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

NCT03407430 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: LCCC 1314
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

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.

Conditions

Breast Cancer; Lymphoma; Pain

Keywords

Pregabalin; Bone pain; Pegfilgrastim; Supportive care; prevention

Outcome Measures

Primary Outcomes (1)

• Number of Patients Who Have an Increase in Pain Score of ≥ 3 From Baseline Through the End of Study Medication in Cycle 1

  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."

  Up to 12 weeks

Secondary Outcomes (7)

• Proportion of Patients Who Have an Increase in Pain Score of ≥ 3 From Baseline Between Pregabalin and Placebo Across the 2 Cycles

  Up to 12 weeks

• 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

  Up to 12 weeks

• Number of Days of Breakthrough Analgesic Use Between Pregabalin and Placebo Across the 2 Cycles

  Up to 12 weeks

• Proportion of Patients With Severe Pain Between Pregabalin and Placebo Across the 2 Cycles

  Up to 12 weeks

• Maximum Change in Pain Score From Baseline Between Pregabalin and Placebo Across the 2 Cycles

  Up to 12 weeks

Study Arms (2)

Pregabalin, then Placebo

EXPERIMENTAL

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

Placebo, then Pregabalin

EXPERIMENTAL

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

Interventions

Pregabalin DRUG

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.

Also known as: Pregabalin/Placebo

Pregabalin, then Placebo

Placebo DRUG

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.

Also known as: Placebo/Pregabalin

Placebo, then Pregabalin

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• UNC Lineberger Comprehensive Cancer Center: lead
• Pfizer: collaborator

Study Sites (1)

North Carolina Cancer Hospital

Chapel Hill, North Carolina, 27514, United States

Location

Related Publications (5)

• Amgen. Pegfilgrastim. Package Insert. Accessed June 9, 2013

  BACKGROUND

• Kirshner J, Hickock J, Hofman M. Pegfilgrastim-induced bone pain: Incidence, risk factors, and management in a community practice. Comm Onc 4:455-459, 2007.

  BACKGROUND

• Kirshner JJ, Heckler CE, Janelsins MC, Dakhil SR, Hopkins JO, Coles C, Morrow GR. Prevention of pegfilgrastim-induced bone pain: a phase III double-blind placebo-controlled randomized clinical trial of the university of rochester cancer center clinical community oncology program research base. J Clin Oncol. 2012 Jun 1;30(16):1974-9. doi: 10.1200/JCO.2011.37.8364. Epub 2012 Apr 16.

  PMID: 22508813 BACKGROUND

• Kubista E, Glaspy J, Holmes FA, Green MD, Hackett J, Neumann T; Pegfilgrastim Study Group. Bone pain associated with once-per-cycle pegfilgrastim is similar to daily filgrastim in patients with breast cancer. Clin Breast Cancer. 2003 Feb;3(6):391-8. doi: 10.3816/cbc.2003.n.003.

  PMID: 12636878 BACKGROUND

• Tassone DM, Boyce E, Guyer J, Nuzum D. Pregabalin: a novel gamma-aminobutyric acid analogue in the treatment of neuropathic pain, partial-onset seizures, and anxiety disorders. Clin Ther. 2007 Jan;29(1):26-48. doi: 10.1016/j.clinthera.2007.01.013.

  PMID: 17379045 BACKGROUND

Related Links

• University of North Carolina (UNC) Lineberger Comprehensive Cancer Center Clinical Trials

MeSH Terms

Conditions

Breast Neoplasms; Lymphoma; Pain

Interventions

Pregabalin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Limitations and Caveats

We were unable to achieve the target number of subject participants (target n=60; accrual n=11) needed to achieve target power and statistically reliable results.

Results Point of Contact

• Title: Dr. Benyam Muluneh
• Organization: University of North Carolina Medical Center

benyam.muluneh@unchealth.unc.edu

919-966-3213

Study Officials

• Benyam Muluneh, PharmD, CPP

  UNC Lineberger Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: placebo-controlled, double blind, randomized crossover trial

Study Record Dates

• First Submitted: January 2, 2018
• First Posted: January 23, 2018
• Study Start: January 27, 2016
• Primary Completion: June 3, 2017
• Study Completion: July 20, 2017
• Last Updated: June 26, 2018
• Results First Posted: June 26, 2018

Record last verified: 2018-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)