MDACC Study Summary 2007-0477

Study Summary
No. 2007-0477:.......Other Supportive......Eduardo Bruera......Palliative Care & Rehabilitation Medicine

Study Summary Title



Study Summary Number:	2007-0477

Study Title:	Morphine versus Methadone As First Line Strong Opioid for Cancer Pain

Physician

New Patient Referral



Name:	Eduardo Bruera	Patients Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Dept:	Palliative Care & Rehabilitation Medicine	Referring MD Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Phone:	713-792-6085 Contact us about clinical trials

General Information



Disease Group:	Other Supportive	Supported By:	NCI

Phase of Study:	Phase III	Return Visit:	Week 1 (Day 8), Week 2 ( Day 15), Week 4 (Day 29), Week 8 (Day 57),Week 12 (Day 85).

Treatment Agents:	Methadone Morphine Sulfate	Home Care:	Study drug is given orally and is given daily. Patient must take the study drug at home if they are discharged from the hospital.

Treatment Loc:	Both at MDACC & outside MDACC at one or more Collaborating Sites or Institutions

Estimated Length of Stay in Houston:	Not required by the protocol.


Description/ Intervention:	The goal of this clinical research study is to learn if methadone (a type of opioid pain killer) is more effective and has less side effects than morphine (another type of opioid pain killer). The costs will also be compared.

Study Objectives / Outcomes

In this NCI R01 grant supported study, we hope to achieve the following aims :

Primary Aim #1:
Aim #1a. 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 patients with advanced cancer. Our previous studies have demonstrated consistent improvement of pain control after opioid rotation from morphine to methadone. In addition, our pilot study showed that there was a trend towards lower pain intensity when methadone used as first line opioid as compared to morphine. We postulate that due to its superior analgesic effects, methadone will result in better pain control over time as compared to morphine.
Aim #1b. 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 4-week (+/- 3 days) treatment period. Previous studies have demonstrated that patients develop increased pain or neurotoxicity after chronic use of morphine and require frequent opioid escalation. We postulate that methadone will demonstrate lower opioid induced neurotoxicity, less frequent dose escalation and less treatment failure over 4-week (+/- 3 days) treatment period as compared to morphine.

Secondary Aims:
Aim #2: To perform an economic evaluation, comparing the costs and clinical benefits of methadone and morphine. We 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, we are prepared to perform an incremental cost-effectiveness analysis. In that case, we expect to show that the greater pharmaceutical costs involved with morphine will make its use not be a cost-effective strategy.

Study Status Information



Study Activation / Registration Date:	02/22/2008

IRB Review and Approval Date:	10/10/2007

Study Type:	Phase Iii

Recruitment Status:	Closed

Projected Accrual:	250

Enrollment Eligibility

If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:

1) Patient has pain caused by advanced cancer (local recurrence or metastatic disease)

2) 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).

3) Patient is receiving mild opioids (e.g. propoxyphene, codeine, tramadol, hydrocodone), mixed agonist/antagonist (e.g. buprenorphine) or no opioids.

4) Patient requires initiation of strong opioid for cancer pain.

5) Patient has the ability to receive morphine or methadone orally.

6) 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).

7) Patient has normal cognition defined as normal state of arousal and absence of obvious clinical findings of confusion, memory or concentration deficit.

8) Patient has normal renal function (creatinine and BUN within normal limits) </= 4 weeks of study entry.

9) Patient's performance status (ECOG) is 3 or less.

10) Patient is willing to sign written informed consent.

11) Patient is 18 years of age or older.

12) Patient is able to return to clinic for evaluation by physician day 8 , 15 , 29, 57 and 85 ( +/- 3 days) during study period.

Exclusion Criteria:

1) Patient has concurrent strong opioid for cancer pain, such as morphine, hydromorphone, oxycodone, meperidine, fentanyl, oral transmucosal fetanyl citrate (OTFC), sufentanil, methadone, levorphanol, transdermal fentanyl.

2) Patient is receiving radiation therapy for pain control.

3) Patient is receiving drugs that interacting with methadone, such as (delavirdine, fluconazole, fluvoxamine, bacavir, amprenavir, efavirenz, iopinavir, nelfinavir, nevirapine, carbamazepine, dexamethasone (Patients receiving short term chemotherapy-related doses are permitted) , phenytoin, rifampin, or grapefruit,).

4) Patients are determined incapable of completing the evaluation forms.

5) Severe hypotension, acute or severe asthma, paralytic ileus, gastrointenstinal obstruction, severe respiratory depression.

Links

Registration Number: NCT00634010
Study Information on Clinical Trials Registry (clinicaltrials.gov)