Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Trial of Pregabalin for Granulocyte Colony-stimulating Factor (GCSF)-Induced Bone Pain

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03407430
Recruitment Status : Terminated (Low patient accrual)
First Posted : January 23, 2018
Results First Posted : June 25, 2018
Last Update Posted : June 25, 2018
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
UNC Lineberger Comprehensive Cancer Center

Brief Summary:

Purpose:

To evaluate the preventative effects of pregabalin on pegfilgrastim-induced bone pain in cycle 1. Because granulocyte colony stimulating factor (G-CSF) receptors are found at nerve endings which modulate the pain signal, blocking this with pregabalin is theorized to prevent the occurrence of this adverse effect.

Participants:

Patients will be at least 18 years of age with either a diagnosis of a non-myeloid hematologic malignancy scheduled to initiate a cycle of chemotherapy that requires prophylactic use of a G-CSF, or with a diagnosis of breast cancer scheduled to initiate dose-dense doxorubicin/cyclophosphamide chemotherapy or docetaxel/cyclophosphamide that requires prophylactic use of a G-CSF.

Procedures (methods):

This is a randomized (1:1), single center, placebo-controlled, double blind, crossover phase II study. The primary objective is to compare the proportion of patients who have an increase in pain score of ≥3 from baseline in cycle 1 between Arm A (pregabalin) and Arm B (placebo). In consultation with the treating physician, the PI will determine what day pegfilgrastim will be initiated in each eligible, consented patient. Pregabalin or placebo will begin 4 days prior to pegfilgrastim administration, and continue for 7 additional days starting the day of pegfilgrastim administration.


Condition or disease Intervention/treatment Phase
Breast Cancer Lymphoma Pain Drug: Pregabalin Drug: Placebo Phase 2

  Show Detailed Description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 11 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: placebo-controlled, double blind, randomized crossover trial
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Double-blind
Primary Purpose: Prevention
Official Title: A Phase II, Placebo-controlled, Double-blind, Randomized Crossover Trial of Pregabalin for the Prophylaxis of Pegfilgrastim-induced Bone Pain
Actual Study Start Date : January 27, 2016
Actual Primary Completion Date : June 3, 2017
Actual Study Completion Date : July 20, 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Pregabalin, then Placebo

Pregabalin in cycle 1; placebo in cycle 2.

Pregabalin or matching placebo will be administered at 75 mg twice a day (BID) for 4 days, to patients receiving pegfilgrastim for hematologic malignancies or breast cancer patients on myelosuppressive chemotherapy . Starting the day of pegfilgrastim, the dose of study medication will be increased to 150 mg PO BID provided the patient is tolerating the lower dose (ie, they are not experiencing any pregabalin associated toxicities >Grade 1). This will be determined by the research team on the day of pegfilgrastim administration.

Drug: Pregabalin
During the first chemotherapy cycle, the patient will receive pregabalin 75mg (1 capsule) BID x 4 days before pegfilgrastim 6mg subcutaneous (SC) x1; then pregabalin 150mg (2 capsules) BID x 7 days. During the second chemotherapy cycle, the patient will receive placebo in the same dosing scheme.
Other Name: Pregabalin/Placebo

Experimental: Placebo, then Pregabalin

Placebo in cycle 1; pregabalin in cycle 2.

Pregabalin or matching placebo will be administered at 75 mg BID for 4 days, to patients receiving pegfilgrastim for hematologic malignancies or breast cancer patients on myelosuppressive chemotherapy . Starting the day of pegfilgrastim, the dose of study medication will be increased to 150 mg PO BID provided the patient is tolerating the lower dose (ie, they are not experiencing any pregabalin associated toxicities >Grade 1). This will be determined by the research team on the day of pegfilgrastim administration.

Drug: Placebo
During the first chemotherapy cycle, the patient will receive placebo (1 capsule) BID x 4 days before pegfilgrastim 6mg SC x1; then placebo (2 capsules) BID x 7 days. During the second chemotherapy cycle, the patient will receive pregabalin in the same dosing scheme.
Other Name: Placebo/Pregabalin




Primary Outcome Measures :
  1. Number of Patients Who Have an Increase in Pain Score of ≥ 3 From Baseline Through the End of Study Medication in Cycle 1 [ Time Frame: Up to 12 weeks ]

    Compare the proportion of patients who have an increase in pain score of ≥ 3 from baseline through the end of study medication in cycle 1 between Arm A and Arm B.

