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

Sponsor:	NCIC Clinical Trials Group
Information provided by:	NCIC Clinical Trials Group
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:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Supportive Care
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 NCIC Clinical Trials Group:

Primary Outcome Measures:

Optimum starting dose [ Time Frame: 28 days ] [ 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 [ Time Frame: 28 days ] [ Designated as safety issue: No ]
Adverse events (including respiratory depression) according to NCI CTCAE v3.0 criteria [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
Frequency and severity of sleep disturbance from pain [ Time Frame: 28 days ] [ Designated as safety issue: No ]
Feasibility of recruiting patients [ Time Frame: 28 days ] [ Designated as safety issue: No ]

Enrollment:	8
Study Start Date:	April 2009
Estimated Study Completion Date:	September 2011
Estimated Primary Completion Date:	September 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Arm A: Methadone Level 1: 1 mg q8h, breakthrough 1 mg q2h* (maximum 6 BTA** per day) Level 2: 2 mg q8h, breakthrough 1 mg q2h* (maximum 6 BTA per day) Level 3: 3 mg q8h, breakthrough 1 mg q2h* (maximum 6 BTA per day)	Drug: methadone hydrochloride Level 1: 1 mg q8h, breakthrough 1 mg q2h* (maximum 6 BTA** per day) Level 2: 2 mg q8h, breakthrough 1 mg q2h* (maximum 6 BTA per day) Level 3: 3mg q8h, breakthrough 1 mg q2h* (maximum 6 BTA per day) OR Level 1: 2 mg q8h, breakthrough 1 mg q2h* (maximum 6 BTA per day) Level 2: 3 mg q8h, breakthrough 1 mg q2h* (maximum 6 BTA per day) Level 3: 4 mg q8h, breakthrough 1 mg q2h* (maximum 6 BTA per day) Other: questionnaire administration within 48 hours of registration Procedure: management of therapy complications if required
Active Comparator: Arm B: Methadone Level 1: 2 mg q8h, breakthrough 1 mg q2h* (maximum 6 BTA per day) Level 2: 3 mg q8h, breakthrough 1 mg q2h* (maximum 6 BTA per day) Level 3: 4 mg q8h, breakthrough 1 mg q2h* (maximum 6 BTA per day)	Drug: methadone hydrochloride Level 1: 1 mg q8h, breakthrough 1 mg q2h* (maximum 6 BTA** per day) Level 2: 2 mg q8h, breakthrough 1 mg q2h* (maximum 6 BTA per day) Level 3: 3mg q8h, breakthrough 1 mg q2h* (maximum 6 BTA per day) OR Level 1: 2 mg q8h, breakthrough 1 mg q2h* (maximum 6 BTA per day) Level 2: 3 mg q8h, breakthrough 1 mg q2h* (maximum 6 BTA per day) Level 3: 4 mg q8h, breakthrough 1 mg q2h* (maximum 6 BTA per day) Other: questionnaire administration within 48 hours of registration Procedure: management of therapy complications if required

Arms

Assigned Interventions

Active Comparator: Arm A: Methadone

Level 1: 1 mg q8h, breakthrough 1 mg q2h* (maximum 6 BTA** per day)

Level 2: 2 mg q8h, breakthrough 1 mg q2h* (maximum 6 BTA per day)

Level 3: 3 mg q8h, breakthrough 1 mg q2h* (maximum 6 BTA per day)

Drug: methadone hydrochloride

Level 1: 1 mg q8h, breakthrough 1 mg q2h* (maximum 6 BTA** per day)

Level 2: 2 mg q8h, breakthrough 1 mg q2h* (maximum 6 BTA per day)

Level 3: 3mg q8h, breakthrough 1 mg q2h* (maximum 6 BTA per day)

OR

Level 1: 2 mg q8h, breakthrough 1 mg q2h* (maximum 6 BTA per day)

Level 2: 3 mg q8h, breakthrough 1 mg q2h* (maximum 6 BTA per day)

Level 3: 4 mg q8h, breakthrough 1 mg q2h* (maximum 6 BTA per day)

Other: questionnaire administration

within 48 hours of registration

Procedure: management of therapy complications

if required

Active Comparator: Arm B: Methadone

Level 1: 2 mg q8h, breakthrough 1 mg q2h* (maximum 6 BTA per day)

Level 2: 3 mg q8h, breakthrough 1 mg q2h* (maximum 6 BTA per day)

Level 3: 4 mg q8h, breakthrough 1 mg q2h* (maximum 6 BTA per day)

Drug: methadone hydrochloride

Level 1: 1 mg q8h, breakthrough 1 mg q2h* (maximum 6 BTA** per day)

Level 2: 2 mg q8h, breakthrough 1 mg q2h* (maximum 6 BTA per day)

Level 3: 3mg q8h, breakthrough 1 mg q2h* (maximum 6 BTA per day)

OR

Level 1: 2 mg q8h, breakthrough 1 mg q2h* (maximum 6 BTA per day)

Level 2: 3 mg q8h, breakthrough 1 mg q2h* (maximum 6 BTA per day)

Level 3: 4 mg q8h, breakthrough 1 mg q2h* (maximum 6 BTA per day)

Other: questionnaire administration

within 48 hours of registration

Procedure: management of therapy complications

if required

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

Locations

Canada, Alberta
Cross Cancer Institute
Edmonton, Alberta, Canada, T6G 1Z2
Canada, British Columbia
BCCA - Cancer Centre for the Southern Interior
Kelowna, British Columbia, Canada, V1Y 5L3
BCCA - Vancouver Cancer Centre
Vancouver, British Columbia, Canada, V5Z 4E6
Canada, Manitoba
CancerCare Manitoba
Winnipeg, Manitoba, Canada, R3E 0V9
Canada, Ontario
Cancer Centre of Southeastern Ontario at Kingston
Kingston, Ontario, Canada, K7L 5P9
Univ. Health Network-Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
McGill University - Dept. Oncology
Montreal, Quebec, Canada, H2W 1S6

Sponsors and Collaborators

NCIC Clinical Trials Group

Investigators

Study Chair:	Bruno Gagnon, MD, MSC	McGill Cancer Centre at McGill University
Study Chair:	Ray Viola	Kingston General Hospital

More Information

No publications provided

Responsible Party:	Ralph Meyer, M.D., NCIC Clinical Trials Group
ClinicalTrials.gov Identifier:	NCT00930332 History of Changes
Other Study ID Numbers:	SC22, CAN-NCIC-SC22, CDR0000641372
Study First Received:	June 27, 2009
Last Updated:	July 28, 2011
Health Authority:	Canada: Ethics Review Committee

Keywords provided by NCIC Clinical Trials Group:

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

Additional relevant MeSH terms:

Nausea
Vomiting
Sleep Disorders
Parasomnias
Signs and Symptoms, Digestive
Signs and Symptoms
Nervous System Diseases
Neurologic Manifestations
Mental Disorders
Methadone
Analgesics, Opioid

Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Central Nervous System Depressants
Antitussive Agents
Respiratory System Agents
Narcotics

ClinicalTrials.gov processed this record on February 09, 2012