Non Steroidal Anti-inflammatory Drugs in the Prevention of Bone Pain Flares After Palliative Radiotherapy

Non-steroidal Anti-inflammatory Drugs in the Prevention of Bone Pain Flares After Palliative Radiotherapy: A Randomized Controlled Trial

Solid tumors have the tendency to spread to other organs in around 26% of cases, with many cases involving the bone causing severe bone destruction and pain that reduces patients' quality of life. Palliative radiation therapy is used as a standard of care to decrease cancer-related bone pain, as it has been proven to provide pain relief in many patients, either partially or totally, within only a few weeks. However, some patients experience worsening of bone pain especially within the first 10 days after radiation therapy, this is called bone pain flare, and its incidence is estimated to be around 40%. This pain flare tends to further reduce these patients' quality of life considering their main illness, which necessitates its prevention or alleviation.

Non-Steroidal Anti-inflammatory Drugs (NSAIDs) which are a key component of the World Health Organization (WHO) analgesic options used to alleviate cancer pain have not had a good share of published trials in the prevention of bone pain flares.

In this light the investigators aim to conduct a double-blinded, placebo-controlled randomized controlled trial to investigate the effectiveness of NSAIDs, specifically Proxen, in preventing bone pain flares after palliative radiotherapy, and as a secondary endpoint they will compare the quality of life and side effects experienced by patients in either group.

Study Overview

• Status: Not yet recruiting
• Conditions: Bone Metastasis; Bone Pain Flare
• Intervention / Treatment: Drug: Naproxen (Proxen S); Drug: Esomeprazole 20mg once daily; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 385
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Lara Hilal, MD; Phone Number: +96171233673; Email: lh54@aub.edu.lb
• Study Contact Backup: Name: Zeinab Dandash, MD; Phone Number: +96170214930; Email: zd27@aub.edu.lb

Study Locations

• Lebanon
  • Beirut, Lebanon, 1107 - 2020
    • American University of Beirut Medical Center
    • Contact: Lara Hilal, MD; Phone Number: +96171233673; Email: lh54@aub.edu.lb
    • Contact: Zeinab Dandash, MD; Phone Number: +96170214930; Email: zd27@aub.edu.lb

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age 18 years or older
• Primary Solid tumor (Any type of solid tumor)
• Painful bone metastases which are otherwise uncomplicated (no fracture and no neurologic symptoms due to nerve impingement or compression)
• Baseline pain score on a numeric rating scale (0-10) of at least 2
• Stable dose and schedule of narcotic medications prescribed

Exclusion Criteria:

• Hematologic malignancy
• Previously irradiated bone
• Current use of steroids
• Current use of NSAIDs which cannot be stopped before randomization
• Contraindications for NSAIDs (hypersensitivity, PUD, prior GI bleed, CKD, HTN, HF, AERD/asthma)
• Contraindications for PPIs

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: NSAID arm; People in this arm will receive the NSAID naproxen for 5 days, starting from the day they first receive palliative radiotherapy, they will take it as an initial dose of 500mg then as 250mg every 8 hours for a total of 5 days.	Drug: Naproxen (Proxen S); Naproxen will be given for 5 days starting from the day subjects first receive palliative radiotherapy, it will be taken as an initial dose of 500mg then as 250mg every 8 hours for a total of 5 days.; Other Names: NSAIDs; Drug: Esomeprazole 20mg once daily; Esomeprazole will be given to all subjects as 20mg once daily starting from the day they start palliative radiotherapy and for a total of 5 days.; Other Names: Nexium; PPI
Placebo Comparator: Placebo arm; People in this arm will receive placebo pills for 5 days, starting from the day they first receive palliative radiotherapy, they will take a placebo pill every 8 hours for a total of 5 days.	Drug: Esomeprazole 20mg once daily; Esomeprazole will be given to all subjects as 20mg once daily starting from the day they start palliative radiotherapy and for a total of 5 days.; Other Names: Nexium; PPI; Drug: Placebo; Placebo will be given for 5 days starting from the day subjects first receive palliative radiotherapy, it will be given every 8 hours for a total of 5 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of a pain flare within the first 10 days after palliative radiation therapy	Subjects will be monitored for the occurrence of a pain flare during the first 10 days after the start of their palliative radiotherapy through daily phone calls by the research fellow who will ask the necessary questions to fill out the Brief Pain Inventory questionnaire and compare baseline pain scores to follow-up pain scores. This questionnaire has a minimum score of 0 and maximum score of 110, with higher scores indicating more pain. A pain flare will be considered positive if there is: Two-point increase from baseline on a pain scale from 0-10 with no increase in analgesic medication intake OR; At least 25% increase in the intake of analgesic (daily oral morphine) with no decrease in pain scores on a pain scale	From enrollment till 10 days after the start of palliative radiotherapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in quality of life from start of palliative radiotherapy till one month after	Quality of life scores will be assessed through daily phone calls to the subjects performed by the research fellow who will ask the subjects the necessary questions to fill out the European Organization for Research and Treatment of Cancer Core Questionnaire (EORTC QLQ-BM22) and compare the baseline scores to the recent ones. This questionnaire has a minimum score of 22 and a maximum score of 88, with higher scores indicating greater distress and hence lower quality of life. The phone calls will be daily the first 10 days after start of palliative radiotherapy, and then weekly for a total of 30 days after the start of palliative radiotherapy.	From enrollment till 30 days after the start of palliative radiotherapy

Collaborators and Investigators

• Sponsor: American University of Beirut Medical Center
• Investigators: Principal Investigator: Lara Hilal, MD, AUBMC; Principal Investigator: Bassem Youssef, MD, AUBMC

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2025
• Primary Completion (Estimated): April 1, 2029
• Study Completion (Estimated): April 1, 2029

Study Registration Dates

• First Submitted: March 25, 2025
• First Submitted That Met QC Criteria: March 25, 2025
• First Posted (Actual): March 31, 2025

Study Record Updates

• Last Update Posted (Actual): April 4, 2025
• Last Update Submitted That Met QC Criteria: April 1, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Neoplasm Metastasis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Peripheral Nervous System Agents; Gastrointestinal Agents; Enzyme Inhibitors; Gout Suppressants; Antirheumatic Agents; Sensory System Agents; Analgesics, Non-Narcotic; Analgesics; Anti-Inflammatory Agents, Non-Steroidal; Cyclooxygenase Inhibitors; Anti-Ulcer Agents; Proton Pump Inhibitors; Naproxen; Esomeprazole
• Other Study ID Numbers: BIO-2024-0045

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No