    The ten-point numerical scale is scored from 0 to 10. They will use this scale to rate their pain (and separately bone/joint pain) with 0 signifying "no pain" and 10 signifying "the worst pain you can imagine."



Secondary Outcome Measures :
  1. Proportion of Patients Who Have an Increase in Pain Score of ≥ 3 From Baseline Between Pregabalin and Placebo Across the 2 Cycles [ Time Frame: Up to 12 weeks ]

    Compare the proportion of patients who have an increase in pain score of ≥ 3 from baseline between pregabalin and placebo across the 2 cycles.

    The ten-point numerical scale is scored from 0 to 10. They will use this scale to rate their pain (and separately bone/joint pain) with 0 signifying "no pain" and 10 signifying "the worst pain you can imagine."


  2. Proportion of Patients Who Have an Increase in Bone/Joint Pain Score of ≥ 3 From Baseline Through the End of Study Medication in Cycle 1 [ Time Frame: Up to 12 weeks ]

    Compare the proportion of patients who have an increase in bone/joint pain score of ≥ 3 from baseline through the end of study medication in cycle 1 between Arm A and Arm B.

    The ten-point numerical scale is scored from 0 to 10. They will use this scale to rate their pain (and separately bone/joint pain) with 0 signifying "no pain" and 10 signifying "the worst pain you can imagine."


  3. Number of Days of Breakthrough Analgesic Use Between Pregabalin and Placebo Across the 2 Cycles [ Time Frame: Up to 12 weeks ]

    Compare the number of days of breakthrough analgesic use between pregabalin and placebo within cycle 1 and across the 2 cycles.

    The number of days of breakthrough analgesic use (i.e additional pain medication being required) is evaluated based on participant-provided medication logs kept during study treatment. If additional pain medication outside of their normal pain control regimen was reported, this day counts as 1. The total days for each patient are then reported, with a total range from zero to 14 (for patients with breast cancer) or zero to 21 (for patients with a lymphoma).


  4. Proportion of Patients With Severe Pain Between Pregabalin and Placebo Across the 2 Cycles [ Time Frame: Up to 12 weeks ]

    Compare the proportion of patients with severe pain between pregabalin and placebo within cycle 1 and across the 2 cycles.

    The ten-point numerical scale is scored from 0 to 10. They will use this scale to rate their pain (and separately bone/joint pain) with 0 signifying "no pain" and 10 signifying "the worst pain you can imagine."


  5. Maximum Change in Pain Score From Baseline Between Pregabalin and Placebo Across the 2 Cycles [ Time Frame: Up to 12 weeks ]

    Compare the maximum change in pain score from baseline between pregabalin and placebo within cycle 1 and across the 2 cycles.

    The ten-point numerical scale is scored from 0 to 10. They will use this scale to rate their pain (and separately bone/joint pain) with 0 signifying "no pain" and 10 signifying "the worst pain you can imagine." Each patient will be assessed regularly, including: before therapeutic intervention (i.e. at consent/screening), first day of chemotherapy administration (during cycles 1 & 2), 4 days after pegfilgrastim administration (during cycles 1 & 2), and 8 days after pegfilgrastim administration (during cycles 1 & 2).


  6. Maximum Neuropathic Pain Score Between Pregabalin and Placebo Across the 2 Cycles [ Time Frame: Up to 12 weeks ]

    Compare the maximum neuropathic pain score between pregabalin and placebo within cycle 1 and across the 2 cycles.

    The "ID Pain" scale (also know as the "Identify Pain" scale) is a 6-item, participant-completed screening tool designed to help differentiate nociceptive and neuropathic pain. This pain score also helps to evaluate the presence/absence of neuropathic pain at a given point of time.

    1. Did the pain feel like pins and needles?
    2. Did the pain feel hot/burning?
    3. Did the pain feel numb?
    4. Did the pain feel like electrical shocks?
    5. Is the pain made worse with the touch of clothing or bed sheets?
    6. Is the pain limited to your joints?

    A "yes" response to questions 1-5 are scored as 1; for question 6, a "yes" is scored as −1. As such, higher scores (approaching 5) signify worse outcomes. The scale's total range for a patient is -1 to 5.


