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

NCT00930332 | Terminated Phase 1 DMC

• 3 other identifiers: SC22CAN-NCIC-SC22CDR0000641372
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 7

Brief Summary

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.

Conditions

Nausea and Vomiting; Pain; Sleep Disorders; Unspecified Adult Solid Tumor, Protocol Specific

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Optimum starting dose

  28 days

Secondary Outcomes (4)

• 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

  28 days

• Adverse events (including respiratory depression) according to NCI CTCAE v3.0 criteria

  28 days

• Frequency and severity of sleep disturbance from pain

  28 days

• Feasibility of recruiting patients

  28 days

Study Arms (2)

Arm A: Methadone

ACTIVE COMPARATOR

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; Other: questionnaire administration; Procedure: management of therapy complications

Arm B: Methadone

ACTIVE COMPARATOR

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; Other: questionnaire administration; Procedure: management of therapy complications

Interventions

methadone hydrochloride DRUG

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)

Arm A: Methadone; Arm B: Methadone

questionnaire administration OTHER

within 48 hours of registration

Arm A: Methadone; Arm B: Methadone

management of therapy complications PROCEDURE

if required

Arm A: Methadone; Arm B: Methadone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• NCIC Clinical Trials Group: lead

Study Sites (7)

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

BCCA - Cancer Centre for the Southern Interior

Kelowna, British Columbia, V1Y 5L3, Canada

Location

BCCA - Vancouver Cancer Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

CancerCare Manitoba

Winnipeg, Manitoba, R3E 0V9, Canada

Location

Cancer Centre of Southeastern Ontario at Kingston

Kingston, Ontario, K7L 5P9, Canada

Location

Univ. Health Network-Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

McGill University - Dept. Oncology

Montreal, Quebec, H2W 1S6, Canada

Location

MeSH Terms

Conditions

Nausea; Vomiting; Pain; Sleep Wake Disorders

Interventions

Methadone

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurologic Manifestations; Nervous System Diseases; Mental Disorders

Intervention Hierarchy (Ancestors)

Ketones; Organic Chemicals

Study Officials

• Bruno Gagnon, MD, MSC

  McGill Cancer Centre at McGill University

  STUDY CHAIR

• Ray Viola

  Queen's University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 27, 2009
• First Posted: June 30, 2009
• Study Start: June 17, 2010
• Primary Completion: January 6, 2012
• Study Completion: January 6, 2012
• Last Updated: February 12, 2024

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (7)