The In4M Study: Integrating 4 Methods to Assess Physical Function in Cancer Patients

This is a prospective observational cohort study. Breast cancer and lymphoma patients planned to receive cytotoxic therapy will be recruited at Yale and Mayo Clinic. The Study Period is 9 months, during which enrolled patients will use their personal smartphone, computer, or other web-connected device to connect with the Hugo platform which will deliver PRO questionnaires, and sync to the wearable device in the study (Fitbit). The PerfO (6MWT) will be conducted twice in clinic during the study period. Structured information from the electronic health record (EHR) and patient portals will be collected and where needed, the EHR will be directly reviewed to record AEs, hospitalizations/emergency department visits and dose delay/reductions. Required in-person face to face visit is only at baseline for consent, enrollment and receipt of wearable device; patients can be followed remotely afterward (i.e. do not need to be treated at Mayo or Yale)

Study Overview

• Status: Completed
• Conditions: Quality of Life; Lymphoma; Cancer, Breast; Physical Function; Patient Empowerment; Patient Education
• Intervention / Treatment: Other: PRO Instruments assessment questionnaire; Other: Baseline Survey Clinician- reported (ClinRO) ECOG; Device: Fitbit; Other: Hugo Health ("Hugo"); Other: 6 Minute Walk Test (6MWT)

Detailed Description

The purpose of this prospective observational study is to collect and evaluate 4 different sources of physical functioning (PF) data over the course of systemic anti-cancer therapy in lymphoma and breast cancer patients: clinician-reported Performance Status (PS), Patient Reported Outcomes (PROs), a Performance Outcome (PerfO) and patient wearable device data.

Aim 1: To measure PF using 4 distinct modalities (ClinRo, PRO, PerfO and wearable device data) on Hugo platform

• Characterize assessment challenges by comparing levels of missing data and reasons for missingness across the PF modalities
• Report on trajectories of function as ascertained by the 4 PF modalities

Aim 2: To explore associations between various sources of physical function data and determine change thresholds

• To identify measurement characteristics of the PF modalities including sensitivity to change and identification of meaningful change thresholds
• Compare change over time in data within and between the PF modalities
• Explore associations between changes in the various PF modalities and subsequent patient-reported adverse events (AEs), acute care use (unplanned hospitalizations or emergency department visits), other patient-reported domains of Health Related Quality of Life (HRQOL), and dose delay/reduction

Aim 3: To assess patient acceptability and experience using the different PF assessment modalities

• Administer an exit questionnaire to understand burden and usability of electronic PROs and wearable device data collection from the patient perspective

The allocation for patient recruitment is 18 months, with 9 months for follow up for each patient. The proposed overall project timeline is 3.5 years/39 months. A total of 200 patients will be enrolled at Yale Cancer Center and the Mayo Clinic, as outlined below. Data will be cleaned, reviewed, and analyzed as it is received from the Hugo platform on a rolling basis. Data analysis will be conducted at Mayo Clinic and Yale. Only de-identified data will be provided to the FDA.

• Study Type: Observational
• Enrollment (Actual): 208

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Yale Cancer Center
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Two hundred patients will be recruited from two main sites: Yale and Mayo Clinic Rochester. Patient sampling will be stratified by site enrolled and cancer type. The investigator will seek to optimize diversity of the patient sample. Race/ethnicity will be determined by participant self-report, offering the opportunity for participants to select multiple races. Participants who self-define as part of a racial or ethnic minority and as white will be classified by their non-white race/ethnicity for purposes of counting enrollment quotas. The project team (including representatives from the FDA) will evaluate the enrollment throughout the study both in terms of counts as well as demographic mix. For the purposes of this study, specific goals or quotas are not being set.

