Clinical trial NCT01245621: Study of Palliative Care Intervention for Advanced Cancer Patients and Their Caregivers -Educate Nurture Advise Before Life Ends (ENABLE III)
Official title: Early vs. Later Palliative Cancer Care: Clinical and Biobehavioral Outcomes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Advanced Cancer
Keywords: palliative care
end of life care
quality of life
caregivers
Lead sponsor: Dartmouth-Hitchcock Medical Center
Sponsor class: OTHER
Collaborators: name: National Institute of Nursing Research (NINR)
First posted: 2010-11-22
Enrollment: 360
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: 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: 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.

Eligibility criteria: INCLUSION CRITERIA FOR PATIENTS:

1. Able to speak and understand English
2. Over age 18
3. 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.
4. Estimated survival of 2 years or less
5. 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.
6. 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:

1. Able to read and understand English
2. Anyone identified by the patient as "a person who knows you well \& is involved in your medical care".

PATIENT EXCLUSION CRITERIA:

1. 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)
2. Axis I psychiatric diagnosis of severe mental illness (DSM-IV) (e.g. schizophrenia, bipolar disorder, or active substance use disorder)
3. Patients will not be excluded if they do not identify a caregiver
4. Prior involvement with palliative care service within the last year
5. Minimum predicted survival of less than 12 weeks (3 months)

PATIENT BIOMARKER SUBSTUDY EXCLUSION CRITERIA:

1. Receiving chronic steroid hormones or unable to schedule specimen collection distant from chemotherapy from steroid pre-medications
2. Unable to come to Norris Cotton Cancer Center (NCCC) for specimen collection times.

CAREGIVER EXCLUSION CRITERIA:

1. Unwilling to participate in study.

Primary outcomes:
measure: Change in patient's quality of living over time
timeFrame: baseline, 6,12,18,24,36 and every 12 weeks until death or end of study
measure: Quality of end of life care
timeFrame: chart review at time of death and caregiver proxy interview 2-3 months after patient death
measure: Estimate and compare the hazard ratios and median survival before and after 1 year from enrollment
timeFrame: From enrollment until patient death or end of study
measure: Change in caregiver quality of life, burden and grief over time
timeFrame: baseline, 6,12,18,24,36, and every 12 weeks until patient death or end of study
Secondary outcomes:
measure: Mediating mechanisms and moderators of the concurrent palliative care intervention.
timeFrame: baseline, 6,12,18,24,36 weeks and every 12 weeks until death or end of study
measure: Determine feasibility of enrolling less common solid tumors and hematologic malignancies.
timeFrame: Estimated recruitment period of 2 years
measure: Explore patterns of stress (diurnal salivary and plasma cortisol) and immune biomarkers (lymphocyte subsets and cytokines)
timeFrame: Baseline, 12, and 24 weeks
measure: Examine the relations among quality of life, mood, symptoms, survival, stress and immune biomarkers.
timeFrame: Baseline, 12, and 24 weeks
Other outcomes:
Locations:
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center - Lebanon
state: New Hampshire
city: Manchester
country: United States
facility: Dartmouth-Hitchcock Clinic - Manchester
state: New Hampshire
city: Nashua
country: United States
facility: St. Joseph Hospital
state: New Hampshire
city: Nashua
country: United States
facility: Dartmouth-Hitchcock NCCC Nashua
state: New Hampshire
city: Providence
country: United States
facility: Providence VA Medical Center
state: Rhode Island
city: Berlin
country: United States
facility: Mountainview Medical
state: Vermont
city: White River Junction
country: United States
facility: Veteran's Administration Hospital
state: Vermont
Study officials:
affiliation: Dartmouth-Hitchcock Medical Center
name: Marie A. Bakitas, DNSc, APRN
role: PRINCIPAL_INVESTIGATOR
affiliation: Dartmouth-Hitchcock Medical Center
name: Jennifer P. Frost, RN, MS
role: STUDY_DIRECTOR
References:
citation: O'Hara RE, Hull JG, Lyons KD, Bakitas M, Hegel MT, Li Z, Ahles TA. Impact on caregiver burden of a patient-focused palliative care intervention for patients with advanced cancer. Palliat Support Care. 2010 Dec;8(4):395-404. doi: 10.1017/S1478951510000258. Epub 2010 Sep 28.
citation: Bakitas M, Stevens M, Ahles T, Kirn M, Skalla K, Kane N, Greenberg ER; Project Enable Co-Investigators. Project ENABLE: a palliative care demonstration project for advanced cancer patients in three settings. J Palliat Med. 2004 Apr;7(2):363-72. doi: 10.1089/109662104773709530.
citation: Bakitas M, Ahles TA, Skalla K, Brokaw FC, Byock I, Hanscom B, Lyons KD, Hegel MT; ENABLE project team. Proxy perspectives regarding end-of-life care for persons with cancer. Cancer. 2008 Apr 15;112(8):1854-61. doi: 10.1002/cncr.23381.
citation: Bakitas M, Lyons KD, Hegel MT, Balan S, Barnett KN, Brokaw FC, Byock IR, Hull JG, Li Z, McKinstry E, Seville JL, Ahles TA. The project ENABLE II randomized controlled trial to improve palliative care for rural patients with advanced cancer: baseline findings, methodological challenges, and solutions. Palliat Support Care. 2009 Mar;7(1):75-86. doi: 10.1017/S1478951509000108.
citation: Bakitas M, Lyons KD, Hegel MT, Balan S, Brokaw FC, Seville J, Hull JG, Li Z, Tosteson TD, Byock IR, Ahles TA. Effects of a palliative care intervention on clinical outcomes in patients with advanced cancer: the Project ENABLE II randomized controlled trial. JAMA. 2009 Aug 19;302(7):741-9. doi: 10.1001/jama.2009.1198.
citation: Lyons KD, Bakitas M, Hegel MT, Hanscom B, Hull J, Ahles TA. Reliability and validity of the Functional Assessment of Chronic Illness Therapy-Palliative care (FACIT-Pal) scale. J Pain Symptom Manage. 2009 Jan;37(1):23-32. doi: 10.1016/j.jpainsymman.2007.12.015. Epub 2008 May 27.
citation: Ryan RE, Connolly M, Bradford NK, Henderson S, Herbert A, Schonfeld L, Young J, Bothroyd JI, Henderson A. Interventions for interpersonal communication about end of life care between health practitioners and affected people. Cochrane Database Syst Rev. 2022 Jul 8;7(7):CD013116. doi: 10.1002/14651858.CD013116.pub2.
citation: Corn BW, Feldman DB, Hull JG, O'Rourke MA, Bakitas MA. Dispositional hope as a potential outcome parameter among patients with advanced malignancy: An analysis of the ENABLE database. Cancer. 2022 Jan 15;128(2):401-409. doi: 10.1002/cncr.33907. Epub 2021 Oct 6.
citation: Prescott AT, Hull JG, Dionne-Odom JN, Tosteson TD, Lyons KD, Li Z, Li Z, Dragnev KH, Hegel MT, Steinhauser KE, Ahles TA, Bakitas MA. The role of a palliative care intervention in moderating the relationship between depression and survival among individuals with advanced cancer. Health Psychol. 2017 Dec;36(12):1140-1146. doi: 10.1037/hea0000544. Epub 2017 Oct 19.
citation: Bagcivan G, Dionne-Odom JN, Frost J, Plunkett M, Stephens LA, Bishop P, Taylor RA, Li Z, Tucker R, Bakitas M. What happens during early outpatient palliative care consultations for persons with newly diagnosed advanced cancer? A qualitative analysis of provider documentation. Palliat Med. 2018 Jan;32(1):59-68. doi: 10.1177/0269216317733381. Epub 2017 Sep 27.
citation: Bakitas MA, Tosteson TD, Li Z, Lyons KD, Hull JG, Li Z, Dionne-Odom JN, Frost J, Dragnev KH, Hegel MT, Azuero A, Ahles TA. Early Versus Delayed Initiation of Concurrent Palliative Oncology Care: Patient Outcomes in the ENABLE III Randomized Controlled Trial. J Clin Oncol. 2015 May 1;33(13):1438-45. doi: 10.1200/JCO.2014.58.6362. Epub 2015 Mar 23.
citation: Dionne-Odom JN, Azuero A, Lyons KD, Hull JG, Tosteson T, Li Z, Li Z, Frost J, Dragnev KH, Akyar I, Hegel MT, Bakitas MA. Benefits of Early Versus Delayed Palliative Care to Informal Family Caregivers of Patients With Advanced Cancer: Outcomes From the ENABLE III Randomized Controlled Trial. J Clin Oncol. 2015 May 1;33(13):1446-52. doi: 10.1200/JCO.2014.58.7824. Epub 2015 Mar 23.