Early Palliative Care With Standard Care or Standard Care Alone in Improving Quality of Life of Patients With Incurable Lung or Non-colorectal Gastrointestinal Cancer and Their Family Caregivers

• ClinicalTrials.gov Identifier: NCT02349412
• Recruitment Status: Completed
• First Posted: January 28, 2015
• Results First Posted: February 28, 2019
• Last Update Posted: July 26, 2021
• Sponsor: Alliance for Clinical Trials in Oncology
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Alliance for Clinical Trials in Oncology

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Supportive Care
• Conditions: Liver Cancer; Anxiety Disorder; Depression; Small Cell Lung Cancer; Extrahepatic Bile Duct Cancer; Malignant Mesothelioma; Pancreatic Cancer; Esophageal Cancer; Gastric Cancer; Non-small Cell Lung Cancer
• Intervention: Other: Early palliative care
• Enrollment: 405

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Arm 1 (Early Palliative Care)	Arm 2 (Usual Care)
Arm/Group Description	Patients receive early palliative care and standard oncology care. Patients and family caregivers will be asked to complete quality-of-life questionnaires at weeks 6, 12, and 24. Survival follow-up will be every 4 months from week 24 until death or up to 3 years.	Patients receive standard oncology care. Patient and family caregiver will be asked to complete self-report questionnaires at weeks 6, 12, and 24. Survival follow-up will be every 4 months from week 24 until death or up to 3 years. Palliative care visit only upon request from attending oncologist(s) or patient/family.
Period Title: Overall Study
Started	202	203
Completed Week-12 QOL Assessment Measure	92	101
Completed Week-24 QOL Assessment Measure	68	80
Completed	195	196
Not Completed	7	7
Reason Not Completed
Withdrawal by Subject	7	7

Baseline Characteristics

Arm/Group Title		Arm 1 (Early Palliative Care)	Arm 2 (Usual Care)	Total
Arm/Group Description		Patients receive early palliative care and standard oncology care. Patients and family caregivers will be asked to complete quality-of-life questionnaires at weeks 6, 12, and 24. Survival follow-up will be every 4 months from week 24 until death or up to 3 years.	Patients receive standard oncology care. Patient and family caregiver will be asked to complete self-report questionnaires at weeks 6, 12, and 24. Survival follow-up will be every 4 months from week 24 until death or up to 3 years. Palliative care visit only upon request from attending oncologist(s) or patient/family.	Total of all reporting groups
Overall Number of Baseline Participants		195	196	391
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Full Range); Unit of measure: Years
	Number Analyzed	195 participants	196 participants	391 participants
		65.5; (35 to 97)	65.0; (34 to 92)	65.2; (34 to 97)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	195 participants	196 participants	391 participants
	Female	81 41.5%	89 45.4%	170 43.5%
	Male	114 58.5%	107 54.6%	221 56.5%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	195 participants	196 participants	391 participants
	American Indian or Alaska Native	2 1.0%	2 1.0%	4 1.0%
	Asian	9 4.6%	6 3.1%	15 3.8%
	Native Hawaiian or Other Pacific Islander	0 0.0%	2 1.0%	2 0.5%
	Black or African American	24 12.3%	22 11.2%	46 11.8%
	White	148 75.9%	155 79.1%	303 77.5%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	12 6.2%	9 4.6%	21 5.4%
Region of Enrollment; Measure Type: Count of Participants; Unit of measure: Participants
United States	Number Analyzed	195 participants	196 participants	391 participants
		195 100.0%	196 100.0%	391 100.0%
ECOG Performance Status [1]; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	195 participants	196 participants	391 participants
0		47 24.1%	41 20.9%	88 22.5%
1		108 55.4%	127 64.8%	235 60.1%
2		40 20.5%	28 14.3%	68 17.4%
		[1] Measure Description: Eastern Cooperative Oncology Group PS Scale: 0)Fully active, able to carry on all pre-disease performance without restriction; 1)Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work; 2)Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours; 3)Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours; 4)Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair.

