Intrathecal Therapy Versus Standard Care for Severe Cancer Pain (CAREGIVER)

Intrathecal Drug Delivery Systems Versus Comprehensive Medical Management for Severe Cancer Pain: a Randomized Controlled Trial

Approximately 66% of patients with advanced cancer experience pain, which is often inadequately controlled and associated with a decline in health-related quality of life (HRQoL). Conventional pharmacologic management, ranging from simple analgesics to strong opioids, is frequently limited by insufficient efficacy and systemic side effects. Intrathecal drug delivery (IDD) offers targeted, continuous medication infusion directly into the intrathecal space, allowing lower systemic doses and potentially reducing side effects while maintaining effective analgesia. The CAREGIVER study is a randomized, controlled trial designed to evaluate whether patients with severe refractory cancer pain receiving IDD experience a difference in HRQoL compared to those receiving conventional medical management (CMM) with oral pain medications.

Study Overview

• Status: Recruiting
• Conditions: Refractory Cancer Pain; Intrathecal Drug Delivery; Conventional Medical Management
• Intervention / Treatment: Procedure: Intrathecal Drug Delivery; Drug: Comprehensive Medical Management

• Study Type: Interventional
• Enrollment (Estimated): 72
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Maarten Moens, MD PhD MBA; Phone Number: +3224775514; Email: stimulusresearchgroup@gmail.com
• Study Contact Backup: Name: Lisa Goudman, MSC, PhD; Phone Number: +32472412507; Email: lisa.goudman@vub.be

Study Locations

• Belgium
  • Jette, Belgium, 1090
    • Recruiting
    • UZ Brussel
    • Contact: Maarten Moens, MD PhD MBA; Phone Number: +3224775514; Email: stimulusresearchgroup@gmail.com
    • Sub-Investigator: Ulrike Van Hoey, MSc
    • Sub-Investigator: Britt Winnepenninckx, MSc
    • Sub-Investigator: Lisa Goudman, MSc, PhD
    • Sub-Investigator: Mark De Ridder, MD PhD
    • Principal Investigator: Maarten Moens, MD PhD MBA

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Adult patients (≥18 years) with severe cancer refractory pain (all types of cancer), who have been receiving treatment with oral/systemic opioids for at least 4 weeks, and are expected to remain on opioids for the entire duration of the study. More than one opioid rotation has to be done before defining pain refractoriness.
• Intrathecal therapy is recommended because of inefficacy or intolerance to strong systemic opioid treatment. Inefficacy is defined as mean daily visual analogue scale (VAS) pain intensity score at rest of ≥ 50 mm. Intolerance is defined as the occurrence of (S)AEs (even with dosage less than 200 mg/day of oral morphine equivalents) which prevents a further increase in the opioid dosage to obtain pain relief.
• Patients suitable for IDD and with the ability to comply with the medical protocol and visits.
• Survival prognosis of ≥ 6 months.

Exclusion Criteria:

• Patients with active, severe infection.
• Patients with known brain metastases.
• Patients with high risk of hemorrhaging.
• Patients with respiratory depression (for use of morphine).
• Patients with severe respiratory compromise; baseline oxygen SpO2 < 90%, chronic CO2 retention.
• Patients with severe cardiac disease or risk of cardiotoxicity (for use of bupivacaine).
• Patients with severe liver impairment or liver failure (for use of ropivacaine).
• Patients with allergies for medication or IDD hardware.
• Pregnant or lactating women.
• Women who plan to become pregnant within 1 month after the study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Intrathecal Drug Delivery	Procedure: Intrathecal Drug Delivery; Patients assigned to the IDD-group (intervention group) will undergo implantation of an IDD pump (Synchromed™, Medtronic). The device will be placed subcutaneously in the abdominal region and connected to a catheter delivering pain medication directly into the intrathecal space surrounding the spinal cord. At the time of implantation, the pump will be filled with medication, such as morphine, local anesthetics, or a combination thereof, and an initial daily dose will be selected. In the days following surgery, dose titration will be performed to establish the optimal balance between pain relief and tolerability. Following implantation, the most common postoperative procedure is the drug refill. This involves aseptic access to the pump reservoir, removal of any residual volume, and replenishment with a fresh dose of medication. Refill intervals will depend on the patient's daily dosage, ranging from monthly to once every 2-3 months.
Active Comparator: Comprehensive Medical Management	Drug: Comprehensive Medical Management; Participants randomized to the CMM-group will receive standard care.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Health-related quality of life	Health-related quality of life will be evaluated with the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30).	At baseline and 1, 2, 4, 6, 8, 10, and 12 months post-treatment initiation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient comfort	Patient comfort is evaluated with the General Comfort Questionnaire (GCQ), a self-reported instrument consisting of 48 items that reflect the physical, spiritual, environmental, and social dimension.	At baseline and 1, 2, 4, 6, and 12 months post-treatment initiation
Survival	The survival rate will be determined by recording the time from treatment initiation until death.	At baseline and 1, 2, 4, 6, and 12 months post-treatment initiation
Pain intensity	Pain intensity will be measured with the Visual Analogue Scale (ranging from 0 (no pain) to 100 (maximal pain)) in electronic format. Momentary data collection will be used to collect pain intensity scores for VAS (valid and reliable for pain experience), whereby pain intensity is measured for multiple times per day for 1 week to reveal patterns of transient or fluctuating symptoms in the environment and context of the patients' lives, without a recall bias.	At baseline and 1, 2, 4, 6, 8, 10, and 12 months post-treatment initiation
Perceived stress	Perceived stress will be assessed by using the 10-item Perceived Stress Scale.	At baseline and 1, 2, 4, 6, and 12 months post-treatment initiation
Anxiety	Patient anxiety will be provided through the State Trait Anxiety Inventory (STAI).	At baseline and 1, 2, 4, 6, and 12 months post-treatment initiation
Perceived Injustice	Using the Injustice Experience Questionnaire (IEQ), perceived injustice related to current health status will be assessed.	At baseline and 1, 2, 4, 6, and 12 months post-treatment initiation
Self-efficacy	The General Self-Efficacy (GSE) Scale is a 10-item self-report questionnaire used to assess perceived self-efficacy.	At baseline and 1, 2, 4, 6, and 12 months post-treatment initiation
Caregiver burden	To evaluate caregiver burden, the Zarit Burden Interview (ZBI) questionnaire will be completed. This 12-item self-report instrument assesses caregiver burden and is a shortened version of the original 22-item Zarit Burden Scale.	At baseline and 1, 2, 4, 6, and 12 months post-treatment initiation
Health expenditure	Expenditures related to in-hospital care will be extracted from hospital claims data. All other healthcare-related costs will be gathered through telephone interviews with patients, conducted each month after treatment initiation. During these calls, researchers will ask patients whether they have had any medical consultations, hospital admissions, AEs, changes in medication (such as daily morphine, MED, antidepressants,…), or incurred any additional healthcare costs.	monthly after treatment initiation until 12 months
Safety	Recording of (serious) adverse events.	Throughout the duration of the study, an average of 12 months.
Number of responders	Responder status will be determined based on pain scores, adverse events, and medication dose changes. Responders are defined as patients achieving a clinically meaningful reduction in pain intensity (≥30% from baseline) without intolerable adverse effects.	at 1, 2, 4, 6, and 12 months post-treatment initiation

Collaborators and Investigators

• Sponsor: Universitair Ziekenhuis Brussel

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): October 31, 2029
• Study Completion (Estimated): October 31, 2029

Study Registration Dates

• First Submitted: June 30, 2026
• First Submitted That Met QC Criteria: July 7, 2026
• First Posted (Actual): July 9, 2026

Study Record Updates

• Last Update Posted (Actual): July 9, 2026
• Last Update Submitted That Met QC Criteria: July 7, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Neuromodulation; Health-related quality of life; Refractory cancer pain; Intrathecal pumps; Intrathecal drug delivery
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Cancer Pain
• Other Study ID Numbers: 2025-522381-68-00

Drug and device information, study documents

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