Treatment for Chronic Pain in Patients With Advanced Cancer

• Sponsor: NCIC Clinical Trials Group
• Information provided by (Responsible Party): Canadian Cancer Trials Group ( NCIC Clinical Trials Group )

Study Description

Brief Summary:

RATIONALE: Different drug formulations and combinations of drugs may help patients with chronic pain live more comfortably. It is not yet known which regimen is most effective for chronic pain.

PURPOSE: Randomized phase III trial to compare the effectiveness of different morphine formulations with or without dextromethorphan in treating chronic pain in patients who have advanced cancer.

Condition or disease	Intervention/treatment	Phase
Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Pain; Precancerous/Nonmalignant Condition; Small Intestine Cancer; Unspecified Adult Solid Tumor, Protocol Specific	Drug: dextromethorphan hydrobromide; Drug: morphine sulfate	Phase 3

Detailed Description:

OBJECTIVES:

• Compare the analgesic efficacy of two formulations of morphine (Statex SR versus MS-Contin) in patients requiring morphine for the treatment of chronic cancer pain.
• Compare the effect of these 2 formulations of morphine on the total analgesic consumption, sleep disturbances, sleep and nausea, responses of different types of pain, and toxic effects experienced in the two treatment groups.
• Compare the effect of coadministration of morphine and dextromethorphan versus morphine and placebo on pain control in the respective patient groups (phase B).
• Compare the effect of morphine and dextromethorphan or placebo on total analgesic consumption, sleep disturbances, sleep and nausea, responses of different types of pain, and toxic effects on the two treatment groups (phase B).

OUTLINE: This is a randomized, double-blind, parallel-group, multicenter study. Patients are stratified by stabilization dose (less than 120 mg/day vs greater than 120 mg/day of morphine) and institution in phase A, and neuropathic pain (yes vs no) in phase B.

• Phase A: Patients are randomized to receive oral morphine in one of two formulations (MS Contin or Statex SR) every 12 hours for 7 days.
• Phase B: Eligible patients from phase A who have taken no more than 2 breakthrough doses of analgesic per day in the previous 2 days are re-randomized to receive dose escalated oral dextromethorphan capsules or placebo every 4 hours, and oral morphine tablets every 12 hours for 14 days.
• Phase C: All patients fulfilling entry criteria at the end of phase A or any time during phase B may receive compassionate use morphine tablets for up to 90 days.

Patients complete a pain diary twice each day during treatment.

PROJECTED ACCRUAL: A total of 120 patients will be accrued for this study.

Study Design

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Study Type :	Interventional (Clinical Trial)
Allocation:	Randomized
Masking:	Double
Primary Purpose:	Supportive Care
Official Title:	A Phase III Double-Blind Equivalence Study of Two Different Formulations of Slow-Release Morphine Followed by a Randomization Between Dextromethorphan or Placebo Plus Statex SR for Chronic Cancer Pain Relief in Terminally Ill Patients
Study Start Date :	December 1998
Actual Primary Completion Date :	September 2001
Actual Study Completion Date :	February 2009

Arms and Interventions

Outcome Measures

Eligibility Criteria

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Ages Eligible for Study:	16 Years to 120 Years (Child, Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically proven advanced cancer with chronic pain
• Cancer pain requiring strong opioids having an average pain score of less than 6/10 on the visual analog scale within last 24 hours
• Pain managed by a stable maintenance dose of MS-Contin formulation of morphine for at least 2 days with no more than 2 breakthrough immediate release morphine doses per 24 hours
• Pain that is expected to be controlled by a stable and adequate total daily dose of sustained release morphine for the first 7 days of the study

PATIENT CHARACTERISTICS:

Age:

• 16 and over

Performance status:

• Not specified

Life expectancy:

• At least 2 months

Hematopoietic:

• Not specified

Hepatic:

• SGOT or SGPT no greater than 3 times upper limit of normal (ULN)
• No liver disease

Renal:

• Creatinine no greater than 2 times ULN
• No kidney failure

Pulmonary:

• No clinically significant respiratory depression
• No severe obstructive airway disease

Other:

• Fluent in English or French
• No known hypersensitivity or allergy to study medications or components or other multiple drug allergies
• Normal cognition defined by the Folstein Mini-Mental State Questionnaire (at least 24/30 correct)

