Pain, Peripheral Neuropathy
Conditions
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.
Interventions
DRUGpregabalin
Given PO
DRUGplacebo
Given PO
OTHERquestionnaire administration
Ancillary studies
Sponsors
Academic and Community Cancer Research United
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Worst of the Pain Scores for the Week Following the First Cycle of Paclitaxel Administration, Paclitaxel-associated Acute Pain Syndrome (P-APS) Pain Score | From treatment initiation to 6 days following treatment initiation; up to 7 days | 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). | From treatment initiation to 6 days following treatment initiation; up to 7 days | 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
| Measure | Time frame | Description |
|---|---|---|
| The Percentage of Patients Who Use Non-prescription Pain Medications | From treatment initiation to 6 months. | The percentage of patients who use non-prescription pain medications are reported by arm below. |
| The Percentage of Patients Taking Opioid Medications | From treatment initiation to 6 months. | 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 | From treatment initiation to 6 days following treatment initiation; up to 7 days | 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. |
| Area Under the Curve Per Assessment (aAUCpa) of Worst, Average and Least Pain (Items 1-3 Appendix IV) for the First Cycle of Treatment. | From treatment initiation to 6 days following treatment initiation; up to 7 days | 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. |
| The Percentage of Patients Who Report, at Week's End, Using Non-prescription Pain Medications | 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 (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 | 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 (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 | From treatment initiation to 6 months. | 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. |
| The Worst Pain Reported at the End of the Week for the Overall Week (Item 2 Appendix V) | 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 (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). |
| Percentage of Participants With Grade 3 or Higher Adverse Events Considered At Least Possibly Related to Treatment | Baseline, day 8 prior to each paclitaxel course, and then every 30 days for 6 months after completion of study 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm I (Pregabalin) Patients receive pregabalin (75 mg (one capsule)) PO BID, beginning on the first night of chemotherapy, for 12 weeks and then QD for 1 week. | 19 |
| Arm II (Placebo) Patients receive placebo (one capsule) PO BID, beginning on the first night of chemotherapy, for 12 weeks and then QD for 1 week. | 22 |
| Total | 41 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Cancel | 1 | 1 |
| Overall Study | No cycle 1 questionnaire data | 2 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Arm I (Pregabalin) | Arm II (Placebo) | Total |
|---|---|---|---|
| Age, Continuous | 54.2 years STANDARD_DEVIATION 12.9 | 53.2 years STANDARD_DEVIATION 14.3 | 53.7 years STANDARD_DEVIATION 13.5 |
| Region of Enrollment United States | 19 Participants | 22 Participants | 41 Participants |
| Sex: Female, Male Female | 19 Participants | 22 Participants | 41 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 21 | 0 / 22 |
| other Total, other adverse events | 15 / 21 | 21 / 22 |
| serious Total, serious adverse events | 1 / 21 | 1 / 22 |
Outcome results
Primary
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).
Time frame: From treatment initiation to 6 days following treatment initiation; up to 7 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm I (Pregabalin) | Maximum of the Average Pain Scores (Item 3, Appendix IV) Over the Period From Treatment Initiation to Day 7 (for Cycle 1). | 2.6 units on a scale | Standard Deviation 2.2 |
| Arm II (Placebo) | Maximum of the Average Pain Scores (Item 3, Appendix IV) Over the Period From Treatment Initiation to Day 7 (for Cycle 1). | 2.2 units on a scale | Standard Deviation 2.6 |
p-value: 0.48Kruskal-Wallis
Primary
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).
Time frame: From treatment initiation to 6 days following treatment initiation; up to 7 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm I (Pregabalin) | Worst of the Pain Scores for the Week Following the First Cycle of Paclitaxel Administration, Paclitaxel-associated Acute Pain Syndrome (P-APS) Pain Score | 2.6 units on a scale | Standard Deviation 2.5 |
| Arm II (Placebo) | Worst of the Pain Scores for the Week Following the First Cycle of Paclitaxel Administration, Paclitaxel-associated Acute Pain Syndrome (P-APS) Pain Score | 3.2 units on a scale | Standard Deviation 3 |
p-value: 0.56Kruskal-Wallis
Secondary
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.
Time frame: From treatment initiation to 6 months.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm I (Pregabalin) | Area Under the Curve (AUC) of EORTC Sensory, Autonomic, and Motor Neuropathy Subscales | Sensory | 88.4 average(subscale value*assessment) | Standard Deviation 12.5 |
| Arm I (Pregabalin) | Area Under the Curve (AUC) of EORTC Sensory, Autonomic, and Motor Neuropathy Subscales | Autonomic | 88.4 average(subscale value*assessment) | Standard Deviation 17.6 |
| Arm I (Pregabalin) | Area Under the Curve (AUC) of EORTC Sensory, Autonomic, and Motor Neuropathy Subscales | Motor | 92.0 average(subscale value*assessment) | Standard Deviation 11 |
| Arm II (Placebo) | Area Under the Curve (AUC) of EORTC Sensory, Autonomic, and Motor Neuropathy Subscales | Sensory | 84.5 average(subscale value*assessment) | Standard Deviation 16.7 |
| Arm II (Placebo) | Area Under the Curve (AUC) of EORTC Sensory, Autonomic, and Motor Neuropathy Subscales | Autonomic | 88.6 average(subscale value*assessment) | Standard Deviation 15.8 |
| Arm II (Placebo) | Area Under the Curve (AUC) of EORTC Sensory, Autonomic, and Motor Neuropathy Subscales | Motor | 90.2 average(subscale value*assessment) | Standard Deviation 10.7 |
Comparison: Sensory neuropathyp-value: 0.46Kruskal-Wallis
Comparison: Autonomic neuropathyp-value: 0.86Kruskal-Wallis
Comparison: Motor neuropathyp-value: 0.4Kruskal-Wallis
Secondary
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.
