Methadone Hydrochloride as First-Line Therapy in Treating Patients With Chronic Neuropathic Cancer Pain - Full Text View

Sponsor:	NCIC Clinical Trials Group
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00930332

Purpose

RATIONALE: Methadone hydrochloride may reduce chronic neuropathic pain in patients with cancer.

PURPOSE: This phase I trial is studying the side effects and best dose of methadone hydrochloride as first-line therapy in treating patients with chronic neuropathic cancer pain.

Condition	Intervention	Phase
Nausea and Vomiting Pain Sleep Disorders Unspecified Adult Solid Tumor, Protocol Specific	Drug: methadone hydrochloride Other: questionnaire administration Procedure: management of therapy complications	Phase I

Study Type:	Interventional
Study Design:	Supportive Care, Non-Randomized, Open Label
Official Title:	A Phase I Study to Determine the Dose of Methadone as a First Line Agent in the Treatment of Chronic Neuropathic Cancer Pain

Resource links provided by NLM:

MedlinePlus related topics: Cancer Nausea and Vomiting Sleep Disorders

Drug Information available for: Methadone Methadone hydrochloride

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Optimum starting dose [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Pain control as assessed by the number and timing of breakthrough analgesics, the number of episodes of breakthrough pain, the total daily dose of methadone, and the average pain scores [ Designated as safety issue: No ]
Adverse events (including respiratory depression) according to NCI CTCAE v3.0 criteria [ Designated as safety issue: Yes ]
Frequency and severity of sleep disturbance from pain [ Designated as safety issue: No ]
Feasibility of recruiting patients [ Designated as safety issue: No ]

Estimated Enrollment:	60
Study Start Date:	April 2009
Estimated Primary Completion Date:	September 2010 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

To determine the optimum starting dose (defined as the dose that does not require modification within the first 4 days of treatment for lack of efficacy or the occurrence of adverse events) of methadone hydrochloride as a first-line opioid treatment in patients with chronic neuropathic cancer pain.

Secondary

To assess the number and timing of breakthrough analgesic usage.
To assess the number of episodes of breakthrough pain.
To assess the total daily dose of methadone hydrochloride.
To assess the average pain score.
To determine the safety and adverse event profile of methadone hydrochloride as a first-line opioid in the treatment of chronic neuropathic cancer pain.
To assess the frequency and severity of sleep disturbance associated with the use of methadone hydrochloride.
To determine the feasibility of recruiting patients with chronic neuropathic cancer pain in a reasonable time frame for a future phase III study of methadone hydrochloride vs morphine.

OUTLINE: This is a multicenter study. Patients are assigned to a group according to their average daily dosage of morphine-equivalent for the 3 full days prior to study entry (≤ 45 mg/day OR > 45 but ≤ 75 mg/day).

Patients receive oral methadone hydrochloride at various doses every 8 hours. Patients also may receive breakthrough oral methadone hydrochloride every 2 hours, as needed, for up to 6 breakthrough analgesics per day. Treatment continues for up to 35 days. Treatment stops if the patient has well-controlled pain or experiences intolerable side effects.

Patients complete the Short-Form McGill Pain Questionnaire at baseline. Patients rate their pain according to questions from the Brief Pain Inventory on a scale of 0 (no pain) to 10 (worst pain imaginable) to best describe pain at its worst in the last 24 hours, pain at its least in the last 24 hours, pain on average, and pain right now; record the number and timing of breakthrough analgesic usage, the number of episodes of breakthrough pain, and the total daily dose of methadone hydrochloride; and complete nausea and sleep assessments once daily on days 1-14.