Outcome Measures

1. Primary Outcome

Title	Change in Quality of Life (QOL) From Baseline to Week 12 Per the Functional Assessment of Cancer Therapy-General (FACT-G)
Description	Quality of Life (QOL) was measured using the Functional Assessment of Cancer Therapy-General (FACT-G) on a 0-108 scale, with lower scores corresponding to worse overall QOL and higher scores corresponding to better overall QOL. Change from baseline to week-12 was calculated by subtracting the baseline scores from the scores at week-12. Higher scores on FACT-G indicate better QOL.
Time Frame	Up to 12 weeks

Outcome Measure Data

Analysis Population Description

Only participants with available data on the individual study measure at baseline and 12 weeks were included in the analysis.

Arm/Group Title	Arm 1 (Early Palliative Care)	Arm 2 (Usual Care)
Arm/Group Description:	Patients receive early palliative care and standard oncology care. Patients and family caregivers will be asked to complete quality-of-life questionnaires at weeks 6, 12, and 24. Survival follow-up will be every 4 months from week 24 until death or up to 3 years.	Patients receive standard oncology care. Patient and family caregiver will be asked to complete self-report questionnaires at weeks 6, 12, and 24. Survival follow-up will be every 4 months from week 24 until death or up to 3 years. Palliative care visit only upon request from attending oncologist(s) or patient/family.
Overall Number of Participants Analyzed	92	101
Mean (Standard Deviation); Unit of Measure: units on a scale
	3.35 (14.7)	0.12 (12.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm 1 (Early Palliative Care), Arm 2 (Usual Care)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.104
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	Statistical Method: Available Case ANCOVA Model adjusting for baseline FACT-G score
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	3.23
	Confidence Interval	(2-Sided) 95%; -0.67 to 7.13
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Change in Quality of Life (QOL) From Baseline to Week 24 Per the Functional Assessment of Cancer Therapy-General (FACT-G)
Description	Quality of Life (QOL) was measured using the Functional Assessment of Cancer Therapy-General (FACT-G) on a 0-108 scale, with lower scores corresponding to worse overall QOL and higher scores corresponding to better overall QOL. Change from baseline to week-24 was calculated by subtracting the baseline scores from the scores at week-24. Higher scores on FACT-G indicate better QOL.
Time Frame	Up to 24 weeks

Outcome Measure Data

Analysis Population Description

Only participants with available data on the individual study measure at baseline and 24 weeks were included in the analysis.

Arm/Group Title	Arm 1 (Early Palliative Care)	Arm 2 (Usual Care)
Arm/Group Description:	Patients receive early palliative care and standard oncology care. Patients and family caregivers will be asked to complete quality-of-life questionnaires at weeks 6, 12, and 24. Survival follow-up will be every 4 months from week 24 until death or up to 3 years.	Patients receive standard oncology care. Patient and family caregiver will be asked to complete self-report questionnaires at weeks 6, 12, and 24. Survival follow-up will be every 4 months from week 24 until death or up to 3 years. Palliative care visit only upon request from attending oncologist(s) or patient/family.
Overall Number of Participants Analyzed	68	80
Mean (Standard Deviation); Unit of Measure: units on a scale
	3.80 (15.3)	0.69 (13.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm 1 (Early Palliative Care), Arm 2 (Usual Care)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.188
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	Statistical Method: Available Case ANCOVA Model adjusting for baseline FACT-G score
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	3.12
	Confidence Interval	(2-Sided) 95%; -1.54 to 7.77
	Estimation Comments	[Not Specified]

3. Secondary Outcome

Title	Change in Quality of Life (QOL) From Baseline to Week 12 Per the Hospital Anxiety and Depression Scale (HADS) - Depression
Description	Quality of Life (QOL) was measured using the Hospital Anxiety and Depression Scale (HADS) - Depression on a 0-21 scale, with lower scores corresponding to lower depression and higher scores corresponding to higher depression. Change from baseline to week-12 was calculated by subtracting the baseline scores from the scores at week-12. Lower scores on the HADS-Depression indicate less depression symptoms.
Time Frame	Up to 12 weeks

Outcome Measure Data

Analysis Population Description

Only participants with available data on the individual study measure at baseline and 12 weeks were included in the analysis.