Time frame: From treatment initiation to 6 days following treatment initiation; up to 7 days
Population: The number analyzed for average pain over the past 24 hours differs from the overall number analyzed due to missing data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm I (Pregabalin) | Area Under the Curve Per Assessment (aAUCpa) of Worst, Average and Least Pain (Items 1-3 Appendix IV) for the First Cycle of Treatment. | Worst pain over the past 24 hours | 80.7 average(subscale value*assessment) | Standard Deviation 22.3 |
| Arm I (Pregabalin) | 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 pain over the past 24 hours | 82.8 average(subscale value*assessment) | Standard Deviation 20.2 |
| Arm I (Pregabalin) | Area Under the Curve Per Assessment (aAUCpa) of Worst, Average and Least Pain (Items 1-3 Appendix IV) for the First Cycle of Treatment. | Least pain over the past 24 hours | 82.6 average(subscale value*assessment) | Standard Deviation 23 |
| Arm II (Placebo) | Area Under the Curve Per Assessment (aAUCpa) of Worst, Average and Least Pain (Items 1-3 Appendix IV) for the First Cycle of Treatment. | Worst pain over the past 24 hours | 82.6 average(subscale value*assessment) | Standard Deviation 24 |
| Arm II (Placebo) | 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 pain over the past 24 hours | 86.8 average(subscale value*assessment) | Standard Deviation 19.7 |
| Arm II (Placebo) | Area Under the Curve Per Assessment (aAUCpa) of Worst, Average and Least Pain (Items 1-3 Appendix IV) for the First Cycle of Treatment. | Least pain over the past 24 hours | 91.3 average(subscale value*assessment) | Standard Deviation 14.8 |
Comparison: Worst pain over the past 24 hoursp-value: 0.62Kruskal-Wallis
Comparison: Average pain over the past 24 hoursp-value: 0.22Kruskal-Wallis
Comparison: Least pain over the past 24 hoursp-value: 0.07Kruskal-Wallis
Secondary
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.
Time frame: Baseline, day 8 prior to each paclitaxel course, and then every 30 days for 6 months after completion of study treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm I (Pregabalin) | Percentage of Participants With Grade 3 or Higher Adverse Events Considered At Least Possibly Related to Treatment | 2.2 percentage of patients |
| Arm II (Placebo) | Percentage of Participants With Grade 3 or Higher Adverse Events Considered At Least Possibly Related to Treatment | 0 percentage of patients |
Secondary
The Percentage of Patients Taking Opioid Medications
The percentage of patients taking opioid medications are reported below by arm.
Time frame: From treatment initiation to 6 months.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm I (Pregabalin) | The Percentage of Patients Taking Opioid Medications | 15.8 percentage of patients |
| Arm II (Placebo) | The Percentage of Patients Taking Opioid Medications | 18.2 percentage of patients |
p-value: 0.84Chi-squared
Secondary
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.
Time frame: From treatment initiation to 6 days following treatment initiation; up to 7 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm I (Pregabalin) | The Percentage of Patients Who Report, at Week's End, Using Non-prescription Pain Medications | 66.7 percentage of patients |
| Arm II (Placebo) | The Percentage of Patients Who Report, at Week's End, Using Non-prescription Pain Medications | 60. percentage of patients |
p-value: 0.78Chi-squared
Secondary
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.
Time frame: From treatment initiation to 6 days following treatment initiation; up to 7 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm I (Pregabalin) | The Percentage of Patients Who Report, at Week's End, Using Opioids | 0 percentage of patients |
| Arm II (Placebo) | The Percentage of Patients Who Report, at Week's End, Using Opioids | 26.7 percentage of patients |
p-value: 0.16Chi-squared
Secondary
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.
Time frame: From treatment initiation to 6 days following treatment initiation; up to 7 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm I (Pregabalin) | The Percentage of Patients Who Report the Development of New Aches/Pains That They Attribute to Paclitaxel | 23.5 percentage of patients |
| Arm II (Placebo) | The Percentage of Patients Who Report the Development of New Aches/Pains That They Attribute to Paclitaxel | 59.1 percentage of patients |
p-value: 0.03Chi-squared
Secondary
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.
Time frame: From treatment initiation to 6 months.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm I (Pregabalin) | The Percentage of Patients Who Use Non-prescription Pain Medications | 52.6 percentage of patients |
| Arm II (Placebo) | The Percentage of Patients Who Use Non-prescription Pain Medications | 50 percentage of patients |
p-value: 0.87Chi-squared
Secondary
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).
Time frame: From treatment initiation to 6 days following treatment initiation; up to 7 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm I (Pregabalin) | The Worst Pain Reported at the End of the Week for the Overall Week (Item 2 Appendix V) | 2.4 units on a scale | Standard Deviation 2.1 |
| Arm II (Placebo) | The Worst Pain Reported at the End of the Week for the Overall Week (Item 2 Appendix V) | 4.7 units on a scale | Standard Deviation 3.2 |
p-value: 0.12Kruskal-Wallis