After completion of study treatment, patients are followed at 4, 6-7, and 28 days.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Patients diagnosed with cancer and experiencing chronic neuropathic pain syndrome
- Pain syndrome diagnosed by the investigator
- Pain syndrome related to the effects of cancer or its treatment (i.e., chemotherapy, radiotherapy, and surgery)
- Meets 1 of the following criteria:
  - Need to be started on strong opioids
  - Require an increase in opioid dose and are currently taking ≤ 75 mg of total daily dose of oral morphine equivalent
Experiencing pain for ≥ 4 weeks with an average pain score of ≥ 4 or a worst pain score of ≥ 5 (using the 0-10 Brief Pain Inventory Scale) during the past 24 hours
Requires strong opioids to control pain and is using an oral morphine-equivalent dose of 0-75 mg per day, on average, including breakthrough analgesia, within the past 3 full calendar days
Mixed pain syndrome allowed provided the neuropathic component is the predominant pain
Meets 1 of the following criteria:
- Receiving concurrent chemotherapy but the chronic neuropathic pain is not related to this treatment and is not expected to improve or worsen because of this therapy
- Received prior chemotherapy but discontinued treatment, has not received chemotherapy within the past 7 days, and no further chemotherapy is planned
- No prior chemotherapy

PATIENT CHARACTERISTICS:

Karnofsky performance status 40-100%
ALT and AST < 3 times upper limit of normal (ULN)
Creatinine < 2 times ULN
No other known laboratory abnormality that, in the investigator's opinion, would contraindicate study participation
Not pregnant or nursing
Fertile patients must use effective contraception
Mini-Mental State Examination score ≥ 25/30
Able to speak, read, and write in either English or French
Willing to complete study diary and questionnaires
Available for study treatment and follow up (i.e., within reasonable geographical limits of the participating center)
Able to swallow and tolerate oral medications
Patients with prior exposure to methadone hydrochloride must be able to tolerate it
No intractable nausea and vomiting
No presence or history of unstable disease or condition that would, in the investigator's opinion, preclude patient participation in study treatment, such as:
- Head injury
- Increased intracranial pressure
- Uncontrolled seizures
- Uncontrolled asthma
- Decompensated chronic obstructive pulmonary disease
- Untreated prostate hypertrophy
- Acute abdominal conditions
- Untreated hyperthyroidism and Addison disease
- Increased cerebrospinal fluid pressure
- Urethral stricture
- Severe cardiac arrhythmias (especially prolonged QT interval)
- Symptomatic hypotension
- Toxic psychosis
- Cor pulmonale
- Sleep apnea
- Severe obesity
- Kyphoscoliosis
- Myxedema
- Central nervous system depression
- Coma
No history of significant alcohol, analgesic, or narcotic substance abuse within the past 6 months
Able physically and mentally to answer questions and comply with study treatment
No patient who lives alone and cannot access at least 1 caregiver who can monitor on a daily basis at home

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
More than 3 weeks since prior radiopharmaceutical treatment or radiotherapy
Concurrent co-analgesics and medications that can affect methadone hydrochloride metabolism allowed provided patients have been on a stable dose for the past 3-5 days and ≥ 5 half lives have passed since any change in dose
Not scheduled to start chemotherapy during the study treatment
Not planning on starting or discontinuing medication associated with modified methadone hydrochloride clearance during study treatment
No concurrent therapeutic procedure that is likely to influence pain intensity during the study period
No concurrent other opioid medications
No other concurrent methadone hydrochloride

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00930332

Sponsors and Collaborators

NCIC Clinical Trials Group

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Bruno Gagnon, MD, MSC

McGill Cancer Centre at McGill University

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000641372, CAN-NCIC-SC22
Study First Received:	June 27, 2009
Last Updated:	February 5, 2010
ClinicalTrials.gov Identifier:	NCT00930332 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

sleep disorders
nausea and vomiting
unspecified adult solid tumor, protocol specific
pain

Additional relevant MeSH terms:

Respiratory System Agents
Disease
Vomiting
Signs and Symptoms, Digestive
Physiological Effects of Drugs
Nervous System Diseases
Central Nervous System Depressants
Sleep Disorders
Narcotics
Pharmacologic Actions
Signs and Symptoms

Methadone
Pathologic Processes
Sensory System Agents
Mental Disorders
Therapeutic Uses
Neurologic Manifestations
Peripheral Nervous System Agents
Analgesics
Antitussive Agents
Central Nervous System Agents
Analgesics, Opioid

ClinicalTrials.gov processed this record on February 08, 2010