Arm/Group Title	Arm 1 (Early Palliative Care)	Arm 2 (Usual Care)
Arm/Group Description:	Patients receive early palliative care and standard oncology care. Patients and family caregivers will be asked to complete quality-of-life questionnaires at weeks 6, 12, and 24. Survival follow-up will be every 4 months from week 24 until death or up to 3 years.	Patients receive standard oncology care. Patient and family caregiver will be asked to complete self-report questionnaires at weeks 6, 12, and 24. Survival follow-up will be every 4 months from week 24 until death or up to 3 years. Palliative care visit only upon request from attending oncologist(s) or patient/family.
Overall Number of Participants Analyzed	100	112
Mean (Standard Deviation); Unit of Measure: units on a scale
	0.54 (4.0)	0.46 (3.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm 1 (Early Palliative Care), Arm 2 (Usual Care)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.884
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	Statistical Method: Available Case ANCOVA Model adjusting for baseline HADS-Depression score
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.08
	Confidence Interval	(2-Sided) 95%; -0.94 to 2.09
	Estimation Comments	[Not Specified]

4. Secondary Outcome

Title	Change in Quality of Life (QOL) From Baseline to Week 12 Per the Hospital Anxiety and Depression Scale (HADS) - Anxiety
Description	Quality of Life (QOL) was measured using the Hospital Anxiety and Depression Scale (HADS) - Anxiety on a 0-21 scale, with lower scores corresponding to lower anxiety and higher scores corresponding to higher anxiety. Change from baseline to week-12 was calculated by subtracting the baseline scores from the scores at week-12. Lower scores on the HADS-Anxiety indicate less anxiety symptoms.
Time Frame	Up to 12 weeks

Outcome Measure Data

Analysis Population Description

Only participants with available data on the individual study measure at baseline and 12 weeks were included in the analysis.

Arm/Group Title	Arm 1 (Early Palliative Care)	Arm 2 (Usual Care)
Arm/Group Description:	Patients receive early palliative care and standard oncology care. Patients and family caregivers will be asked to complete quality-of-life questionnaires at weeks 6, 12, and 24. Survival follow-up will be every 4 months from week 24 until death or up to 3 years.	Patients receive standard oncology care. Patient and family caregiver will be asked to complete self-report questionnaires at weeks 6, 12, and 24. Survival follow-up will be every 4 months from week 24 until death or up to 3 years. Palliative care visit only upon request from attending oncologist(s) or patient/family.
Overall Number of Participants Analyzed	100	111
Mean (Standard Deviation); Unit of Measure: units on a scale
	-1.13 (2.7)	-0.32 (2.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm 1 (Early Palliative Care), Arm 2 (Usual Care)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.033
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	Statistical Method: Available Case ANCOVA Model adjusting for baseline HADS-Anxiety score
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.81
	Confidence Interval	(2-Sided) 95%; -1.54 to -0.07
	Estimation Comments	[Not Specified]

5. Secondary Outcome

Title	Prognostic Understanding at Week-12 as Measured by "Have You and Your Oncologist Discussed Any Particular Wishes About the Care You Would Want to Receive if You Were Dying?" Question on the Prognosis and Treatment Perceptions Questionnaire
Description	Prognostic Understanding at Week-12 as measured by Prognosis and Treatment Perceptions Questionnaire: "Have you and your oncologist discussed any particular wishes about the care you would want to receive if you were dying?" responses at Week-12 are reported below.
Time Frame	Up to 12 weeks

Outcome Measure Data

Analysis Population Description

Only participants with available data on the individual study measure at week 12 were included in the analysis.

Arm/Group Title	Arm 1 (Early Palliative Care)	Arm 2 (Usual Care)
Arm/Group Description:	Patients receive early palliative care and standard oncology care. Patients and family caregivers will be asked to complete quality-of-life questionnaires at weeks 6, 12, and 24. Survival follow-up will be every 4 months from week 24 until death or up to 3 years.	Patients receive standard oncology care. Patient and family caregiver will be asked to complete self-report questionnaires at weeks 6, 12, and 24. Survival follow-up will be every 4 months from week 24 until death or up to 3 years. Palliative care visit only upon request from attending oncologist(s) or patient/family.
Overall Number of Participants Analyzed	99	110
Measure Type: Count of Participants; Unit of Measure: Participants
Yes	30 30.3%	16 14.5%
No	69 69.7%	94 85.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm 1 (Early Palliative Care), Arm 2 (Usual Care)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.006
	Comments	[Not Specified]
	Method	Chi-squared
	Comments	[Not Specified]

