Pregabalin in Preventing Acute Pain Syndrome in Patients Receiving Paclitaxel

• ClinicalTrials.gov Identifier: NCT01637077
• Recruitment Status: Completed
• First Posted: July 10, 2012
• Results First Posted: April 6, 2018
• Last Update Posted: April 6, 2018
• Sponsor: Academic and Community Cancer Research United
• Information provided by (Responsible Party): Academic and Community Cancer Research United

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.

Condition or disease	Intervention/treatment	Phase
Pain; Peripheral Neuropathy	Drug: pregabalin; Drug: placebo; Other: questionnaire administration	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 46 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Supportive Care
• Official Title: RC11C3, Pilot Placebo-controlled Evaluation of Pregabalin as a Means to Prevent the Paclitaxel-Associated Acute Pain Syndrome
• Study Start Date: January 2012
• Actual Primary Completion Date: November 2013
• Actual Study Completion Date: April 2016

Arms and Interventions

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.	Drug: pregabalin; Given PO; Other Names: 3-Isobutyl GABA; CI-1008; Lyrica; PD-144723; Other: questionnaire administration; Ancillary studies
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.	Drug: placebo; Given PO; Other Name: PLCB; Other: questionnaire administration; Ancillary studies

Outcome Measures

Primary Outcome Measures :

1. Worst of the Pain Scores for the Week Following the First Cycle of Paclitaxel Administration, Paclitaxel-associated Acute Pain Syndrome (P-APS) Pain Score [ Time Frame: 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).
2. Maximum of the Average Pain Scores (Item 3, Appendix IV) Over the Period From Treatment Initiation to Day 7 (for Cycle 1). [ Time Frame: 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 Outcome Measures :

1. Area Under the Curve Per Assessment (aAUCpa) of Worst, Average and Least Pain (Items 1-3 Appendix IV) for the First Cycle of Treatment. [ Time Frame: 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.
2. Percentage of Participants With Grade 3 or Higher Adverse Events Considered At Least Possibly Related to Treatment [ Time Frame: 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.
3. The Percentage of Patients Who Use Non-prescription Pain Medications [ Time Frame: From treatment initiation to 6 months. ]
   The percentage of patients who use non-prescription pain medications are reported by arm below.
4. The Percentage of Patients Taking Opioid Medications [ Time Frame: From treatment initiation to 6 months. ]
   The percentage of patients taking opioid medications are reported below by arm.
5. The Percentage of Patients Who Report the Development of New Aches/Pains That They Attribute to Paclitaxel [ Time Frame: 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.
6. The Worst Pain Reported at the End of the Week for the Overall Week (Item 2 Appendix V) [ Time Frame: 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).
7. The Percentage of Patients Who Report, at Week's End, Using Non-prescription Pain Medications [ Time Frame: 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.
8. The Percentage of Patients Who Report, at Week's End, Using Opioids [ Time Frame: 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.
9. Area Under the Curve (AUC) of EORTC Sensory, Autonomic, and Motor Neuropathy Subscales [ Time Frame: 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.

Eligibility Criteria

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

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

Contacts and Locations

Locations

United States, Kansas

Cancer Center of Kansas

Wichita, Kansas, United States, 67214

United States, Minnesota

Essentia Health-Duluth CCOP

Duluth, Minnesota, United States, 55805

Mayo Clinic

Rochester, Minnesota, United States, 55905

Coborn Cancer Center at Saint Cloud Hospital

Saint Cloud, Minnesota, United States, 56303

United States, Nebraska

Missouri Valley Cancer Consortium

Omaha, Nebraska, United States, 68106

United States, Wisconsin

Marshfield Clinic - Marshfield Center

Marshfield, Wisconsin, United States, 54449

Sponsors and Collaborators

Academic and Community Cancer Research United

Investigators

• Principal Investigator: Charles Loprinzi; Mayo Clinic

More Information

• Responsible Party: Academic and Community Cancer Research United
• ClinicalTrials.gov Identifier: NCT01637077
• Obsolete Identifiers: NCT02166385
• Other Study ID Numbers: RC11C3; NCI-2011-03646 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
• First Posted: July 10, 2012
• Results First Posted: April 6, 2018
• Last Update Posted: April 6, 2018
• Last Verified: April 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

Additional relevant MeSH terms:

Peripheral Nervous System Diseases; Acute Pain; Neuromuscular Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Pregabalin; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anticonvulsants; Calcium Channel Blockers; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Calcium-Regulating Hormones and Agents; Anti-Anxiety Agents; Tranquilizing Agents; Central Nervous System Depressants; Psychotropic Drugs