Comment Period Extended to 3/23/2015 for Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Opioid Titration Order Sheet or Standard Care in Treating Patients With Cancer Pain

This study has been completed.
Information provided by (Responsible Party):
Nancy Wells, Vanderbilt-Ingram Cancer Center Identifier:
First received: April 23, 2008
Last updated: August 4, 2012
Last verified: August 2012

RATIONALE: An Opioid Titration Order Sheet that allows healthcare providers to adjust the dose and schedule of pain medication may help improve pain treatment for patients with cancer. It is not yet known whether the use of an Opioid Titration Order Sheet is more effective than standard care in treating pain caused by cancer.

PURPOSE: This randomized phase III trial is studying an Opioid Titration Order Sheet to see how well it works compared with standard care in treating patients with cancer pain.

Condition Intervention Phase
Brain and Central Nervous System Tumors
Chronic Myeloproliferative Disorders
Lymphoproliferative Disorder
Multiple Myeloma and Plasma Cell Neoplasm
Myelodysplastic Syndromes
Myelodysplastic/Myeloproliferative Neoplasms
Precancerous Condition
Unspecified Adult Solid Tumor, Protocol Specific
Other: educational intervention
Other: Titrated pain management
Other: questionnaire administration
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Supportive Care
Official Title: Phase III Randomized Trial of an Opioid Titration Order Sheet Compared to Standard of Care in Patients With Cancer Related Pain.

Resource links provided by NLM:

Genetic and Rare Diseases Information Center resources: AL Amyloidosis Acute Lymphoblastic Leukemia Acute Monoblastic Leukemia Acute Myeloblastic Leukemia Type 5 Acute Myelocytic Leukemia Acute Myeloid Leukemia, Adult Acute Non Lymphoblastic Leukemia Anaplastic Large Cell Lymphoma Anaplastic Plasmacytoma Angioimmunoblastic Lymphadenopathy With Dysproteinemia Angioimmunoblastic T-cell Lymphoma B-cell Lymphomas Burkitt Lymphoma Chronic Lymphocytic Leukemia Chronic Myeloid Leukemia Chronic Myelomonocytic Leukemia Chronic Myeloproliferative Disorders Chronic Neutrophilic Leukemia Cutaneous T-cell Lymphoma Essential Thrombocythemia Follicular Lymphoma Hairy Cell Leukemia Hodgkin Lymphoma Hypereosinophilic Syndrome Large Granular Lymphocyte Leukemia Leukemia, B-cell, Chronic Leukemia, Myeloid Leukemia, T-cell, Chronic Lymphoblastic Lymphoma Lymphoma, Large-cell Lymphoma, Large-cell, Immunoblastic Lymphoma, Small Cleaved-cell, Diffuse Lymphomatoid Granulomatosis Lymphosarcoma Mantle Cell Lymphoma Monoclonal Gammopathy of Undetermined Significance Multiple Myeloma Mycosis Fungoides Myelodysplastic Syndromes Myelodysplastic/myeloproliferative Disease Myelofibrosis Plasmablastic Lymphoma Polycythemia Vera Sezary Syndrome Small Non-cleaved Cell Lymphoma Squamous Cell Carcinoma of the Head and Neck Systemic Mastocytosis Waldenstrom Macroglobulinemia
U.S. FDA Resources

Further study details as provided by Vanderbilt-Ingram Cancer Center:

Primary Outcome Measures:
  • Pain Intensity [ Time Frame: Baseline(Week 0) to week 8, Total time frame is 9 weeks. ] [ Designated as safety issue: No ]

    Patients in each arm will each have 9 measures: daily scores averaged over 1 week with baseline to week 8:

    1. Average daily pain intensity 0 (no pain) to 10 (worst) scale
    2. Worst daily pain intensity 0 (no pain) to 10 (worst) scale

  • Pain-related Distress [ Time Frame: Baseline(Week 0) to week 8, Total time frame is 9 weeks. ] [ Designated as safety issue: No ]
    Patients in each arm will each have 9 measures: daily scores averaged over 1 week with baseline to week 8. Pain-related distress scale is from 0 (no pain) to 10 (worst pain).

  • Pain Duration [ Time Frame: at 9 weeks ] [ Designated as safety issue: No ]
    Pain duration in hours 0 to 24

Secondary Outcome Measures:
  • Ability to Engage in Activities of Daily Living (ADL) [ Time Frame: Baseline(Week 0) to week 8, Total time frame is 9 weeks. ] [ Designated as safety issue: No ]
    The Functional Assessment Screening Questionnaire (FASQ) scale is used, scored at baseline and at weeks 2, 4, 6, 8. The FASQ consists of 15 questions about ability to perform ADL with minimum score of 1 (easy to perform) to a maximum score of 5 (N/A, meaning someone else performs this activity for the patient or else the patient chooses not to do it). A summary mean score is generated with a minimum score of 1 and a maximum score of 5.

  • Interference in Daily Life Due to Pain [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
    Patients in each arm will each have 5 measures on the Brief Pain Inventory (BPI) scale: baseline + weeks 2, 4, 6, 8. The BPI consists of 7 questions about interference of pain in daily life, answered on a scale of 0 (does not interfere) to 10 (completely interferes). The summary score is the average from the 7 questions, with higher score indicating greater interference due to pain.

  • Mood Disturbance [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
    Patients in each arm will each have 5 measures on the Profile of Mood States-Short Form (POMS-SF): baseline + weeks 2, 4, 6, 8. The POMS-SF consists of 37 questions, querying 6 mood states (anxiety, depression, anger, confusion, fatigue, and vigor), with responses on a scale from 0 (not at all) to 4 (extremely). To generate a summary score, questions on vigor state are first recoded to reverse the scale, so that higher summary scores consistently indicate greater mood disturbance.

  • Quality of Life [ Time Frame: 9 weeks ] [ Designated as safety issue: No ]
    Each patient in each arm is scored on the Functional Assessment of Cancer Therapy-General (FACT-G) at baseline + week 8 with 4 related sub-scales (physical, social/family, emotional, functional well-being. To generate sub-scale scores, physical and emotional items are reverse coded & items are then summed, such that higher values indicate better quality of life. Thus, each sub-scale score ranges from 0 (not at all, worse outcome) to 4 (very much, better outcome) with a minimum total score of 0 (worst quality of life) to a maximum of 16 (good quality of life).

Enrollment: 98
Study Start Date: May 2005
Study Completion Date: May 2010
Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Standard of Care
Standard pain control drugs.
Other: educational intervention
Participants will be educated on pain management.
Other: questionnaire administration
Participants will be given questionnaires to complete.
Experimental: Opioid Titration
Pain will be Monitored and Medication Titrated
Other: educational intervention
Participants will be educated on pain management.
Other: Titrated pain management
Pain will be Monitored and Medication Titrated
Other: questionnaire administration
Participants will be given questionnaires to complete.

Detailed Description:


  • To examine the effect of an opioid titration order sheet on pain outcomes.
  • To examine the effect of an opioid titration order sheet on secondary outcomes of function, mood, and quality of life.

OUTLINE: This is a multicenter study. Participating centers are randomized to 1 of 2 treatment arms.

  • Arm I (usual care): After completion of baseline assessments, patients undergo a standardized pain education program over approximately 15 minutes. The program consists of standard written materials about communicating pain to providers, opioids and side effect management, as well as a tailored discussion about patient concerns and specific information about prescribed opioid medications. Patients are also instructed in the use of the daily pain diary. Patients are then discharged from the clinic with instructions to contact the treating physician (through standard procedures) for problems with pain or side effects. The study staff conducts weekly telephone interviews to prevent changes in patient pain management practice. The treating physician continues to manage pain in their usual manner.
  • Arm II (opioid titration order sheet): After completion of baseline assessments, patients undergo the standardized pain education program and are instructed in the use of the daily pain diary as described in arm I. The treating physician signs an Opioid Titration Order Sheet (OTOS) providing a baseline dose and schedule. The OTOS is faxed to study staff and verified. Patients are then discharged from the clinic with instructions to contact the research nurse for problems with pain or side effects. The treating physician also contacts the study staff if he/she is made aware of any problems pertaining to the patient's pain control. The research nurse, in consultation with study physician, manages pain according to the OTOS and manages opioid side effects using standing orders. Referral to the treating physician is made as needed.

Patients' pain is managed on study for 8 weeks in the absence of unacceptable toxicity, pain crisis, or new site of pain.

Patients complete a demographic questionnaire at baseline and other questionnaires at 2, 4, and 6 weeks (over the telephone) and at 8 weeks (at site or by telephone), including the Functional Assessment Screening Questionnaire (FASQ), the Brief Pain Inventory-Interference (PPI-I), The Profile of Mood States-Short Form (POMS-SF), and the Quality of life (FACT-G) questionnaire. Patients also complete a pain diary recording daily measures of pain dimensions, analgesic use (i.e., fixed dose opioids, rescue doses, and non-opioids), adjuvant medications, and side effects that prevented the patient from taking medications. Data in the pain diary is transcribed over the telephone on a weekly basis.

Clinical data, including the type of cancer, stage of disease, time since diagnosis, current treatment for cancer, type of pain, time since onset of pain, and time of first opioid prescription, as well as information regarding analgesics (opioid and non-opioid), adjuvant medications, and medications to manage side effects prescribed during the study is collected from patients' medical records. Anticancer and palliative treatment received during the study is monitored via treating physician records.

The physician charts are reviewed after study completion to determine whether pain, treatment, and response are adequately documented and treated. The documentation in the physician charts is compared to the documentation obtained by the study staff during the study.


Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No


  • Histologically confirmed carcinoma
  • Cancer-related pain requiring fixed-dose opioid therapy

    • Has received ≥ 1 week of fixed-dose opioid therapy AND meets any of the following criteria:

      • Inadequate pain control as defined by the patient
      • Requires 2 or more rescue doses per day
      • Requires adjustments in pain regimen (either fixed or breakthrough dosing)
  • No pain crisis that requires hospitalization or immediate anesthetic or neurosurgical intervention
  • No predominantly neuropathic pain (e.g., peripheral neuropathy) as assessed by the treating physician


  • ECOG performance status 0-2
  • ANC > 1,500/mm³
  • Platelet count > 100,000/mm³
  • Serum bilirubin < 1.5 mg/dL
  • Serum creatinine < 2.5 mg/dL
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Nutritional, pulmonary, and cardiac status must be considered adequate to tolerate the proposed study therapy
  • Must be available for active follow-up
  • No documented active psychiatric disorder (i.e., psychosis or major depression) that would preclude informed consent or the patient's ability to comply with study procedures
  • No significant infection
  • No concerns about compliance with medication regimens or medical follow-up
  • No excessive alcohol use


  • See Disease Characteristics
  • Concurrent chemotherapy or radiotherapy allowed
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00666211

United States, Kentucky
Jennie Stuart Medical Center
Hopkinsville, Kentucky, United States, 44240
Mitchell Memorial Cancer Center at Owensboro Medical Health System
Owensboro, Kentucky, United States, 42303
United States, Tennessee
Erlanger Health System
Chattanooga, Tennessee, United States, 37403
Tennessee Plateau Oncology
Crossville, Tennessee, United States, 38555
Center for Biomedical Research
Knoxville, Tennessee, United States, 37909
The Jones Clinic
Memphis, Tennessee, United States, 38138
Meharry Medical College
Nashville, Tennessee, United States, 37208
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232-6838
Vanderbilt-Ingram Cancer Center - Cool Springs
Nashville, Tennessee, United States, 37064
Vanderbilt-Ingram Cancer Center at Franklin
Nashville, Tennessee, United States, 37064
Veterans Affairs Medical Center - Nashville
Nashville, Tennessee, United States, 37212
Sponsors and Collaborators
Vanderbilt-Ingram Cancer Center
Principal Investigator: Nancy Wells, DNSc, RN Vanderbilt-Ingram Cancer Center
  More Information

No publications provided

Responsible Party: Nancy Wells, Research Professor of Nursing; Director, VUMC Nursing; Researcher, Vanderbilt-Ingram Cancer Center Identifier: NCT00666211     History of Changes
Other Study ID Numbers: VICC SUPP 0424, P30CA068485, VU-VICC-SUPP-0424, VU-VICC-040410
Study First Received: April 23, 2008
Results First Received: October 21, 2011
Last Updated: August 4, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Vanderbilt-Ingram Cancer Center:
unspecified adult solid tumor, protocol specific
accelerated phase chronic myelogenous leukemia
acute undifferentiated leukemia
adult acute lymphoblastic leukemia in remission
adult acute myeloid leukemia in remission
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with t(15;17)(q22;q12)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with t(8;21)(q22;q22)
atypical chronic myeloid leukemia, BCR-ABL negative
blastic phase chronic myelogenous leukemia
chronic myelomonocytic leukemia
chronic phase chronic myelogenous leukemia
mast cell leukemia
meningeal chronic myelogenous leukemia
progressive hairy cell leukemia, initial treatment
prolymphocytic leukemia
recurrent adult acute lymphoblastic leukemia
recurrent adult acute myeloid leukemia
recurrent adult T-cell leukemia/lymphoma
refractory chronic lymphocytic leukemia
refractory hairy cell leukemia
relapsing chronic myelogenous leukemia
secondary acute myeloid leukemia
stage I adult T-cell leukemia/lymphoma
stage I chronic lymphocytic leukemia
stage II adult T-cell leukemia/lymphoma
stage II chronic lymphocytic leukemia

Additional relevant MeSH terms:
Central Nervous System Neoplasms
Lymphoproliferative Disorders
Multiple Myeloma
Myelodysplastic Syndromes
Myelodysplastic-Myeloproliferative Diseases
Myeloproliferative Disorders
Precancerous Conditions
Blood Protein Disorders
Bone Marrow Diseases
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Plasma Cell
Nervous System Diseases
Nervous System Neoplasms
Vascular Diseases processed this record on March 03, 2015