  7. Number of Subjects That Experienced a Grade 2 or Higher Adverse Events When Taking Pregabalin [ Time Frame: Up to 12 weeks ]
    CTCAE The NCI Common Terminology Criteria for Adverse Events is a descriptive terminology utilized for Adverse Event (AE) reporting. A grading (severity) scale is provided for each AE term. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥18 years
  • Diagnosis of a non-myeloid hematologic malignancy scheduled to initiate a cycle of chemotherapy that requires prophylactic use of a granulocyte colony-stimulating growth factor (based on the provider's discretion), provided the schedule of chemotherapy cycles allows the use of pegfilgrastim at a dose of 6 mg SC once per cycle OR Diagnosis of breast cancer scheduled to initiate dose-dense doxorubicin and cyclophosphamide (AC) chemotherapy or docetaxel and cyclophosphamide (TC) chemotherapy that requires prophylactic use of a granulocyte colony-stimulating growth factor, provided the schedule of chemotherapy cycles allows the use of pegfilgrastim, at a dose of 6 mg SC once per cycle; pegfilgrastim scheduled for 24 hours post chemotherapy.
  • Schedule of chemotherapy and pegfilgrastim initiation can accommodate initiation of pregabalin 4 days prior to pegfilgrastim dose.
  • Baseline pain scores <7 as measured via 10-point numerical scale for pain (see section 11.1); pain score and use of any non-opioid pain medication must be self-reported as stable (same dose and frequency) over the 7 days prior to screening; for opioids, patient must self-report the same dose and frequency over the 28 days prior to screening. Patients who are receiving peri-procedural short-acting analgesics will still be included as long as they are no longer receiving analgesics by D1 of chemotherapy.

Exclusion Criteria:

  • A history of (within one month) or current pregabalin use.
  • Baseline pain scores ≥7 as measured via 10-point numerical scale for pain (see section 11.1).
  • Unwilling to discontinue use of antihistamines from 7 days prior to D1 of study medication.
  • Creatinine clearance (CrCl) ≤60 ml/min (as measured via Cockcroft-Gault) based on serum creatinine measured as part of standard of care prior to administration of chemotherapy
  • Women of childbearing potential must have a negative serum pregnancy test prior to initiating therapy (note, this test should be standard of care prior to administration of chemotherapy).
  • Patient is unable or unwilling to abide by the study protocol or cooperate fully with the investigator.
  • Eligible and agrees to enroll into therapeutic trial ongoing at the Lineberger Comprehensive Cancer Center (LCCC) (i.e., the treatment trial will take precedence over LCCC1314).
  • Currently receiving therapeutic doses of anticoagulants (ie, prophylactic use of anticoagulants is allowed) due to possibility of dizziness and falls while on pregabalin.
  • Currently receiving aromatase inhibitors or agents targeted against Ph+ leukemias (i.e., imatinib, dasatinib, nilotinib, and ponatinib) or scheduled to start these drugs during cycle 1 of scheduled chemotherapy.
  • Presence of bone metastases.
  • History of angioedema.
  • History of a seizure disorder.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03407430


Locations
Layout table for location information
United States, North Carolina
North Carolina Cancer Hospital
Chapel Hill, North Carolina, United States, 27514
Sponsors and Collaborators
UNC Lineberger Comprehensive Cancer Center
Pfizer
Investigators
Layout table for investigator information
Principal Investigator: Benyam Muluneh, PharmD, CPP UNC Lineberger Comprehensive Cancer Center
  Study Documents (Full-Text)

Documents provided by UNC Lineberger Comprehensive Cancer Center:

Additional Information:
Publications:
Layout table for additonal information
Responsible Party: UNC Lineberger Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT03407430     History of Changes
Other Study ID Numbers: LCCC 1314
First Posted: January 23, 2018    Key Record Dates
Results First Posted: June 25, 2018
Last Update Posted: June 25, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Individual participant data (IPD) will not be shared and kept confidential.

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by UNC Lineberger Comprehensive Cancer Center:
Pregabalin
Bone pain
Pegfilgrastim
Supportive care
prevention

Additional relevant MeSH terms:
Layout table for MeSH terms
Pregabalin
Lenograstim
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
Immunologic Factors
Adjuvants, Immunologic