Advanced CancerPhase 3NCT00634010
Morphine Versus Methadone As First Line Strong Opioid for Cancer Pain
A Phase 3 study testing Morphine and Methadone in people with Advanced Cancer and Solid Tumors, run by M.D. Anderson Cancer Center at 3 sites in United States.
Trial summary
Primary Aims: To determine whether methadone used as first line strong opioid is superior to morphine as evidenced by reduced pain over a 12-week treatment period in patients with advanced cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Cancer, Solid Tumors
- What is being tested?
- Morphine and Methadone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 3 sitesUnited States
- Study dates
- Feb 2008to Jan 2015
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient has pain caused by advanced cancer (local recurrence or metastatic disease)
- Patient reporting average pain score for the last 24 hours is >/= 4 on a numerical scale from 0 to 10 (0= no pain, 10=the worst possible pain).
- Patient is receiving mild opioids (e.g. propoxyphene, codeine, tramadol, hydrocodone), mixed agonist/antagonist (e.g. buprenorphine) or no opioids.
- Patient requires initiation of strong opioid for cancer pain.
- Patient has the ability to receive morphine or methadone orally.
- Patient has no known allergy or severe toxicity to morphine or morphine-like drugs (e.g. hydromorphone, oxycodone, oxymorphone, codeine, hydrocodone, levorphanol), or methadone or methadone-like drug (e.g. propoxyphene).
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- Patient has normal cognition defined as normal state of arousal and absence of obvious clinical findings of confusion, memory or concentration deficit.
- Patient has normal renal function (creatinine and blood urea nitrogen (BUN) within normal limits) </= 4 weeks of study entry.
- Patient's performance status (ECOG) is 3 or less.
- Patient is willing to sign written informed consent.
- Patient is 18 years of age or older.
- Patient is able to return to clinic for evaluation by physician day 8 , 15 , 29, 57 and 85 ( +/- 3 days) during study period.
Who cannot join
- Patient has concurrent strong opioid for cancer pain, such as morphine, hydromorphone, oxycodone, meperidine, fentanyl, oral transmucosal fentanyl citrate (OTFC), sufentanil, methadone, levorphanol, transdermal fentanyl.
- Patient is receiving radiation therapy for pain control.
- Patient is receiving drugs that interacting with methadone, such as (delavirdine, fluconazole, fluvoxamine, bravavir, amprenavir, efavirenz, lopinavir, nelfinavir, nevirapine, carbamazepine, dexamethasone (Patients receiving short term chemotherapy-related doses are permitted) , phenytoin, rifampin, or grapefruit,).
- Patients are determined incapable of completing the evaluation forms.
- Severe hypotension, acute or severe asthma, paralytic ileus, gastrointestinal obstruction, severe respiratory depression.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
LBJ General Hospital
Houston, Texas, 77030
The Michael E. DeBakey V.A. Medical Center
Houston, Texas, 77030
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
About this study
Primary Aims:
- To determine whether methadone used as first line strong opioid is superior to morphine as evidenced by reduced pain over a 12-week treatment period in patients with advanced cancer. Previous studies have demonstrated consistent improvement of pain control after opioid rotation from morphine to methadone. In addition, the pilot study showed that there was a trend towards lower pain intensity when methadone used as first line opioid as compared to morphine. Researchers postulate that due to its superior analgesic effects, methadone will result in better pain control over time as compared to morphine.
- To determine whether methadone used as first line strong opioid is superior to morphine as evidenced by reduced frequency of neurotoxicity, dose escalation and treatment failure over a 12-week treatment period. Previous studies have demonstrated that patients develop increased pain or neurotoxicity after chronic use of morphine and require frequent opioid escalation. Researchers postulate that methadone will demonstrate lower opioid induced neurotoxicity, less frequent dose escalation and less treatment failure over 12-week treatment period as compared to morphine.
Read more
Secondary Aim:
-To perform an economic evaluation, comparing the costs and clinical benefits of methadone and morphine. Researchers will perform an evaluation that incorporates both treatment and potential "downstream" costs, as well as an examination of clinical benefits that incorporate preferences, to perform an appropriate economic comparison. We postulate that methadone and its associated costs will be cheaper than morphine. However, if one strategy is both more expensive and clinically superior than the other, researchers are prepared to perform an incremental cost-effectiveness analysis. In that case, researchers expect to show that the greater pharmaceutical costs involved with morphine will make its use not be a cost-effective strategy.
Read the detailed description
STUDY DRUGS:
MORPHINE is recommended as the first choice of strong pain killers by the World Health Organization Pain Relief Guidelines.
METHADONE is recommended as the second choice of strong pain killers.
SCREENING TESTS:
Before you can start treatment on this study, you will have "screening tests." These tests will help the doctor decide if you are eligible to take part in this study. The following tests and procedures will be performed:
- You will be asked about your level of pain.
- You will be asked about any pain killers you are currently taking.
- You will be asked about your history of allergies.
- Blood (about 1 teaspoon) will be drawn to check your kidney function.
STUDY GROUPS:
If you are found to be eligible to take part in this study, you will be randomly assigned (as in the toss of the coin) to 1 of 2 treatment groups. Group 1 will receive morphine while on-study. Group 2 will receive methadone. You will have an equal chance of being placed in either group. Neither you nor any of the study staff will know which study drug you are receiving. However, if needed for your safety, the study staff and study doctor will be able to find out which study drug you are receiving.
STUDY DRUG ADMINISTRATION:
If you are in Group 1, you will take 1 morphine capsule every 12 hours with water. If you are in Group 2, you will take 1 methadone capsule every 12 hours. Morphine and methadone should be swallowed whole.
You will be given additional capsules in another bottle to take for excessive pain. The additional capsules should be taken every 2 hours, as needed. If you need 3 or more of these additional doses in 24 hours, you should contact the study staff.
STUDY VISITS:
You will return to the clinic at the end of Weeks 1, 2, 4, 6, 8, 10 and 12 for questionnaires about your pain levels, ability to sleep, constipation, other side effects, and quality-of-life. You will complete 6 questionnaires at the Weeks 1, 2, 6, 10, and 11 visit. You will complete 11 questionnaires at the Weeks 4, 8, and 12 visits. Each questionnaire will take 1-3 minutes to complete. The visit with the research nurse will last about 45 minutes to 1 hour. Your study drug supply will also be checked. You also will be asked about your overall health, non-health care questions, and activity level. At these visits, you will receive a new prescription for a 2-week supply of the study drug.
PATIENT DIARY:
You will be given a patient diary booklet before you start taking the study drug. You will be asked to record when you take the study drug, other medications you may be taking, and any side effects you experience. You will fill out the patient diary once a day. It will take less than 2 minutes to complete.
For the first week of the treatment, you will be contacted by the research nurse every day either in person (if you are in the hospital) or by phone to check for pain, side effects, and the number of pills you have taken.
You are allowed to take other medication, such as medications for constipation, nausea, and other drugs during the study. All changes in medication for either symptoms or complications must be recorded by the research nurse at each study visit.
LENGTH OF STUDY:
After the visit at the end of Week 12, you will be off-study. You will be taken off-study early if your pain gets worse or intolerable side effects occur.
This is an investigational study. Both morphine and methadone are FDA approved and commercially available. You will not be told which study drug you were receiving. Up to 250 patients will take part in this study. Up to 200 will be enrolled at M. D. Anderson.
- Conditions
- Advanced Cancer, Solid Tumors
- Being tested
- Morphine, Methadone
- Keywords
- Advanced Cancer, Solid Tumors, Cancer Pain, Opioid Pain Killer, Morphine, Methadone
- Medical subject headings
- Cancer Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MorphineDrug
15 mg oral every 12 Hours; additional capsules taken every 2 hours as needed.
MethadoneDrug
5 mg orally every 12 hours; additional capsules every 2 hours as needed.
| Study group | Role | What they receive |
|---|---|---|
| Morphine Capsule | Active comparator | Morphine 15 mg slow release orally every 12 hours + additional doses as needed Receives: Drug: Morphine |
| Methadone Capsule | Active comparator | Methadone 5 mg orally every 12 hours + additional as needed doses up to 40-50 mg/day Receives: Drug: Methadone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Participant Pain Severity Score Measured Using Brief Pain Inventory
Brief Pain Inventory (BPI): Pain severity measured with BPI, which asks participants to rate pain for last 24 hours on 0 to 10 scales at its "worst", "least", "average " and "now". The scales are presented on a 10 cm line, with each number equidistant from the next. Each scale is bounded by the words "no pain' at the 0 end and "pain as bad as you can imagine" at the other. BPI used to determine whether methadone used as first line strong opioid is superior to morphine as evidenced by reduced pain over a 4 week (+/- 3 days) treatment period in participants with advanced cancer.
