Trial of Pregabalin for Granulocyte Colony-stimulating Factor (GCSF)-Induced Bone Pain
Condition: Breast Cancer; Lymphoma; Pain
Intervention: Pregabalin; Placebo
Intervention description: 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.; 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.
Intervention MeSH terms: Pregabalin
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
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
Enrollment: 11.0
Sex: All
Minimum age: 18 Years
Maximum age: 99 Years
Healthy volunteers: No
Keywords: Pregabalin; Bone pain; Pegfilgrastim; Supportive care; prevention

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.
    

Eligibility 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.