Pregabalin in Preventing Acute Pain Syndrome in Patients Receiving Paclitaxel

RC11C3, Pilot Placebo-controlled Evaluation of Pregabalin as a Means to Prevent the Paclitaxel-Associated Acute Pain Syndrome

This randomized pilot clinical trial studies pregabalin in preventing acute pain syndrome in patients receiving paclitaxel. Pregabalin may control the pain caused by cancer treatment.

Study Overview

• Status: Completed
• Conditions: Pain; Peripheral Neuropathy
• Intervention / Treatment: Other: questionnaire administration; Drug: placebo; Drug: pregabalin

Detailed Description

PRIMARY OBJECTIVES: I. To obtain pilot data regarding the possible effect of pregabalin on pain related to paclitaxel-associated acute pain syndrome (P-APS). SECONDARY OBJECTIVES: I. To obtain pilot data regarding the possible effect of pregabalin on paclitaxel-induced peripheral neuropathy. II. To obtain pilot data regarding the possible relative toxicities related to pregabalin therapy in this study situation. TERTIARY OBJECTIVES: I. To characterize neurological testing abnormalities that might occur with the P-APS, and to evaluate neurological testing abnormalities during the period of the longer-term chemotherapy-induced peripheral neuropathy (CIPN). II. To determine the PRO incidence and characteristics of, and change in, P-APS and paclitaxel induced more chronic CIPN over several cycles. These data will serve to confirm the results obtained in our previous natural history study N08C1. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive pregabalin orally (PO) twice daily (BID), beginning on the first night of chemotherapy, for 12 weeks and then once daily (QD) for 1 week. ARM II: Patients receive placebo PO BID, beginning on the first night of chemotherapy, for 12 weeks and then QD for 1 week. After completion of study treatment, patients are followed up every 30 days for 6 months.

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Wichita, Kansas, United States, 67214
      • Cancer Center of Kansas
  • Minnesota
    • Duluth, Minnesota, United States, 55805
      • Essentia Health-Duluth CCOP
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
    • Saint Cloud, Minnesota, United States, 56303
      • Coborn Cancer Center at Saint Cloud Hospital
  • Nebraska
    • Omaha, Nebraska, United States, 68106
      • Missouri Valley Cancer Consortium
  • Wisconsin
    • Marshfield, Wisconsin, United States, 54449
      • Marshfield Clinic - Marshfield Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age > or equal to 18 years
• Ability to complete questionnaires by themselves or with assistance Paclitaxel at a dose of 80 mg/m^2 given, in the adjuvant setting, every week for a planned course of 12 weeks without any other concurrent therapy
• Paclitaxel at a dose of 80 mg/m2 given, in the adjuvant (postoperative or neo-adjuvant) setting, every week for a planned course of 12 weeks without any other concurrent cytotoxic chemotherapy (trastuzumab and/or other antibody and/or small molecule treatment is allowed, except for PARP inhibitors).
• Life expectancy > 6 months
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Negative pregnancy test (serum or urine) done =< 7 days prior to registration, for women of childbearing potential only (per clinician discretion)

Exclusion Criteria:

• Pregnant women
• Nursing women
• Men or women of childbearing potential who are unwilling to employ adequate contraception since this study involves agents that have known genotoxic, mutagenic and teratogenic effects
• Previous diagnosis of diabetic or other peripheral neuropathy
• Current, planned or previous use, within last 6 months, of gabapentin or pregabalin
• History of allergic or other adverse reactions to gabapentin or pregabalin
• Significant renal insufficiency with a history of a creatinine clearance (CrCL) < 30ml/min
• Prior exposure to neurotoxic chemotherapy
• Seizure history
• Diagnosis of fibromyalgia
• Previous exposure to paclitaxel

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (pain therapy); Patients receive pregabalin PO BID, beginning on the first night of chemotherapy, for 12 weeks and then QD for 1 week.	Other: questionnaire administration; Ancillary studies; Drug: pregabalin; Given PO; Other Names: Lyrica; 3-Isobutyl GABA; CI-1008; PD-144723
Placebo Comparator: Arm II (placebo); Patients receive placebo PO BID, beginning on the first night of chemotherapy, for 12 weeks and then QD for 1 week.	Other: questionnaire administration; Ancillary studies; Drug: placebo; Given PO; Other Names: PLCB

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Worst of the Pain Scores for the Week Following the First Cycle of Paclitaxel Administration, Paclitaxel-associated Acute Pain Syndrome (P-APS) Pain Score	Worst of the pain scores for the week following the first cycle of paclitaxel administration, as measured by a question on the daily post-paclitaxel questionnaire. Worst pain over the first 6 days following treatment initiation. Higher scores represent more pain (0: No aches or pains -10: Aches or pains as bad as can be).	From treatment initiation to 6 days following treatment initiation; up to 7 days
Maximum of the Average Pain Scores (Item 3, Appendix IV) Over the Period From Treatment Initiation to Day 7 (for Cycle 1).	Maximum of average pain scores over 6 days following initiation of treatment. Average pain over the first 6 days following treatment initiation. Maximum of the average pain scores (item 3, appendix IV; "Please rate the same aches/pain by circling the ONE number that best describes your aches/pains on the AVERAGE in the last 24 hours.") over the period from treatment initiation to day 7 (for cycle 1). Higher scores represent more pain (0: No aches or pains -10: Aches or pains as bad as can be).	From treatment initiation to 6 days following treatment initiation; up to 7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Curve Per Assessment (aAUCpa) of Worst, Average and Least Pain (Items 1-3 Appendix IV) for the First Cycle of Treatment.	Average Area Under the Curve per assessment (aAUCpa) of worst, average, and least pain (items 1-3 app. IV; "Please rate any aches/pains that are NEW since your last dose of paclitaxel, and that you think might be related to your chemotherapy treatment by circling ONE number that best describes your aches/pains at its WORST in the last 24 hours.", "Please rate the same aches/pains by circling the ONE number that best describes your aches/pains at its LEAST in the last 24 hours.", "Please rate the same aches/pain by circling the ONE number that best describes your aches/pains on the AVERAGE in the last 24 hours.") for the first cycle of treatment. Scores are reported on a 0-100 scale, where 100=better outcome QOL. The aAUCpa is the average of each AUC between each sequential assessment from treatment-initiation to the day-6 assessment.	From treatment initiation to 6 days following treatment initiation; up to 7 days
Percentage of Participants With Grade 3 or Higher Adverse Events Considered At Least Possibly Related to Treatment	The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns within patient groups. In addition, we will review all adverse event data that is graded as 3, 4, or 5 and classified as either "unrelated" or "unlikely to be related" to study treatment in the event of an actual relationship developing. The overall toxicity rates (percentages) for grade 3 or higher adverse events considered at least possibly related to treatment are reported below.	Baseline, day 8 prior to each paclitaxel course, and then every 30 days for 6 months after completion of study treatment
The Percentage of Patients Who Use Non-prescription Pain Medications	The percentage of patients who use non-prescription pain medications are reported by arm below.	From treatment initiation to 6 months.
The Percentage of Patients Taking Opioid Medications	The percentage of patients taking opioid medications are reported below by arm.	From treatment initiation to 6 months.
The Percentage of Patients Who Report the Development of New Aches/Pains That They Attribute to Paclitaxel	The percentage of patients who report the development of new aches/pains that they attribute to paclitaxel in the first week of chemotherapy are reported by arm below.	From treatment initiation to 6 days following treatment initiation; up to 7 days
The Worst Pain Reported at the End of the Week for the Overall Week (Item 2 Appendix V)	The worst pain reported at the end of the week for the overall week ("New aches and pains at their worst over the past week") are reported below. This question was only supposed to be answered by patients who responded "yes" to the first question. Currently, all responses are included, regardless of whether the patient should've responded or not. The worst pain reported at the end of the week for the overall week (item 2 appendix V: "Please rate any aches/pains that you have by circling ONE number that best describes your aches/pains at its worst over the last week.") Higher scores represent more pain (0: No aches or pains -10: Aches or pains as bad as can be).	From treatment initiation to 6 days following treatment initiation; up to 7 days
The Percentage of Patients Who Report, at Week's End, Using Non-prescription Pain Medications	The percentage of patients who report, at week's end, using non-prescription pain medications ("Have you used non-prescription meds like aspirin, Tylenol, Motrin, Ibuprofen, or Advil over the past week?") are reported by arm below. This question was only supposed to be answered by patients who responded "yes" to the first question. Currently, all responses are included, regardless of whether the patient should've responded or not.	From treatment initiation to 6 days following treatment initiation; up to 7 days
The Percentage of Patients Who Report, at Week's End, Using Opioids	The percentage of patients who report, at week's end, using opioids ("Have you used opioids like codeine, oxycodone, or morphine for this pain over the past week?") are reported by arm below. This question was only supposed to be answered by patients who responded "yes" to the first question. Currently, all responses are included, regardless of whether the patient should've responded or not.	From treatment initiation to 6 days following treatment initiation; up to 7 days
Area Under the Curve (AUC) of EORTC Sensory, Autonomic, and Motor Neuropathy Subscales	Average Area Under the Curve per assessment (aAUCpa) of EORTC Chemotherapy-Induced Peripheral Neurophathy Module (EORTC QLQ-CIPN20) Sensory, Autonomic, and Motor Neuropathy Subscales. The EORTC CIPN20 scoring algorithm was used for the sensory (items 31-36, 39, 40 and 48), motor (items 37, 38, 41-45, 49), and autonomic (items 46, 47, 50) subscale scores on a 0-100 scale, with higher scores represent fewer symptoms (better QOL). The aAUCpa for each subscale is calculated as the average of each AUC between each sequential assessment from treatment-initiation to the 6-month assessment. For example; for each patient and each subscale, the subscale values at treatment-initiation and assessment-1 are used to calculate an Area Under the Curve (AUC) for that assessment time-period. Then these AUCs for all available assessment time-periods up to 6-months are averaged to yield the aAUCpa per patient per subcale.	From treatment initiation to 6 months.

Collaborators and Investigators

• Sponsor: Academic and Community Cancer Research United

Study record dates

Study Major Dates

• Study Start: January 1, 2012
• Primary Completion (Actual): November 1, 2013
• Study Completion (Actual): April 1, 2016

Study Registration Dates

• First Submitted: March 9, 2012
• First Submitted That Met QC Criteria: July 9, 2012
• First Posted (Estimate): July 10, 2012

Study Record Updates

• Last Update Posted (Actual): April 6, 2018
• Last Update Submitted That Met QC Criteria: April 4, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Pain; Neurologic Manifestations; Neuromuscular Diseases; Peripheral Nervous System Diseases; Acute Pain; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; Anti-Anxiety Agents; Anticonvulsants; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Pregabalin
• Other Study ID Numbers: RC11C3; NCI-2011-03646 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED