Metastatic Cancer
Conditions
Brief summary
The current study is designed to test nationally whether patients' outcomes and utilization of services can be improved through symptom monitoring via patient-reported outcomes between visits.
Detailed description
This is a cluster RCT at approximately 50 sites where randomization will occur in a 1:1 ratio at the site level (not at the individual patient level). Therefore, approximately 25 sites will be randomized to the PRO-TECT intervention arm (patient-reporting of symptoms), and approximately 25 sites will be randomized to the control arm (usual care delivery). Approximately 1200 patients will be enrolled. Specifically: PROCEDURES AT ALL SITES (CONTROL SITES AND INTERVENTION SITES): * Site staff (CRA and Nurse Champion required) will attend the site initiation webinar with UNC staff, including training for the PRO-Core online data management system and orientation to the symptom management guidelines. * At enrollment, all participants will be given a booklet with patient-level symptom advice and a link to the content online. * All participants will receive compensation for participation, mailed to them as gift cards by UNC. * CRAs will train all participants how to complete outcomes questionnaires for the trial using the PRO-Core online system. Participants will be given a choice to complete these in clinic or from home online, or if necessary via paper in clinic (with the CRA entering the data into PRO-Core). If the patient does not self-complete this information, the CRA will contact them to collect the information and then enter it into PRO-Core. The outcomes questionnaires will be completed at baseline; and at month 1 (+/- 2 weeks); and at months 3, 6, 9, and 12/off-study (+/- 4 weeks each), and will be available in English, Spanish, or Mandarin Chinese. At each time point, the CRA will contact the participant to remind them about the upcoming questionnaire and offer help. * Chart abstraction will be conducted by CRAs at baseline and at off-study for each participant, with data entered into the PRO-Core system. Date of death information will additionally be abstracted at 18 and 24 months, and possibly later per the UNC study team. * CRAs will be asked to complete a feedback survey (entered by the CRA into the PRO-Core online system) and may be asked to participate in a brief telephone debriefing and/or site visit. * Accrual will be monitored in a weekly teleconference between the UNC team and site CRAs. ADDITIONAL PROCEDURES AT INTERVENTION SITES ONLY: * At baseline, CRAs will also train patients to self-report symptoms and physical functioning using the PRO-Core system weekly for up to a year, with a choice to do this online or via an automated telephone system (patient choice), and a choice of English, Spanish, or Mandarin Chinese. * Whenever a concerning symptom is reported, an automated email alert notification will be sent to the site CRA. The CRA will forward the email alert to the responsible clinical nurse (or other covering clinician) and CC the site's Nurse Champion. Within 72 hours, the CRA will document what action(s), if any, were taken by the nurse in response to the alert (entered by the CRA into a form in the PRO-Core system). * A symptom report will be printed/generated by the site CRA whenever the patient has a clinic visit, and will be given to the oncologist and nurse caring for the patient.
Interventions
At baseline, CRAs will train patients to self-report symptoms and physical functioning weekly for up to a year, with a choice to do so online or via an automated telephone system. Whenever a concerning symptom is reported, an automated email alert notification will be sent to the site CRA. The CRA will forward the alert to the responsible clinical nurse (or other covering clinician) and CC the site's Nurse Champion. Within 72 hours, the CRA will document what action(s), if any, were taken by the nurse in response to the alert (entered by the CRA into a form in the PRO-Core system). A symptom report will be printed/generated by the site CRA whenever the patient has a clinic visit and will be given to the oncologist and nurse caring for the patient.
OTHERUsual Care Delivery
Patients receive routine cancer care delivery with no additional systematic monitoring of symptoms
Sponsors
Patient-Centered Outcomes Research Institute
University of North Carolina
Mayo Clinic
American Society of Clinical Oncology
American Cancer Society, Inc.
Dana-Farber Cancer Institute
Alliance Foundation Trials, LLC.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
HEALTH_SERVICES_RESEARCH
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
1. Adults (21+) with metastatic cancer of any type (EXCEPT leukemia or indolent \[slow growing\] lymphoma) 2. Receiving outpatient systemic cancer treatment for non-curative/palliative intent, including chemotherapy, targeted therapy, or immunotherapy. 3. Enrolled at any point in their treatment trajectory, meaning during any line of treatment, and at any point during a course or cycle of treatment. 4. Can understand English, Spanish, and/or Mandarin Chinese.
