MultidISciplinary Care paThway tailoRed on frAilty in Cancer Patients Referred to Outpatient paLliative Care (MISTRAL)

The goal of this clinical trial is to learn whether a structured, Patient-Reported Outcome Measures (PROMs)-tailored palliative care pathway improves clinical outcomes and care experience in adults with advanced cancer referred to outpatient palliative care.

Patients with advanced cancer often experience multiple symptoms and complex needs. Standard outpatient palliative care is usually guided by clinical judgment on patient-reported questionnaires. In this study, researchers aim to test whether a more structured approach, based on predefined cut-offs from PROMs, can improve symptom control, satisfaction with care, and use of healthcare resources. The main questions the study aims to answer are:

Does a structured, PROM-driven palliative care pathway reduce symptom burden and psychological distress compared with usual care? And through this, to improve patients' and caregivers' satisfaction with care or reduce emergency room visits, hospital admissions, healthcare costs, and aggressive treatments near the end of life?

Researchers will compare two groups:

Control group: Participants will receive standard outpatient palliative care. PROMs are collected as usual, but without predefined cut-offs or structured intervention checklists.

Experimental group: Participants will receive a structured palliative care pathway tailored to symptoms/needs identified at baseline using PROM cut-offs. Specific multidisciplinary interventions are activated according to identified needs.

Study Overview

• Status: Recruiting
• Conditions: Cancer; Frailty; Palliative Care; Outpatient; Palliative Care, Health Services; Patient Reported Outcome Measurements; Patient Reported Outcome (PRO)
• Intervention / Treatment: Other: Structured Palliative Care; Other: Classical Palliative Care

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Giacomo Massa, Dr; Phone Number: +39 0223903279/3272; Email: giacomo.massa@istitutotumori.mi.it

Study Locations

• Italy
  • Lombardy
    • Milan, Lombardy, Italy, 20133
      • Recruiting
      • IRCCS Istituto Nazionale dei Tumori, Via Venezian n1
      • Contact: Giacomo Massa, Dr; Phone Number: +39 0223903279/3272; Email: giacomo.massa@istitutotumori.mi.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• diagnosis of advanced/metastatic cancer
• age > 18
• Eastern Cooperative Oncology Group (ECOG) performance status ≥2
• prognostic clinical prediction >1 month.

Exclusion Criteria:

• Serious medical or psychiatric illness that can interfere with informed consent and participation in this clinical study
• any condition that is unstable or could jeopardize the safety of the patient and their compliance in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Structured interventions tailored to PROMs cut-off; • Experimental group, which will follow a structured palliative care pathway (specific intervention defined in the protocol) based on the frailties identified at baseline PROMs (defined by cut-off).	Other: Structured Palliative Care; Symptoms/needs domains are defined according to protocol-specified cut-offs, followed by the activation of a tailored intervention based on structured checklists targeting the reported symptoms/needs.
Active Comparator: Classic Palliative Car interventions; • Control group, which will undergo standard unstructured palliative care (based on PROMs as usual, but without cut-off or interventions' checklists)	Other: Classical Palliative Care; Multidisciplinary palliative care interventions are delivered according to usual clinical practice, without activation based on predefined cut-offs or structured algorithms.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in overall symptom burden assessed by the ESAS.	- Mean change in symptom burden from baseline to 1 month after initiation of palliative care, measured using the Edmonton Symptom Assessment System (ESAS) total score (range 0-90, higher scores indicating greater symptom burden). The analysis will compare the change in ESAS total score between the two randomized groups.	1, 3 months
Change in psychological distress assessed by the Distress Thermometer (DT).	Mean change in psychological distress from baseline to 1 month after initiation of palliative care, measured using the Distress Thermometer (DT) (range 0-10, higher scores indicating greater distress). The analysis will compare the change in DT score between the two randomized groups.	1, 3 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patients' satisfaction with care	The higher satisfaction with care after a structured intervention based on baseline PROMs. Endpoints: improvement in satisfaction with care measured by FAMCARE (Family Satisfaction with Advanced Cancer Care)-P13. This self-administered questionnaire utilizes a 5-point Likert scale (from 1 = "very dissatisfied" to 5 = "very satisfied"), range 0-65, where the total score is directly proportional to satisfaction levels (higher scores indicate more satisfaction).	1, 3 months
Healthcare resource utilization	the differences between the experimental and control groups concerning the number of total visits, emergency room admissions, and urgent hospital admissions during the follow-up	3, 6 months
Differeces in End of Life (EoL) care aggressiveness criteria	the differences between the experimental and control groups concerning the number of emergency room admissions, oncological therapy (radiotherapy, surgery, systemic), and hospitalizations occurring within 30 days of death (end of life, EoL).	3, 6 months
Caregivers' satisfaction with care	The higher satisfaction with care after a structured intervention based on baseline PROMs. Endpoints: improvement in satisfaction with care, measured by FAMCARE (Family Satisfaction with Advanced Cancer Care). This self-administered questionnaire utilizes a 5-point Likert scale (from 1 = "very dissatisfied" to 5 = "very satisfied"), range 0-85, where the total score is directly proportional to satisfaction levels (higher scores indicate more satisfaction).	1, 3 months

Collaborators and Investigators

• Sponsor: Augusto Caraceni

Study record dates

Study Major Dates

• Study Start (Actual): November 2, 2025
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): February 28, 2027

Study Registration Dates

• First Submitted: March 5, 2026
• First Submitted That Met QC Criteria: March 9, 2026
• First Posted (Actual): March 13, 2026

Study Record Updates

• Last Update Posted (Actual): March 13, 2026
• Last Update Submitted That Met QC Criteria: March 9, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Outpatient; Advanced cancer; Palliative Care; Frailty; Patient Reported Outcome Measurements (PROMs); Palliative Care intervention
• Additional Relevant MeSH Terms: Pathologic Processes; Pathological Conditions, Signs and Symptoms; Frailty; Neoplasms
• Other Study ID Numbers: INT 101/25

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

De-identified IPD underlying published results, together with the study protocol, statistical analysis plan, and data dictionary, will be shared in line with the FAIR principles and the "as open as possible, as closed as necessary" approach of Horizon Europe. Data management will follow a predefined Data Management Plan and comply with Regulation (EU) 2016/679 (GDPR) and GCP standards.

Data will be available from 6 months after publication for at least 5 years through controlled access, subject to a scientifically sound proposal, steering committee approval, and a Data Access Agreement.

• IPD Sharing Time Frame: The study protocol, statistical analysis plan, and informed consent form template will be made available upon reasonable request following study registration and may be shared prior to publication. De-identified individual participant data underlying the published results, together with a data dictionary, will be made available beginning 6 months after publication of the primary results and for at least 5 years thereafter. Data will be shared through a controlled access process, subject to submission of a methodologically sound proposal, approval by the study steering committee, and execution of a Data Access Agreement, in compliance with GDPR and GCP standards.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

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