characteristics

Arm/Group Title	Placebo-Placebo	Placebo-Escitalopram	Escitalopram-Placebo	Total
Arm/Group Description	Participants in this arm were randomized to receive placebo for the first 4 weeks and placebo for the second 4 weeks	Participants in this arm were randomized to receive placebo for the first 4 weeks and escitalopram for the second 4 weeks	Participants in this arm were randomzied to receive escitalopram for the first 4 weeks and placebo for the second 4 weeks	Total of all reporting groups
Overall Participants	8	5	11	24
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	7 87.5%	4 80%	8 72.7%	19 79.2%
>=65 years	1 12.5%	1 20%	3 27.3%	5 20.8%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.63 (10.51)	59.40 (10.84)	58.36 (9.41)	58.00 (9.68)
Sex: Female, Male (Count of Participants)
Female	4 50%	3 60%	7 63.6%	14 58.3%
Male	4 50%	2 40%	4 36.4%	10 41.7%
Region of Enrollment (participants) [Number]
United States	8 100%	5 100%	11 100%	24 100%

Outcome Measures

1. Primary Outcome

Title	Depression Response Rate of Escitalopram Oxalate 10 mg Once Daily Compared to Placebo Once Daily for Major Depressive Disorder
Description	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

Outcome Measure Data

Analysis Population Description

The efficacy analysis was intent to treat and all randomized participants were analyzed

Arm/Group Title	Placebo-Placebo	Placebo-Escitalopram	Escitalopram-Placebo
Arm/Group Description	Participants in this arm were randomized to receive placebo once daily by mouth for the first 4 weeks and placebo oncedaily by mouth for the second 4 weeks	Participants in this arm were randomized to receive placebo once daily by mouth for the first 4 weeks and escitalopram 10 mg once daily by mouth for the second 4 weeks	Participants in this arm were randomzied to receive escitalopram f10 mg once daily by mouth or the first 4 weeks and placebo once daily by mouth for the second 4 weeks
Measure Participants	8	5	11
Number [number of participants with response]	3 (0.52) 37.5%	1 (0.47) 20%	6 (0.52) 54.5%

2. Secondary Outcome

Title	Side Effect Burden
Description	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

Outcome Measure Data

Analysis Population Description

Participants who completed the 4 week assessment were analyzed

Arm/Group Title	Placebo-Placebo	Placebo-Escitalopram	Escitalopram-Placebo
Arm/Group Description	Participants in this arm were randomized to receive placebo for the first 4 weeks and placebo for the second 4 weeks	Participants in this arm were randomized to receive placebo for the first 4 weeks and escitalopram for the second 4 weeks	Participants in this arm were randomzied to receive escitalopram for the first 4 weeks and placebo for the second 4 weeks
Measure Participants	6	2	9
Mean (Standard Deviation) [units on a scale]	3.00 (2.10)	2.50 (0.71)	3.44 (1.88)

3. Primary Outcome

Title	Change in Hamilton Depression Rating Scale (HAM-D) Scores
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Placebo-Placebo	Placebo-Escitalopram	Escitalopram-Placebo
Arm/Group Description	Participants in this arm were randomized to receive placebo once daily by mouth for the first 4 weeks and placebo once daily by mouth for the second 4 weeks	Participants in this arm were randomized to receive placebo once daily by mouth for the first 4 weeks and escitalopram 10 mg once daily by mouth for the second 4 weeks	Participants in this arm were randomzied to receive escitalopram 10 mg once daily by mouth for the first 4 weeks and placebo once daily by mouth for the second 4 weeks
Measure Participants	7	5	11
Mean (Standard Deviation) [Change in HAM-D scores]	6.23 (8.37)	10.60 (5.18)	6.45 (5.18)

Adverse Events

Arm/Group Title	Placebo-Placebo		Placebo-Escitalopram		Escitalopram-Placebo
Arm/Group Description	Participants in this arm were randomized to receive placebo for the first 4 weeks and placebo for the second 4 weeks		Participants in this arm were randomized to receive placebo for the first 4 weeks and escitalopram for the second 4 weeks		Participants in this arm were randomzied to receive escitalopram for the first 4 weeks and placebo for the second 4 weeks
All Cause Mortality
	Placebo-Placebo		Placebo-Escitalopram		Escitalopram-Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo-Placebo		Placebo-Escitalopram		Escitalopram-Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/8 (12.5%)		1/5 (20%)		0/11 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
death	1/8 (12.5%)	1	1/5 (20%)	1	0/11 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo-Placebo		Placebo-Escitalopram		Escitalopram-Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/8 (12.5%)		0/5 (0%)		1/11 (9.1%)
Psychiatric disorders
HAM-D score increased by at least 25%	1/8 (12.5%)	1	0/5 (0%)	0	1/11 (9.1%)	1

Limitations/Caveats

After an interim analaysis, the DSMB decided to terminate the trial early because of the rate of adverse events (HAM-D scores increasing by at least 25%) and deaths were higher in participants receiving placebo.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.