Description

Inclusion Criteria:

1. Age 18 and over;
2. English- or Spanish-speaking;
3. Pregnant and non-pregnant patients are eligible for participation in this study
4. Eligible cancer type and planned intravenous cytotoxic chemotherapy regimen (defined as including 1 or more cytotoxic agents)
5. ECOG Performance Score of < 3

6. Breast cancer patients

   a) Patients with any stage breast cancer for whom a new intravenous cytotoxic chemotherapy regimen is planned within the next 8 weeks (patients with local/regional/distant recurrences are allowed; patients with concurrent/prior/future immunotherapy/radiotherapy, targeted therapy, and endocrine therapy for breast cancer are allowed)

7. Lymphoma patients

   a) Lymphoma patients of any histology, stage or line of treatment planned to receive a new intravenous cytotoxic containing chemotherapy regimen (patients planned to receive radiation, maintenance chemotherapy, consolidation stem cell transplant or chimeric antigen receptor T (CAR-T) cell therapy are allowed)

8. If patients are receiving the above standard therapies as part of a clinical trial which may include a novel agent or combination, they are also eligible for the present study if the therapeutic protocol permits enrollment in both studies
9. Willing and able to give consent and participate in study
10. Able to access a mobile device (smartphone or tablet) or computer with web access every day to complete study surveys; able to regularly upload data from the Fitbit to a device in a way that it can be transferred to Hugo
11. Willing and able to perform an in-clinic 6-minute walk test (gait aides are permitted if regularly used by the patient). If a patient is recruited remotely outside of Mayo Clinic Rochester or Yale Smilow Cancer Center New Haven, 6-minute walk test may be omitted.
12. Willing to use the health data sharing platform Potential subjects who do not meet all of the enrollment criteria will not be enrolled. Any deviations from these criteria must be reported in accordance with IRB Policies and Procedures.

Exclusion Criteria

1. Prior intravenous cytotoxic chemotherapy within 3 weeks prior to study enrollment

2. Excluded regimens (due to length of hospitalization required for chemotherapy administration):

   1. R-CODOX-M/IVAC,
   2. DA-R-EPOCH (inpatient)

3. Excluded histology (due to length of hospitalization and inpatient predominant treatment for required chemotherapy): primary central nervous system lymphoma

   a) Other regimens with an anticipated high duration of inpatient care time, at PI discretion

4. Lack of access to a mobile device (smartphone or tablet) or computer with web access
5. Unable or unwilling to connect Fitbit to device
6. Unable or unwilling to use the health data sharing platform
7. Unable to give consent and be enrolled

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

evaluating sources of physical function (PF); evaluate 4 distinct modalities of sources of PF (PRO, ClinRo, PerfO and wearable device data) on Hugo Health platform in breast cancer and lymphoma patients undergoing cytotoxic chemotherapy.

