Pregabalin in Preventing Acute Pain Syndrome in Patients Receiving Paclitaxel

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Pain, Peripheral Neuropathy

Intervention / Treatment
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* Drug: pregabalin
* Drug: placebo
* Other: questionnaire administration


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (pain therapy)<br>Patients receive pregabalin PO BID, beginning on the first night of chemotherapy, for 12 weeks and then QD for 1 week. | Drug: pregabalin<br>* Given PO<br>* Other names: PD-144723;Other: questionnaire administration<br>* Ancillary studies<br>|
| Placebo Comparator: Arm II (placebo)<br>Patients receive placebo PO BID, beginning on the first night of chemotherapy, for 12 weeks and then QD for 1 week. | Drug: placebo<br>* Given PO<br>* Other names: PLCB;Other: questionnaire administration<br>* Ancillary studies<br>|

What is the study measuring?
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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. |