Exclusion criteria
1. Cognitive deficits that would preclude understanding of consent form and/or questionnaires. 2. Current participation in a therapeutic clinical trial (because these often involve PRO questionnaires and intensive monitoring). 3. Patients being treated with curative intent (e.g., adjuvant chemotherapy for breast, lung, or ovarian cancer; primary curative therapy for testis cancer or lymphoma). 4. Receiving hormonal therapy only (e.g., tamoxifen or aromatase inhibitors in breast cancer; androgen deprivation therapy in prostate cancer; or octreotide in neuroendocrine cancers) 5. Indolent lymphomas (due to their prolonged time courses that may be minimally symptomatic). 6. Leukemias (time courses inconsistent with other tumor types in chronic and acute leukemias). 7. Does not understand English, Spanish, or Mandarin Chinese.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | 24 months | Unadjusted Kaplan-Meier estimated survival, based on administrative datasets and practice self-report/medical records. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Physical Functioning | Month 3 | Physical functioning was measured at the 3 month time point using the European Organisation for Research and Treatment of Cancer QLQ-C30 questionnaire. The QLQ-C30 is a widely used 30 item questionnaire with excellent measurement properties. Physical functioning was assessed via 5 items from the QLQ-C30 which generated a single score on a 0-100 point scale (higher scores are better). Mean changes from baseline were measured using the QLQ-C30 at 3 months and compared between arms with a linear combination of parameters from a general linear mixed model. Patients who completed the QLQ C30 at baseline and each follow up time point were categorized as improved on each outcome if their score increased by \>/=5 points from baseline; worse if their score decreased by \>/=5 points and otherwise as stable. |
| Symptom Control | Month 3 | Symptom control was measured at the 3 month time point using the European Organisation for Research and Treatment of Cancer QLQ-C30 questionnaire. The QLQ-C30 is a widely used 30 item questionnaire with excellent measurement properties. Symptom control was assessed as a composite of 8 QLQ-C30 symptom scale scores on a 0-100 point scale (higher scores are better). Mean changes from baseline were measured using the QLQ-C30 at 3 months and compared between arms with a linear combination of parameters from a general linear mixed model. Patients who completed the QLQ C30 at baseline and each follow up time point were categorized as improved on each outcome if their score increased by \>/=5 points from baseline; worse if their score decreased by \>/=5 points and otherwise as stable. |
| Health-related Quality of Life | Month 3 | Health-related quality of life was measured at the 3 month time point using the European Organisation for Research and Treatment of Cancer QLQ-C30 questionnaire. The QLQ-C30 is a widely used 30 item questionnaire with excellent measurement properties. Health-related quality of life was assessed as a composite of function and symptom scale scores on a 0-100 point scale (higher scores are better). Mean changes from baseline were measured using the QLQ-C30 at 3 months and compared between arms with a linear combination of parameters from a general linear mixed model. Patients who completed the QLQ C30 at baseline and each follow up time point were categorized as improved on each outcome if their score increased by \>/=5 points from baseline; worse if their score decreased by \>/=5 points and otherwise as stable. |
| Patient Satisfaction/Communication | Month 3 | Patients in the ePRO arm were measured via Patient Satisfaction Questionnaire assessing comprehension of ePRO questions, usability of digital ePRO system, meaningfulness/relevance of ePRO questions, communication/actionability with care team, clinical utility of ePRO system and patient self efficacy. The number of patients analyzed is the number of patients who completed the questions. Some questions were not administered to all patients. |
| Emergency Department Utilization | 1 year | Data for emergency department visits were obtained from data abstracted at each practice from the electronic medical record. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited at 52 community oncology practices across 25 states between October 2017 and March 2020. The first participant was enrolled on October 30, 2017 and the last participant was enrolled on March 16, 2020. Enrollment was halted short of the enrollment goal of 1200 participants due the uncertainties of the COVID 19 pandemic.
Pre-assignment details
1444 participants were assessed for eligibility and 247 were excluded for the following reasons: 93 did not meet the inclusion criteria 154 declined to participate (1 not enough time to consent, 36 study would take up too much time, 11 patient too sick, 2 patient functional limitations, 41 did not want to fill out survey, 8 did not want contact between visits, 55 no reason given)
Participants by arm
| Arm | Count |
|---|---|
| ePRO Intervention Patients report symptoms weekly via web or automated telephone system (electronic patient reported outcomes (ePROs)). Email alerts to nurses for severe/worsening symptoms; printouts for clinicians at visits. Evidence based symptom management pathways provided to patients and clinicians. | 593 |
| Usual Care Control Evidence-based symptom management pathways provided to patients and clinicians
Usual Care Control: Patients receive routine cancer care delivery with no additional systematic monitoring of symptoms | 598 |
| Total | 1,191 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| 12 Month Time Point | Changed oncology practice | 20 | 9 |
| 12 Month Time Point | Death, hospice, discontinued therapy | 172 | 175 |
| 12 Month Time Point | Voluntary withdrawal | 35 | 4 |
| 3 Month Time Point | Changed oncology practice | 4 | 2 |
| 3 Month Time Point | Death, hospice, discontinued therapy | 41 | 37 |
| 3 Month Time Point | Voluntary withdrawal | 6 | 3 |
| Enrollment | Excluded after randomization for ineligibility | 4 | 2 |
Baseline characteristics
| Characteristic | ePRO Intervention | Usual Care Control | Total |
|---|---|---|---|
| Age, Customized | 64 years | 62 years | 63 years |
| Cancer Type Breast | 97 Participants | 80 Participants | 177 Participants |
| Cancer Type Colorectal, anal | 100 Participants | 132 Participants | 232 Participants |
| Cancer Type Gastroesophageal, Small bowel | 25 Participants | 38 Participants | 63 Participants |
| Cancer Type Genitourinary Non-prostate (Bladder, Kidney, Testicular, Penile) | 36 Participants | 26 Participants | 62 Participants |
| Cancer Type Gyn (Ovarian, Cervix, Uterine, Vaginal) | 64 Participants | 53 Participants | 117 Participants |
| Cancer Type Melanoma, Skin | 11 Participants | 21 Participants | 32 Participants |
| Cancer Type Myeloma, Lymphoma | 31 Participants | 31 Participants | 62 Participants |
| Cancer Type Other (Brain, Sarcoma, Other Soft Tissue, Head/Neck, Unknown Primary) | 30 Participants | 40 Participants | 70 Participants |
| Cancer Type Pancreas, Hepatobiliary | 48 Participants | 49 Participants | 97 Participants |
| Cancer Type Prostate | 33 Participants | 18 Participants | 51 Participants |
| Cancer Type Thoracic (Lung, Thyroid, Thymus) | 118 Participants | 110 Participants | 228 Participants |
| Difficulty Paying Bills Missing | 1 Participants | 2 Participants | 3 Participants |
| Difficulty Paying Bills Not at all | 260 Participants | 224 Participants | 484 Participants |
| Difficulty Paying Bills Not very | 106 Participants | 127 Participants | 233 Participants |
| Difficulty Paying Bills Somewhat | 161 Participants | 184 Participants | 345 Participants |
| Difficulty Paying Bills Very/extremely | 65 Participants | 61 Participants | 126 Participants |
| Education 1st-8th Grade | 10 Participants | 14 Participants | 24 Participants |
| Education 9th-11th Grade | 35 Participants | 49 Participants | 84 Participants |
| Education Advanced Degree | 65 Participants | 50 Participants | 115 Participants |
| Education College Degree | 91 Participants | 93 Participants | 184 Participants |
| Education High School Graduate/GED | 173 Participants | 187 Participants | 360 Participants |
| Education Missing | 1 Participants | 2 Participants | 3 Participants |
| Education Some College, Associate's Degree, Other Certification | 218 Participants | 203 Participants | 421 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 14 Participants | 39 Participants | 53 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 577 Participants | 557 Participants | 1134 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 4 Participants |
| Line of Cancer Therapy 1st Line | 207 Participants | 237 Participants | 444 Participants |
| Line of Cancer Therapy 2nd Line | 176 Participants | 192 Participants | 368 Participants |
| Line of Cancer Therapy 3rd Line | 102 Participants | 89 Participants | 191 Participants |
| Line of Cancer Therapy 4th Line | 108 Participants | 80 Participants | 188 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 11 Participants | 13 Participants | 24 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 16 Participants | 18 Participants |
| Race (NIH/OMB) Black or African American | 99 Participants | 94 Participants | 193 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants | 22 Participants | 27 Participants |
| Race (NIH/OMB) White | 473 Participants | 452 Participants | 925 Participants |
| Sex/Gender, Customized Female | 359 Participants | 335 Participants | 694 Participants |
| Sex/Gender, Customized Male | 234 Participants | 262 Participants | 496 Participants |
| Sex/Gender, Customized Missing | 0 Participants | 1 Participants | 1 Participants |
| Urban or Rural Site Participants at Rural Site | 154 Participants | 163 Participants | 317 Participants |
| Urban or Rural Site Participants at Urban Site | 439 Participants | 435 Participants | 874 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 350 / 593 | 345 / 598 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
Overall Survival
Unadjusted Kaplan-Meier estimated survival, based on administrative datasets and practice self-report/medical records.
Time frame: 24 months
Population: Enrolled eligible patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ePRO Intervention | Overall Survival | 42.0 percentage of participants |
| Usual Care Control | Overall Survival | 43.5 percentage of participants |
Secondary
Emergency Department Utilization
Data for emergency department visits were obtained from data abstracted at each practice from the electronic medical record.
Time frame: 1 year
Population: Enrolled eligible patients
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ePRO Intervention | Emergency Department Utilization | No (0) ED Visits | 315 Participants |
| ePRO Intervention | Emergency Department Utilization | 1+ ED Visits | 278 Participants |
| Usual Care Control | Emergency Department Utilization | No (0) ED Visits | 273 Participants |
| Usual Care Control | Emergency Department Utilization | 1+ ED Visits | 325 Participants |
Secondary
Health-related Quality of Life
Health-related quality of life was measured at the 3 month time point using the European Organisation for Research and Treatment of Cancer QLQ-C30 questionnaire. The QLQ-C30 is a widely used 30 item questionnaire with excellent measurement properties. Health-related quality of life was assessed as a composite of function and symptom scale scores on a 0-100 point scale (higher scores are better). Mean changes from baseline were measured using the QLQ-C30 at 3 months and compared between arms with a linear combination of parameters from a general linear mixed model. Patients who completed the QLQ C30 at baseline and each follow up time point were categorized as improved on each outcome if their score increased by \>/=5 points from baseline; worse if their score decreased by \>/=5 points and otherwise as stable.
Time frame: Month 3
Population: Patients who completed the QLQ-C30 measure at the 3-month time point.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ePRO Intervention | Health-related Quality of Life | Improved Health-related Quality of Life (score increased >/=5 points from baseline) | 191 Participants |
| ePRO Intervention | Health-related Quality of Life | Non-responder for Health-related Quality of Life (score changed <5 points from baseline) | 199 Participants |
| ePRO Intervention | Health-related Quality of Life | Worsened Health-related Quality of Life (score decreased >/=5 points from baseline) | 127 Participants |
| Usual Care Control | Health-related Quality of Life | Improved Health-related Quality of Life (score increased >/=5 points from baseline) | 154 Participants |
| Usual Care Control | Health-related Quality of Life | Non-responder for Health-related Quality of Life (score changed <5 points from baseline) | 229 Participants |
| Usual Care Control | Health-related Quality of Life | Worsened Health-related Quality of Life (score decreased >/=5 points from baseline) | 160 Participants |
Secondary
Patient Satisfaction/Communication
Patients in the ePRO arm were measured via Patient Satisfaction Questionnaire assessing comprehension of ePRO questions, usability of digital ePRO system, meaningfulness/relevance of ePRO questions, communication/actionability with care team, clinical utility of ePRO system and patient self efficacy. The number of patients analyzed is the number of patients who completed the questions. Some questions were not administered to all patients.