Other: PRO Instruments assessment questionnaire; Patient Reported Outcome (PRO) questionnaire consisting of: PRO-CTCAE (approximately 11 questions plus free text); Patient-Reported Outcomes Measurement Information System (PROMIS) physical function short form (version 8c) (8 questions); PRO ECOG question (1 question); EORTC Quality of Life questionnaire (QLQ)-F17 questions (17 questions); Functional Assessment of Cancer Therapy-General version, rated on a 5-point Likert scale, (FACT-GP5) (single item global side effect bother question) (1 question); The Patient Global Impression (PGI)-C and PGI-S items (anchors for physical function) (2 questions); Other: Baseline Survey Clinician- reported (ClinRO) ECOG; Baseline Survey completed prior to initiation of chemotherapy; Device: Fitbit; wearable device; Other: Hugo Health ("Hugo"); an electronic platform that aggregates real world EHR data with patient's wearable and PRO data; Other: 6 Minute Walk Test (6MWT); A comprehensive performance measure of exercise capacity, encompassing components of mobility, endurance, and functional capacity measure (PerfO)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To measure Physical Function using Clinician Reported Outcomes (ClinRo) at baseline.	ClinRo score at baseline using the Eastern Cooperative Oncology Group (ECOG) performance scale. Possible scores range from 0 to 5. The lower the score the better the performance.	baseline
Change in Patient Reported Outcomes Questionnaire: PRO-CTCAE	PRO-CTCAE is a patient-reported outcome (PRO) measurement system of 11 questions plus free text developed to evaluate symptomatic toxicity in patients on cancer clinical trials. Outcome reported as a count of adverse events.	baseline, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 8, Month 3, Month 4, Month 5, Month 6, Month 7, Month 8, and Month 9.
Change in Patient Reported Outcomes Questionnaire: PROMIS	Patient-Reported Outcomes Measurement Information System (PROMIS), version 8c, is a patient reported survey which evaluates a patient physical function before and during treatment. It consists of 8 questions each scored from 5 (without any difficulty) to 1 (Unable to do).	baseline, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 8, Month 3, Month 4, Month 5, Month 6, Month 7, Month 8, and Month 9.
Change in Patient Reported Outcomes Questionnaire: PRO ECOG	PRO ECOG is 1 question where patients describe their activity in the past month. Score ranges from 0 (normal with no limitations) to 3 (unable to perform activities, very limited).	baseline, Week 2, Week 4, Week 6, Week 8, Month 3, Month 4, Month 5, Month 6, Month 7, Month 8, and Month 9.
Change in Patient Reported Outcomes Questionnaire: EORTC Quality of Life (QLQ)-F17	EORTC Quality of Life questionnaire (QLQ)-F17 is a 17 question survey. The first 15 questions assess the patient's physical function and are scored from 1 (Not at all) to 4 (Very much). The final 2 questions asses the patient overall health and overall quality of life. Scoring ranges from 1 (very poor health/quality of life) to 7 (excellent health/quality of life).	baseline, Week 2, Week 4, Week 6, Week 8, Month 3, Month 4, Month 5, Month 6, Month 7, Month 8, and Month 9.
Change in Patient Reported Outcomes Questionnaire: FACT-GP5	Functional Assessment of Cancer Therapy-General version (FACT-GP5) is a single question in which patients report their bother by side effects of treatment. Scores range from 0 (not at all bothered by side effect) to 4 (very much bothered by side effects).	baseline, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 8, Month 3, Month 4, Month 5, Month 6, Month 7, Month 8, and Month 9.
Change in Patient Reported Outcomes Questionnaire: Patient Global Impression-Change (PGI-C) and Patient Global Impression-Severity (PGI-S)	A two question survey. Question one, PGI-S, describes severity of symptoms of on a scale from 1 (normal severity) to 4 (severe symptoms). Question two, PGI-C, patients report how their physical function has changed from baseline on a scale from 1 (very much improved) to 7 (very much worse).	baseline, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 8, Month 3, Month 4, Month 5, Month 6, Month 7, Month 8, and Month 9.
Change in Physical Function using Performance Outcome 6-Minute Walk Test	Performance Outcome measured using a 6-minute walk test. The outcome is distance in meters traveled by the patient in a 6 minute time period at baseline and 3 months to evaluate patient performance before and after chemotherapy.	baseline and 3 months
Steps Data From Wearable Device	Count of total daily steps and maximum cadence (steps/minute) with activity data collected using a Fitbit at baseline (7 days prior to the start of chemotherapy) continually until Month 9.	baseline through month 9
Heart Rate Data From Wearable Device	Resting heart rate (beats/minute) and heart rate during moderate to vigorous physical activity (MVPA) data collected using a Fitbit at baseline (7 days prior to the start of chemotherapy) continually until Month 9.	baseline through month 9
Patient Activity Data From Wearable Device	Daily duration of MVPA (in minutes), count of ≥10-minute bouts of MVPA, daily duration of sedentary time (in minutes), and count of ≥ 10-minutes bouts of sedentary time (in minutes) data collected using a Fitbit at baseline (7 days prior to the start of chemotherapy) continually until Month 9.	baseline through month 9

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: Food and Drug Administration (FDA)
• Investigators: Principal Investigator: Cary Gross, MD, Yale University

Study record dates

Study Major Dates

• Study Start (Actual): January 27, 2022
• Primary Completion (Actual): August 22, 2024
• Study Completion (Actual): October 24, 2024

Study Registration Dates

• First Submitted: January 13, 2022
• First Submitted That Met QC Criteria: January 27, 2022
• First Posted (Actual): January 28, 2022

Study Record Updates

• Last Update Posted (Estimated): November 7, 2024
• Last Update Submitted That Met QC Criteria: November 6, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: 2000031319; 2U01FD005938-03 (U.S. FDA Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No