Corticosteroids for Cancer Pain

Study hypothesis: corticosteroids are effective for pain in cancer patients. We will perform a double-blind, randomized, placebo-controlled multicentre trial evaluating the effect of Methylprednisolone 16 mg twice daily in cancer patients with pain (average pain last 24 hrs NRS > 4 (Numerical rating scale, 0 No pain, 10 worst pain).

Study Overview

• Status: Completed
• Conditions: Pain; Cancer
• Intervention / Treatment: Drug: Methylprednisolone; Drug: Placebo

Detailed Description

Patients are required to use strong opioids before entering the study. Weak opioids are allowed if patients have short acting strong opioids as rescue-medication. The scheduled opioids shall be stable last 48 hours before entering the study and will be kept stable during the study period. Patients may use as much short acting rescue-medication as they require. No other analgesic medication should be started during the study period.

The study is a multicentre trial. Patients will be randomized according to 1. study centre (No 1-5) and 2. pain mechanism: skeletal metastases (yes/no).

Patients are evaluated Day 0 and Day 7 by palliative care physician. Patients will be contacted by phone Day 1-6 and will fill in questionnaire regarding symptoms and analgesic usage. Patients will be contacted Day 14 and 21 to fill in questionnaires regarding symptoms, quality of life and side effects.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 3

Contacts and Locations

Study Locations

• Norway
  • Bergen, Norway, 5009
    • Haraldsplass Diakonale sykehus
  • Drammen, Norway, 3004
    • Sykehuset Buskerud HF
  • Kristiansand, Norway, 4606
    • Sørlandet Sykehus HF
  • Oslo, Norway, 0407
    • Oslo universitetssykehus, Ullevål
  • Skien, Norway, 3712
    • Sykehuset Telemark HF
  • Trondheim, Norway, 7006
    • St Olavs Hospital HF

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Verified malignant disease
• Receiving a scheduled strong or weak opioid
• Insufficient pain control: Average pain last 24 h: ≥ 4 (NRS 0-10)
• Given informed consent according to the ethical guidelines
• Able to complete planned assessment schedules
• ≥ 18 years of age
• Life expectancy > 1 month

Exclusion Criteria:

• Excruciating pain (average pain ≥ 8) (These patients should be considered as emergency patients. Patients may be eligible for the study after stabilization)
• Dose adjustment in scheduled opioid medication last 48 hours
• Concurrent medication with NSAIDs (Patients are eligible for the study one week after NSAIDs are discontinued)
• Receiving radiotherapy within 4 weeks before entering the study or planned within the study period
• Started systemic treatment (chemotherapy, hormone therapy or bisphosphonates) within 4 weeks before entering the study Patients who have received chemotherapy for more than 4 weeks are eligible for the study if it is more than 7 days since receiving the last dose and they are not having the next dose within the study period
• Manifest spinal cord compression or in need of bone surgery
• Severe cognitive impairment
• Previously on steroids during the last 4 weeks
• Diabetes mellitus
• Known peptic ulcer disease
• Systemic fungal disease, patients vaccinated with viable viruses, and patients with known allergies to the study medication (MethylPrednisolone)
• Female patients who are pregnant or lactating.
• Women of reproductive potential not willing or unable to employ an effective method of contraception (be sterilized, using IUD or oral contraception)
• Patients using following medication: cyclosporin, erythromycin, phenobarbital, phenytoin, carbamazepin, ketoconazole, methotrexate, ciclofosfamide, rifampicin, aprepitant and diltiazem.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo capsules twice daily	Drug: Placebo; Custom made capsules, Lactose, administered twice daily, intervention period 7 days
Experimental: Methylprednisolone; Methylprednisolone 16 mg twice daily	Drug: Methylprednisolone; Custom made capsules, Methylprednisolone 16 mg twice daily, intervention period 7 days.; Other Names: Medrol (TM)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pain intensity at Day 7	change of pain intensity at Day 7, measured by "average pain for the last 24 hours" (NRS 0-10).	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
fatigue	change of fatigue measured by EORTC QLQ30 and ESAS	7 days
appetite	change of appetite measured by EORTC QLQ30 and ESAS	7 days
Overall effect satisfaction	Overall effect measured by a global satisfaction-question ("How is your overall benefit from the medication?" NRS: 0= No important benefit 10=very important benefit).	7 days
sleep quality	change of sleep quality measured by Pittsburgh Sleep Quality Index	7 days
analgesic usage	change of analgesic usage measured by morphine equivalents.	7 days
Pain now and average pain last 24 hrs	Pain now and average pain last 24 hours measured by daily NRS (Numeric rating scale)(ESAS)	7 days

Collaborators and Investigators

• Sponsor: Norwegian University of Science and Technology
• Investigators: Study Director: Stein Kaasa, MD PhD prof, Norwegian University of Science and Technology

Publications and helpful links

General Publications

• Paulsen O, Klepstad P, Rosland JH, Aass N, Albert E, Fayers P, Kaasa S. Efficacy of methylprednisolone on pain, fatigue, and appetite loss in patients with advanced cancer using opioids: a randomized, placebo-controlled, double-blind trial. J Clin Oncol. 2014 Oct 10;32(29):3221-8. doi: 10.1200/JCO.2013.54.3926. Epub 2014 Jul 7.
• Jakobsen G, Engstrom M, Hjermstad MJ, Rosland JH, Aass N, Albert E, Kaasa S, Fayers P, Klepstad P, Paulsen O. The short-term impact of methylprednisolone on patient-reported sleep in patients with advanced cancer in a randomized, placebo-controlled, double-blind trial. Support Care Cancer. 2021 Apr;29(4):2047-2055. doi: 10.1007/s00520-020-05693-6. Epub 2020 Aug 27.

Study record dates

Study Major Dates

• Study Start: April 1, 2008
• Primary Completion (Actual): February 1, 2012
• Study Completion (Actual): February 1, 2012

Study Registration Dates

• First Submitted: May 8, 2008
• First Submitted That Met QC Criteria: May 12, 2008
• First Posted (Estimate): May 13, 2008

Study Record Updates

• Last Update Posted (Actual): September 1, 2020
• Last Update Submitted That Met QC Criteria: August 30, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: Cancer; pain; supportive care; palliative; corticosteroids; Cancer patients with pain
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Cancer Pain; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Neuroprotective Agents; Protective Agents; Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate
• Other Study ID Numbers: OPI 07-005; 2007-005617-19 (EudraCT Number)