Condition category
Cancer
Date applied
18/03/2005
Date assigned
29/03/2005
Last edited
07/12/2012
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Cancer related-pain continues to be a major problem for eight out of ten cancer patients. For many years the main treatment for cancer-related pain has been morphine. Morphine is a strong painkiller which belongs to a family of drugs called opioids. About one in four people do not respond well to morphine either because of severe side effects or not enough pain relief. If this happens, switching to another strong opioid painkiller, such as oxycodone, appears to be helpful.
The main aim of the study was to find out which strong opioid is best to use first-line in the treatment of moderate to severe cancer-related pain, morphine or oxycodone. Another aim was to find out whether switching from one strong opioid to another when the first is not working does indeed improve pain relief. The study also investigated whether there was anything that could predict which strong painkiller would be best for a particular person. Part of this was done by looking for differences in DNA, the genetic code that is unique to each person, which could be linked to certain responses.

Who can participate?
The study included patients who were over 18 years of age, had a diagnosis of cancer and had pain that was not controlled on a weak opioid painkiller such as codeine.

What did the study involve?
Two hundred participants with cancer-related pain were recruited to the study. Participants were randomised to receive either morphine or oxycodone by mouth. Neither the participant nor the doctor could choose which strong opioid they would be given. Participants were monitored daily until good pain control was achieved. If the participants did not experience good pain relief despite increasing the dose or reported bad side effects they were switched to the alternative strong opioid painkiller. Questionnaires on pain and side effects were collected together with information about other medications, and blood and urine samples at the different time points. The study lasted one year in total. The time-points were: at the beginning, when a good response was achieved, when a switch to the other opioid painkiller was necessary, if the dose required for good pain control trebled in follow-up period and at the end of the study.

What were the possible benefits and risks of participating?
This study was designed to find out which painkiller is best to use first-line for cancer-related pain in order to get symptoms under control as safely and as quickly as possible. Ultimately we would like to be able to predict a person’s response to each painkiller before they start in order to tailor care to the individual.
The two opioid painkillers used in the study are commonly used in the treatment of cancer-related pain, so doctors and nurses are very familiar with their use. The study participants were closely followed-up and side effects were reported. Common side effects include constipation, nausea, vomiting and drowsiness. The number of times the participants were asked to come to the hospital was kept to a minimum.

Where was the study run from?
The Royal Marsden Hospital

When is the study starting and how long is it expected to run for?
The study started in 2006 and finished recruiting in 2011.

Who is funding the study?
Palliative Care Research Fund, Royal Marsden Hospital and St Joseph’s Hospital. The study also received an unrestricted educational grant from NAPP Pharmaceutical Group.

Who is the main contact?
Dr Julia Riley
julia.riley@rmh.nhs.uk

Trial website

Contact information

Type

Scientific

Primary contact

Dr Julia Riley

ORCID ID

Contact details

The Royal Marsden Hospital
Fulham Road
London
SW3 6JJ
United Kingdom

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N0258161811

Study information

Scientific title

A Prospective Randomized Controlled Trial of Morphine versus Oxycodone for Cancer Pain: Genetic Determinants of Response to Opioids

Acronym

Study hypothesis

1. To compare the response rates of morphine and oxycodone when used as first line strong opioids in moderate to severe cancer pain.
2.1 To compare the toxicity profiles of morphine and oxycodone and identify which factors
predict that need to switch from one opioid to the other.
2.2 To compare clinical, laboratory, genomic, proteomic and metabonomic parameters of the study populations in order to design a model that predicts response and non-response to morphine and oxycodone.

Please note, as of 23/06/2011 various updates have been made to this trial. These can be found under this date of update in the relvevant fields below.
The anticipated start date has been updated from 01/05/2005 to 01/05/2006. The anticipated end date has been extended from 01/11/2007 to 31/08/2011.

Ethics approval

London-Surrey Borders Research Ethics Committee on 07/07/2005 (ref: 05/Q0806/58)

Study design

Randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Quality of life

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Moderate to severe cancer pain

Intervention

Randomisation to receive oral morphine or oral oxycodone as first line Step 3 analgesics in moderate to severe cancer pain, and switch to alternative arm of study if lack of response to drug of initial study treatment arm.

Intervention type

Drug

Phase

Not Specified

Drug names

Morphine versus Oxycodone

Primary outcome measures

Difference in response rate to morphine versus oxycodone.

Secondary outcome measures

Differences in levels of toxicity and differences in pre-specified clinical, laboratory, genetic, immunological and proteomic determinants between the two study groups.

Overall trial start date

01/05/2005

Overall trial end date

31/08/2011

Reason abandoned

Eligibility

Participant inclusion criteria

1. Patients must have a clinical or histological diagnosis of cancer
2. Patients whose pain is not controlled on Step 2 (weak opioid) analgesics (as defined by the WHO analgesic ladder) who clinically require a strong opioid
3. Patients must be over 18 years of age
4. Patients must be able to give written informed consent
5. Patients must be willing to undergo genetic screening

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

200

Participant exclusion criteria

Current exclusion criteria as of 23/06/2011:
1. Patients with renal failure (1.5x ULN). These patients should be treated with alfentanil as per Palliative Care Clinical Guidelines
2. Patients must not currently be taking regular strong opioids
3. Patients requiring parenteral administration of opioids
4. Patients with predominantly incident pain
5. Patients with a clearly defined history of intolerance to morphine or oxycodone
6. Patients who are pregnant

Previous exclusion criteria:

1. Patients with renal failure (1.5 x upper limit of normal [ULN]). These patients should be treated with alfentanil as per palliative care guidelines.
2. Patients must not have been taking regular Step 3 analgesics in the last month
3. Patients requiring parenteral administration of opioids
4. Patients with predominantly neuropathic pain
5. Patients with predominantly incident pain
6. Patients with a clearly defined history of intolerance to morphine or oxycodone

Recruitment start date

01/05/2005

Recruitment end date

31/08/2011

Locations

Countries of recruitment

United Kingdom

Trial participating centre

The Royal Marsden Hospital
London
SW3 6JJ
United Kingdom

Sponsor information

Organisation

The Royal Marsden NHS Foundation Trust (UK)

Sponsor details

Fulham Road
London
SW3 6JJ
United Kingdom

Sponsor type

Research organisation

Website

Funders

Funder type

Research organisation

Funder name

The Palliative Care Research Fund

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Royal Marsden Hospital and

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

St Joseph’s Hospital.

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

NAPP Pharmaceutical Group (unrestricted educational grant)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes