Study of Palliative Care Intervention for Advanced Cancer Patients and Their Caregivers -Educate Nurture Advise Before Life Ends (ENABLE III)

Study Overview
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Brief Summary
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ENABLE III is a randomized clinical trial that evaluates a phone-based palliative care intervention designed to improve quality of life, mood, and symptom management for patients with an advanced stage cancer and their caregivers. The primary aims of this clinical trial are to determine whether a palliative care intervention (introduced immediately or 12 weeks after diagnosis) can improve survival, quality of life, mood, symptom intensity and end-of-life care.

Detailed Description
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In 2008, cancer claimed more than 565,000 American lives -1,500 people a day. Palliative care strives to improve quality of life (QOL) and to prevent bad deaths by providing expert, interdisciplinary care to manage the effects of disease and treatment. Effective end-of-life (EOL) care depends upon proactive, patient-centered interventions to prepare patients and families for the challenges of terminal illness. We were able to demonstrate the feasibility and efficacy of a concurrent oncology palliative care (COPC) intervention in improving quality of life and mood in our previous studies ENABLE I and ENABLE II; however, a number of gaps in our knowledge remain. Patients will be randomized to begin the intervention either immediately or 12 weeks after a new diagnosis of advanced or recurrent cancer. This phone-based intervention consists of: 1) an Advanced Practice Palliative Care Nurse Interventionist instituting 1a) a 6-session manualized patient curriculum- Charting Your Course (CYC), 1b) a 3-session manualized, caregiver curriculum- the Creativity Optimism Planning Expert information (COPE) program, and 1c) on-going patient and caregiver follow up; and 2) Palliative Care Team Comprehensive Assessment & Management.

Official Title
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Early vs. Later Palliative Cancer Care: Clinical and Biobehavioral Outcomes

Conditions
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Advanced Cancer

Intervention / Treatment
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* Behavioral: Later entry group
* Behavioral: Early palliative care intervention


Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA FOR PATIENTS: Able to speak and understand English Over age 18 NEW diagnosis, recurrence, or progression of an advanced stage cancer within THIRTY days of the date the patient was informed of the diagnosis by his/her oncology clinician. Estimated survival of 2 years or less Diagnosed with an advanced stage cancer such as one of the following: Lung Cancer: Stage IIIB or IV non-small cell, or extensive stage small cell Breast Cancer: Stage IV with poor prognostic indicators including but not limited to: a) >2 cytotoxic regimens for MBC; b) diagnosis of MBC less then or equal to 12 months since completion of adjuvant or neoadjuvant treatment; c) triple negative disease (ER/PR - and Her 2-);d) parenchymal brain mets and/or carcinomatous meningitis Gastrointestinal (GI) Cancers: Unresectable stage III or IV Genitourinary (GU) Cancers: Stage IV (for prostate cancer inclusion is limited to persons with hormone refractory prostate cancer) Brain Cancer: Unresectable, Grade IV Melanoma, Stage IV Hematologic Malignancies -Leukemia (e.g. acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML), chronic lymphocytic leukemia (CLL) - advanced stage, treatment refractory, poor prognosis cell type or chromosomal abnormalities, older age -Lymphoma- Stage IV or treatment refractory Hodgkin's disease or non-Hodgkin's lymphoma -Multiple Myeloma - elevated β2-microglobulin, albumin <3.5, PCLI >1%, CRP >6µg/mL, elevated LDH, plasmablastic morphology, abnormal. chromosome 13. Completion of baseline interview INCLUSION CRITERIA FOR PATIENTS FOR BIOMARKER SUB-STUDY: 1. Only patients with lung, breast, GI, GU cancer are eligible INCLUSION CRITERIA FOR CAREGIVERS: Able to read and understand English Anyone identified by the patient as a person who knows you well & is involved in your medical care. PATIENT EXCLUSION CRITERIA: Dementia or significant confusion (Impaired cognitive status as indicated by a score of 3 or less on the Callahan six-item cognitive screening tool 18) Axis I psychiatric diagnosis of severe mental illness (DSM-IV) (e.g. schizophrenia, bipolar disorder, or active substance use disorder) Patients will not be excluded if they do not identify a caregiver Prior involvement with palliative care service within the last year Minimum predicted survival of less than 12 weeks (3 months) PATIENT BIOMARKER SUBSTUDY EXCLUSION CRITERIA: Receiving chronic steroid hormones or unable to schedule specimen collection distant from chemotherapy from steroid pre-medications Unable to come to Norris Cotton Cancer Center (NCCC) for specimen collection times. CAREGIVER EXCLUSION CRITERIA: 1. Unwilling to participate in study.

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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Early entry group<br>Early entry group will begin the intervention at time of diagnosis of advanced cancer | Behavioral: Early palliative care intervention<br>* Advanced Practice Palliative Care Nurse Interventionist instituting a phone-based: a) Charting Your Course (CYC)-Patient Curriculum (6-session manualized); b) Creativity Optimism Planning Expert information(COPE) Caregiver Curriculum (3 session manualized) and c) ongoing contact as determined by the Palliative Care Team assessment/plan; and Comprehensive Palliative Care Team Assessment & Management Plan.<br>|
| Active Comparator: Later entry group<br>Later entry group will begin the intervention 12 weeks after enrollment in the study. | Behavioral: Later entry group<br>* Advanced Practice Palliative Care Nurse Interventionist instituting a phone-based: a) Charting Your Course (CYC)-Patient Curriculum (6-session manualized); b) Creativity Optimism Planning Expert Information (COPE) Caregiver Curriculum (3 session manualized) and c) ongoing contact as determined by the Palliative Care Team assessment/plan; and Comprehensive Palliative Care Team Assessment & Management Plan.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in patient's quality of living over time | Quality of living assessments will include quality of life (QOL), mood, and symptom intensity measures using the following measures: Functional Assessment of Chronic Illness Therapy-Palliative Care (FACIT-Pal): Quality of Life at End of Life (QUAL-E). Center for Epidemiological Study- Depression (CES-D). | baseline, 6,12,18,24,36 and every 12 weeks until death or end of study | 
| Quality of end of life care | End of life (EOL) Care Data Collection Form: This form is used to collect information about the quality of EOL care and circumstances surrounding the last 48 hours of life for patients who die in hospital, nursing home, or home. Quality of Dying and Death Measure (QODD). The QODD is a structured interview conducted with a caregiver to measure the quality of a patient's last week of life. The interview assesses the caregiver's perception of patient symptoms, preferences, and satisfaction with care. | chart review at time of death and caregiver proxy interview 2-3 months after patient death | 
| Estimate and compare the hazard ratios and median survival before and after 1 year from enrollment | We hypothesize that Early entry patients will have longer overall survival at one year compared with Later entry patients. | From enrollment until patient death or end of study | 
| Change in caregiver quality of life, burden and grief over time | Caregiver burden and QOL will be measured using: Quality of Life- Cancer- a self-report measure of QOL for caregivers of patients with cancer. Montgomery Borgatta Caregiver Burden Scale -a self-report measure of caregiver burden. Center for Epidemiological Study- Depression CESD is a measure of depressive symptoms. Functional Assessment of Chronic Illness Therapy - Spiritual Module (FACIT-Sp) - a measure of spiritual well-being developed for persons with chronic illness. Prigerson Inventory of Complicated Grief-Short form (ICG-SF) embedded in the Quality of Death and Dying (QODD). | baseline, 6,12,18,24,36, and every 12 weeks until patient death or end of study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mediating mechanisms and moderators of the concurrent palliative care intervention. | Mediating mechanisms measured will include patient activation, decision support, goal setting, problem solving, care coordination. Moderators measures will include: decision control and treatment goals, self-efficacy, optimism, coping style, social support. | baseline, 6,12,18,24,36 weeks and every 12 weeks until death or end of study | 
| Determine feasibility of enrolling less common solid tumors and hematologic malignancies. | ENABLE II recruited patients only with lung, breast, GI, and GU tumors. We will attempt to also recruit patients with less common poor prognosis solid tumors (e.g. brain) and hematologic malignancies and their caregivers for this concurrent oncology palliative care intervention. | Estimated recruitment period of 2 years | 
| Explore patterns of stress (diurnal salivary and plasma cortisol) and immune biomarkers (lymphocyte subsets and cytokines) | We will explore patterns of stress (diurnal salivary and plasma cortisol) and immune biomarkers (lymphocyte subsets and cytokines)at baseline, 12, and 24 weeks after intervention in a subset of 50 patients with breast, lung, GI, and GU cancer. We hypothesize that stabilized or improved biomarkers of stress and immune function will be evident after Early and Later entry intervention participation. | Baseline, 12, and 24 weeks | 
| Examine the relations among quality of life, mood, symptoms, survival, stress and immune biomarkers. | We hypothesize that higher quality of life,mood, lower symptom intensity, and longer survival will be associated with stable or improved stress and immune biomarkers (e.g. normal plasma cortisol and diurnal salivary cortisol variability, lymphocyte subsets and cytokines | Baseline, 12, and 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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palliative care, end of life care, quality of life, caregivers