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• At least 14 days since prior chemotherapy

Endocrine therapy:

• Concurrent steroids allowed

Radiotherapy:

• At least 14 days since prior analgesic radiotherapy

Surgery:

• Not specified

Other:

• At least 3 months since prior investigational agents
• At least 1 month since prior clinical study
• No concurrent analgesics other than morphine
• No other concurrent medications containing dextromethorphan
• Concurrent antidepressant medication allowed
• Concurrent nonsteroidal antiinflammatory drugs allowed
• At least 14 days since prior monoamine oxidase (MAO) inhibitors
• No concurrent MAO inhibitors

Contacts and Locations

Locations

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Canada, Alberta
Cross Cancer Institute
Edmonton, Alberta, Canada, T6G 1Z2
Canada, Newfoundland and Labrador
Newfoundland Cancer Treatment and Research Foundation
St. Johns, Newfoundland and Labrador, Canada, A1B 3V6
Canada, Ontario
Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
McGill University
Montreal, Quebec, Canada, H2W 1S6

Sponsors and Collaborators

NCIC Clinical Trials Group

Investigators

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Study Chair:	Eduardo Bruera, MD	M.D. Anderson Cancer Center

More Information

Publications of Results:

MacDonald S, Dudgeon DJ, Bruera E, et al.: A phase III double-blind equivalence study of two different formulations of slow-release morphine followed by a randomization between dextromethorphan or placebo plus Statex SR for chronic cancer pain relief in terminally ill patients. [Abstract] Proceedings of the American Society of Clinical Oncology 21: A-1521, 2002.

Dudgeon DJ, Bruera E, Gagnon B, Watanabe SM, Allan SJ, Warr DG, MacDonald SM, Savage C, Tu D, Pater JL. A phase III randomized, double-blind, placebo-controlled study evaluating dextromethorphan plus slow-release morphine for chronic cancer pain relief in terminally ill patients. J Pain Symptom Manage. 2007 Apr;33(4):365-71.

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Responsible Party:	NCIC Clinical Trials Group
ClinicalTrials.gov Identifier:	NCT00003687 History of Changes
Other Study ID Numbers:	SC17; CAN-NCIC-SC17; CDR0000066789 ( Other Identifier: PDQ )
First Posted:	January 27, 2003
Last Update Posted:	November 28, 2016
Last Verified:	March 2010
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Undecided

Keywords provided by Canadian Cancer Trials Group ( NCIC Clinical Trials Group ):

stage III adult Hodgkin lymphoma; stage IV adult Hodgkin lymphoma; monoclonal gammopathy of undetermined significance; recurrent adult Hodgkin lymphoma; stage III cutaneous T-cell non-Hodgkin lymphoma; stage IV cutaneous T-cell non-Hodgkin lymphoma; recurrent cutaneous T-cell non-Hodgkin lymphoma; isolated plasmacytoma of bone; extramedullary plasmacytoma; refractory multiple myeloma; Waldenstrom macroglobulinemia; stage III multiple myeloma; stage III chronic lymphocytic leukemia; stage IV chronic lymphocytic leukemia; recurrent adult acute myeloid leukemia

recurrent adult acute lymphoblastic leukemia; relapsing chronic myelogenous leukemia; refractory chronic lymphocytic leukemia; small intestine lymphoma; unspecified adult solid tumor, protocol specific; chronic phase chronic myelogenous leukemia; accelerated phase chronic myelogenous leukemia; blastic phase chronic myelogenous leukemia; meningeal chronic myelogenous leukemia; untreated adult acute lymphoblastic leukemia; untreated adult acute myeloid leukemia; adult acute myeloid leukemia in remission; adult acute lymphoblastic leukemia in remission; polycythemia vera; chronic idiopathic myelofibrosis

Additional relevant MeSH terms:

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Lymphoma; Syndrome; Leukemia; Multiple Myeloma; Neoplasms, Plasma Cell; Myelodysplastic Syndromes; Preleukemia; Plasmacytoma; Myeloproliferative Disorders; Intestinal Neoplasms; Precancerous Conditions; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases	Immunoproliferative Disorders; Immune System Diseases; Disease; Pathologic Processes; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Bone Marrow Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site