Time frame: Month 3
Population: Patients participating in the ePROs arm completed the Patient Feedback Survey to assess patient satisfaction with the system and communication with their care team.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ePRO Intervention | Patient Satisfaction/Communication | Patients who strongly or somewhat agree that the ePRO system was easy to use | 472 participants |
| ePRO Intervention | Patient Satisfaction/Communication | Patients who strongly or somewhat agree that ePRO survey questions were easy to understand | 480 participants |
| ePRO Intervention | Patient Satisfaction/Communication | Patients who strongly or somewhat agree the ePRO survey questions were relevant to them | 359 participants |
| ePRO Intervention | Patient Satisfaction/Communication | Patients who strongly or somewhat agree the process improved discussions with their care team | 365 participants |
| ePRO Intervention | Patient Satisfaction/Communication | Patients who strongly or somewhat agree that their doctor/nurse used the symptom information | 353 participants |
| ePRO Intervention | Patient Satisfaction/Communication | Self-reporting symptoms weekly from home made them feel more in control of their care | 387 participants |
| ePRO Intervention | Patient Satisfaction/Communication | Patients who strongly or somewhat agree they would recommend the ePRO system to other patients | 452 participants |
Secondary
Physical Functioning
Physical functioning was measured at the 3 month time point using the European Organisation for Research and Treatment of Cancer QLQ-C30 questionnaire. The QLQ-C30 is a widely used 30 item questionnaire with excellent measurement properties. Physical functioning was assessed via 5 items from the QLQ-C30 which generated a single score on a 0-100 point scale (higher scores are better). Mean changes from baseline were measured using the QLQ-C30 at 3 months and compared between arms with a linear combination of parameters from a general linear mixed model. Patients who completed the QLQ C30 at baseline and each follow up time point were categorized as improved on each outcome if their score increased by \>/=5 points from baseline; worse if their score decreased by \>/=5 points and otherwise as stable.
Time frame: Month 3
Population: Patients who completed the QLQ C30 measure at the 3 month time point.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ePRO Intervention | Physical Functioning | Improved Physical Functioning (score increased >/=5 points from baseline) | 227 Participants |
| ePRO Intervention | Physical Functioning | Worsened Physical Functioning (score decreased >/=5 points from baseline) | 162 Participants |
| ePRO Intervention | Physical Functioning | Non-responder for Physical Functioning (score changed <5 points from baseline) | 133 Participants |
| Usual Care Control | Physical Functioning | Non-responder for Physical Functioning (score changed <5 points from baseline) | 147 Participants |
| Usual Care Control | Physical Functioning | Improved Physical Functioning (score increased >/=5 points from baseline) | 195 Participants |
| Usual Care Control | Physical Functioning | Worsened Physical Functioning (score decreased >/=5 points from baseline) | 202 Participants |
Secondary
Symptom Control
Symptom control was measured at the 3 month time point using the European Organisation for Research and Treatment of Cancer QLQ-C30 questionnaire. The QLQ-C30 is a widely used 30 item questionnaire with excellent measurement properties. Symptom control was assessed as a composite of 8 QLQ-C30 symptom scale scores on a 0-100 point scale (higher scores are better). Mean changes from baseline were measured using the QLQ-C30 at 3 months and compared between arms with a linear combination of parameters from a general linear mixed model. Patients who completed the QLQ C30 at baseline and each follow up time point were categorized as improved on each outcome if their score increased by \>/=5 points from baseline; worse if their score decreased by \>/=5 points and otherwise as stable.
Time frame: Month 3
Population: Patients who completed the QLQ-C30 measure at the 3-month time point.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ePRO Intervention | Symptom Control | Improved Symptom Control (score increased >/=5 points from baseline) | 195 Participants |
| ePRO Intervention | Symptom Control | Non-responder for Symptom Control (score changed <5 points from baseline) | 199 Participants |
| ePRO Intervention | Symptom Control | Worsened Symptom Control (score decreased >/=5 points from baseline) | 123 Participants |
| Usual Care Control | Symptom Control | Improved Symptom Control (score increased >/=5 points from baseline) | 158 Participants |
| Usual Care Control | Symptom Control | Worsened Symptom Control (score decreased >/=5 points from baseline) | 170 Participants |
| Usual Care Control | Symptom Control | Non-responder for Symptom Control (score changed <5 points from baseline) | 215 Participants |