6. Secondary Outcome

Title	Change in QOL on the SF-36 Over Time
Description	[Not Specified]
Time Frame	Up to 3 years

Outcome Measure Data Not Reported

7. Secondary Outcome

Title	Rate of Referral, Enrollment and Length of Stay on Hospice
Description	[Not Specified]
Time Frame	Up to 3 years

Outcome Measure Data Not Reported

8. Secondary Outcome

Title	Location of Death
Description	[Not Specified]
Time Frame	Up to 3 years

Outcome Measure Data Not Reported

9. Secondary Outcome

Title	Number of Hospital and Intensive Care Unit (ICU) Admissions and Days
Description	[Not Specified]
Time Frame	Up to 3 years

Outcome Measure Data Not Reported

10. Secondary Outcome

Title	Chemotherapy and Radiation Administration
Description	[Not Specified]
Time Frame	Up to 3 years

Outcome Measure Data Not Reported

11. Secondary Outcome

Title	Overall Survival
Description	[Not Specified]
Time Frame	Up to 3 years

Outcome Measure Data Not Reported

12. Secondary Outcome

Title	Concordance Between Patient and Family Caregiver Report of Prognosis/Curability
Description	[Not Specified]
Time Frame	Up to 3 years

Outcome Measure Data Not Reported

Adverse Events

Time Frame	Adverse events were not collected for this study.
Adverse Event Reporting Description	Adverse events were not collected for this study.
Arm/Group Title	Arm 1 (Early Palliative Care)	Arm 2 (Usual Care)
Arm/Group Description	Patients receive early palliative care and standard oncology care. Patients and family caregivers will be asked to complete quality-of-life questionnaires at weeks 6, 12, and 24. Survival follow-up will be every 4 months from week 24 until death or up to 3 years.	Patients receive standard oncology care. Patient and family caregiver will be asked to complete self-report questionnaires at weeks 6, 12, and 24. Survival follow-up will be every 4 months from week 24 until death or up to 3 years. Palliative care visit only upon request from attending oncologist(s) or patient/family.
All-Cause Mortality
	Arm 1 (Early Palliative Care)	Arm 2 (Usual Care)
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/0	0/0
Serious Adverse Events
	Arm 1 (Early Palliative Care)	Arm 2 (Usual Care)
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/0	0/0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Arm 1 (Early Palliative Care)	Arm 2 (Usual Care)
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/0	0/0

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

Results Point of Contact

• Name/Title: Jennifer Temel, MD
• Organization: Massachusetts General Hospital Cancer Center
• Phone: (617) 724-0453
• EMail: jtemel@partners.org

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Temel JS, Sloan J, Zemla T, Greer JA, Jackson VA, El-Jawahri A, Kamdar M, Kamal A, Blinderman CD, Strand J, Zylla D, Daugherty C, Furqan M, Obel J, Razaq M, Roeland EJ, Loprinzi C. Multisite, Randomized Trial of Early Integrated Palliative and Oncology Care in Patients with Advanced Lung and Gastrointestinal Cancer: Alliance A221303. J Palliat Med. 2020 Jul;23(7):922-929. doi: 10.1089/jpm.2019.0377. Epub 2020 Feb 7.

Jacobs JM, Shaffer KM, Nipp RD, Fishbein JN, MacDonald J, El-Jawahri A, Pirl WF, Jackson VA, Park ER, Temel JS, Greer JA. Distress is Interdependent in Patients and Caregivers with Newly Diagnosed Incurable Cancers. Ann Behav Med. 2017 Aug;51(4):519-531. doi: 10.1007/s12160-017-9875-3.

• Responsible Party: Alliance for Clinical Trials in Oncology
• ClinicalTrials.gov Identifier: NCT02349412
• Other Study ID Numbers: A221303; U10CA037447 ( U.S. NIH Grant/Contract ); UG1CA189823 ( U.S. NIH Grant/Contract ); NCI-2014-01943 ( Registry Identifier: NCI Clinical Trial Reporting Program Office )
• First Submitted: January 23, 2015
• First Posted: January 28, 2015
• Results First Submitted: February 5, 2019
• Results First Posted: February 28, 2019
• Last Update Posted: July 26, 2021