Measured: Comparing baseline and pain scores at 4 weeks (+/- 3 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Mar 2008 (estimated)
- Study startFeb 2008
- Primary completionJan 2015
- Study completionJan 2015
Why it stopped: Slow Accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Advanced CancerStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Eduardo Bruera, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00634010
- Sponsor's protocol ID
- 2007-0477
- Other IDs
- 1R01CA124481-01A1, NCI-2012-02126
- Status last verified
- Apr 2016
- First submitted
- 5 Mar 2008
- Last updated
- 9 May 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 9 May 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Morphine Versus Methadone As First Line Strong Opioid for Cancer Pain
- ClinicalTrials.gov ID
- NCT00634010
- Acronym / sponsor ID
- 2007-0477
- Conditions
- Advanced Cancer, Solid Tumors
- Keywords
- Advanced Cancer, Solid Tumors, Cancer Pain, Opioid Pain Killer, Morphine, Methadone
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow Accrual
- Enrolment
- 36 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Feb 2008
- Primary completion
- Jan 2015 (actual)
- Study completion
- Jan 2015 (actual)
- First posted
- 12 Mar 2008 (estimated)
- Results
- Posted 9 May 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Primary Aims:
- To determine whether methadone used as first line strong opioid is superior to morphine as evidenced by reduced pain over a 12-week treatment period in patients with advanced cancer. Previous studies have demonstrated consistent improvement of pain control after opioid rotation from morphine to methadone. In addition, the pilot study showed that there was a trend towards lower pain intensity when methadone used as first line opioid as compared to morphine. Researchers postulate that due to its superior analgesic effects, methadone will result in better pain control over time as compared to morphine.
- To determine whether methadone used as first line strong opioid is superior to morphine as evidenced by reduced frequency of neurotoxicity, dose escalation and treatment failure over a 12-week treatment period. Previous studies have demonstrated that patients develop increased pain or neurotoxicity after chronic use of morphine and require frequent opioid escalation. Researchers postulate that methadone will demonstrate lower opioid induced neurotoxicity, less frequent dose escalation and less treatment failure over 12-week treatment period as compared to morphine.
Secondary Aim:
-To perform an economic evaluation, comparing the costs and clinical benefits of methadone and morphine. Researchers will perform an evaluation that incorporates both treatment and potential "downstream" costs, as well as an examination of clinical benefits that incorporate preferences, to perform an appropriate economic comparison. We postulate that methadone and its associated costs will be cheaper than morphine. However, if one strategy is both more expensive and clinically superior than the other, researchers are prepared to perform an incremental cost-effectiveness analysis. In that case, researchers expect to show that the greater pharmaceutical costs involved with morphine will make its use not be a cost-effective strategy.
Detailed description
STUDY DRUGS:
MORPHINE is recommended as the first choice of strong pain killers by the World Health Organization Pain Relief Guidelines.
METHADONE is recommended as the second choice of strong pain killers.
SCREENING TESTS:
Before you can start treatment on this study, you will have "screening tests." These tests will help the doctor decide if you are eligible to take part in this study. The following tests and procedures will be performed:
- You will be asked about your level of pain.
- You will be asked about any pain killers you are currently taking.
- You will be asked about your history of allergies.
- Blood (about 1 teaspoon) will be drawn to check your kidney function.
STUDY GROUPS:
If you are found to be eligible to take part in this study, you will be randomly assigned (as in the toss of the coin) to 1 of 2 treatment groups. Group 1 will receive morphine while on-study. Group 2 will receive methadone. You will have an equal chance of being placed in either group. Neither you nor any of the study staff will know which study drug you are receiving. However, if needed for your safety, the study staff and study doctor will be able to find out which study drug you are receiving.
STUDY DRUG ADMINISTRATION:
If you are in Group 1, you will take 1 morphine capsule every 12 hours with water. If you are in Group 2, you will take 1 methadone capsule every 12 hours. Morphine and methadone should be swallowed whole.
You will be given additional capsules in another bottle to take for excessive pain. The additional capsules should be taken every 2 hours, as needed. If you need 3 or more of these additional doses in 24 hours, you should contact the study staff.
STUDY VISITS:
You will return to the clinic at the end of Weeks 1, 2, 4, 6, 8, 10 and 12 for questionnaires about your pain levels, ability to sleep, constipation, other side effects, and quality-of-life. You will complete 6 questionnaires at the Weeks 1, 2, 6, 10, and 11 visit. You will complete 11 questionnaires at the Weeks 4, 8, and 12 visits. Each questionnaire will take 1-3 minutes to complete. The visit with the research nurse will last about 45 minutes to 1 hour. Your study drug supply will also be checked. You also will be asked about your overall health, non-health care questions, and activity level. At these visits, you will receive a new prescription for a 2-week supply of the study drug.
PATIENT DIARY:
You will be given a patient diary booklet before you start taking the study drug. You will be asked to record when you take the study drug, other medications you may be taking, and any side effects you experience. You will fill out the patient diary once a day. It will take less than 2 minutes to complete.
For the first week of the treatment, you will be contacted by the research nurse every day either in person (if you are in the hospital) or by phone to check for pain, side effects, and the number of pills you have taken.
You are allowed to take other medication, such as medications for constipation, nausea, and other drugs during the study. All changes in medication for either symptoms or complications must be recorded by the research nurse at each study visit.
LENGTH OF STUDY:
After the visit at the end of Week 12, you will be off-study. You will be taken off-study early if your pain gets worse or intolerable side effects occur.
This is an investigational study. Both morphine and methadone are FDA approved and commercially available. You will not be told which study drug you were receiving. Up to 250 patients will take part in this study. Up to 200 will be enrolled at M. D. Anderson.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Morphine Capsule | Active comparator | Drug: MorphineMorphine 15 mg slow release orally every 12 hours + additional doses as needed |
| Methadone Capsule | Active comparator | Drug: MethadoneMethadone 5 mg orally every 12 hours + additional as needed doses up to 40-50 mg/day |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Patient has pain caused by advanced cancer (local recurrence or metastatic disease)
- Patient reporting average pain score for the last 24 hours is >/= 4 on a numerical scale from 0 to 10 (0= no pain, 10=the worst possible pain).
- Patient is receiving mild opioids (e.g. propoxyphene, codeine, tramadol, hydrocodone), mixed agonist/antagonist (e.g. buprenorphine) or no opioids.
- Patient requires initiation of strong opioid for cancer pain.
- Patient has the ability to receive morphine or methadone orally.
Key exclusion criteria (5 listed)
- Patient has concurrent strong opioid for cancer pain, such as morphine, hydromorphone, oxycodone, meperidine, fentanyl, oral transmucosal fentanyl citrate (OTFC), sufentanil, methadone, levorphanol, transdermal fentanyl.
- Patient is receiving radiation therapy for pain control.
- Patient is receiving drugs that interacting with methadone, such as (delavirdine, fluconazole, fluvoxamine, bravavir, amprenavir, efavirenz, lopinavir, nelfinavir, nevirapine, carbamazepine, dexamethasone (Patients receiving short term chemotherapy-related doses are permitted) , phenytoin, rifampin, or grapefruit,).
- Patients are determined incapable of completing the evaluation forms.
- Severe hypotension, acute or severe asthma, paralytic ileus, gastrointestinal obstruction, severe respiratory depression.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Morphine15 mg oral every 12 Hours; additional capsules taken every 2 hours as needed. | Drug | Morphine Capsule |
| Methadone5 mg orally every 12 hours; additional capsules every 2 hours as needed. | Drug | Methadone Capsule |
Primary outcome
Participant Pain Severity Score Measured Using Brief Pain Inventory
Time frame: Comparing baseline and pain scores at 4 weeks (+/- 3 days)
Brief Pain Inventory (BPI): Pain severity measured with BPI, which asks participants to rate pain for last 24 hours on 0 to 10 scales at its "worst", "least", "average " and "now". The scales are presented on a 10 cm line, with each number equidistant from the next. Each scale is bounded by the words "no pain' at the 0 end and "pain as bad as you can imagine" at the other. BPI used to determine whether methadone used as first line strong opioid is superior to morphine as evidenced by reduced pain over a 4 week (+/- 3 days) treatment period in participants with advanced cancer.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 May 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- University of Texas MD Anderson Cancer Center WebsiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Eduardo Bruera, MD principal investigator
M.D. Anderson Cancer Center
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Morphine and Methadone in people with Advanced Cancer and Solid Tumors, run by M.D. Anderson Cancer Center at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 9 May 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 May 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Participant Pain Severity Score Measured Using Brief Pain Inventory (time frame: Comparing baseline and pain scores at 4 weeks (+/- 3 days)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 May 2016.