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Pregabalin in Preventing Acute Pain Syndrome in Patients Receiving Paclitaxel

Primary Purpose

Pain, Peripheral Neuropathy

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
pregabalin
placebo
questionnaire administration
Sponsored by
Academic and Community Cancer Research United
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Pain

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Cancer Center of Kansas
  • Essentia Health-Duluth CCOP
  • Mayo Clinic
  • Coborn Cancer Center at Saint Cloud Hospital
  • Missouri Valley Cancer Consortium
  • Marshfield Clinic - Marshfield Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Arm I (pain therapy)

Arm II (placebo)

Arm Description

Patients receive pregabalin PO BID, beginning on the first night of chemotherapy, for 12 weeks and then QD for 1 week.

Patients receive placebo PO BID, beginning on the first night of chemotherapy, for 12 weeks and then QD for 1 week.

Outcomes

Primary Outcome Measures

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).
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).

Secondary Outcome Measures

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.
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.
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.
The Percentage of Patients Taking Opioid Medications
The percentage of patients taking opioid medications are reported below by arm.
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.
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).
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.
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.
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.

Full Information

First Posted
March 9, 2012
Last Updated
April 4, 2018
Sponsor
Academic and Community Cancer Research United
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1. Study Identification

Unique Protocol Identification Number
NCT01637077
Brief Title
Pregabalin in Preventing Acute Pain Syndrome in Patients Receiving Paclitaxel
Official Title
RC11C3, Pilot Placebo-controlled Evaluation of Pregabalin as a Means to Prevent the Paclitaxel-Associated Acute Pain Syndrome
Study Type
Interventional

2. Study Status

Record Verification Date
April 2018
Overall Recruitment Status
Completed
Study Start Date
January 2012 (undefined)
Primary Completion Date
November 2013 (Actual)
Study Completion Date
April 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Academic and Community Cancer Research United

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pain, Peripheral Neuropathy

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
46 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm I (pain therapy)
Arm Type
Experimental
Arm Description
Patients receive pregabalin PO BID, beginning on the first night of chemotherapy, for 12 weeks and then QD for 1 week.
Arm Title
Arm II (placebo)
Arm Type
Placebo Comparator
Arm Description
Patients receive placebo PO BID, beginning on the first night of chemotherapy, for 12 weeks and then QD for 1 week.
Intervention Type
Drug
Intervention Name(s)
pregabalin
Other Intervention Name(s)
3-Isobutyl GABA, CI-1008, Lyrica, PD-144723
Intervention Description
Given PO
Intervention Type
Drug
Intervention Name(s)
placebo
Other Intervention Name(s)
PLCB
Intervention Description
Given PO
Intervention Type
Other
Intervention Name(s)
questionnaire administration
Intervention Description
Ancillary studies
Primary Outcome Measure Information:
Title
Worst of the Pain Scores for the Week Following the First Cycle of Paclitaxel Administration, Paclitaxel-associated Acute Pain Syndrome (P-APS) Pain Score
Description
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).
Time Frame
From treatment initiation to 6 days following treatment initiation; up to 7 days
Title
Maximum of the Average Pain Scores (Item 3, Appendix IV) Over the Period From Treatment Initiation to Day 7 (for Cycle 1).
Description
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).
Time Frame
From treatment initiation to 6 days following treatment initiation; up to 7 days
Secondary Outcome Measure Information:
Title
Area Under the Curve Per Assessment (aAUCpa) of Worst, Average and Least Pain (Items 1-3 Appendix IV) for the First Cycle of Treatment.
Description
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.
Time Frame
From treatment initiation to 6 days following treatment initiation; up to 7 days
Title
Percentage of Participants With Grade 3 or Higher Adverse Events Considered At Least Possibly Related to Treatment
Description
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.
Time Frame
Baseline, day 8 prior to each paclitaxel course, and then every 30 days for 6 months after completion of study treatment
Title
The Percentage of Patients Who Use Non-prescription Pain Medications
Description
The percentage of patients who use non-prescription pain medications are reported by arm below.
Time Frame
From treatment initiation to 6 months.
Title
The Percentage of Patients Taking Opioid Medications
Description
The percentage of patients taking opioid medications are reported below by arm.
Time Frame
From treatment initiation to 6 months.
Title
The Percentage of Patients Who Report the Development of New Aches/Pains That They Attribute to Paclitaxel
Description
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.
Time Frame
From treatment initiation to 6 days following treatment initiation; up to 7 days
Title
The Worst Pain Reported at the End of the Week for the Overall Week (Item 2 Appendix V)
Description
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).
Time Frame
From treatment initiation to 6 days following treatment initiation; up to 7 days
Title
The Percentage of Patients Who Report, at Week's End, Using Non-prescription Pain Medications
Description
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.
Time Frame
From treatment initiation to 6 days following treatment initiation; up to 7 days
Title
The Percentage of Patients Who Report, at Week's End, Using Opioids
Description
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.
Time Frame
From treatment initiation to 6 days following treatment initiation; up to 7 days
Title
Area Under the Curve (AUC) of EORTC Sensory, Autonomic, and Motor Neuropathy Subscales
Description
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.
Time Frame
From treatment initiation to 6 months.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Charles Loprinzi
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cancer Center of Kansas
City
Wichita
State/Province
Kansas
ZIP/Postal Code
67214
Country
United States
Facility Name
Essentia Health-Duluth CCOP
City
Duluth
State/Province
Minnesota
ZIP/Postal Code
55805
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Coborn Cancer Center at Saint Cloud Hospital
City
Saint Cloud
State/Province
Minnesota
ZIP/Postal Code
56303
Country
United States
Facility Name
Missouri Valley Cancer Consortium
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68106
Country
United States
Facility Name
Marshfield Clinic - Marshfield Center
City
Marshfield
State/Province
Wisconsin
ZIP/Postal Code
54449
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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Pregabalin in Preventing Acute Pain Syndrome in Patients Receiving Paclitaxel

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