NCT03407430

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

Terminated Phase 2 Results posted Last updated 26 June 2018

What this trial tests

Phase 2 trial testing Pregabalin in Breast Cancer in 11 participants. Terminated before completion.

Timeline

27 January 2016

Primary endpoint
3 June 2017

20 July 2017

Quick facts

Lead sponsor	UNC Lineberger Comprehensive Cancer Center
Phase	Phase 2
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	crossover
Masking	quadruple
Primary purpose	prevention
Enrollment	11
Start date	27 January 2016
Primary completion	3 June 2017
Estimated completion	20 July 2017
Sites	1 location across United States

Drugs / interventions tested

• Pregabalin (Pregabalin) — full drug profile →
• Placebo

Conditions studied

• Breast Cancer — all drugs for Breast Cancer →
• Lymphoma — all drugs for Lymphoma →
• Pain — all drugs for Pain →

Sponsor

UNC Lineberger Comprehensive Cancer Center — full company profile →

Who can join

Adults 18 to 99, any sex, with Breast Cancer or Lymphoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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

Group	Value	95% CI
First Intervention = Pregabalin	0
First Intervention = Placebo	0

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

Group	Value	95% CI
First Intervention = Pregabalin	0
Second Intervention = Placebo	0.5
First Intervention = Placebo	0
Second Intervention = Pregabalin	0.333

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 Secondary · 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."

Group	Value	95% CI
First Intervention = Pregabalin	0
First Intervention = Placebo	0

Number of Days of Breakthrough Analgesic Use Between Pregabalin and Placebo Across the 2 Cycles Secondary · 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).

Group	Value	95% CI
First Intervention = Pregabalin	1.4	0 – 5
Second Intervention = Placebo	3.25	0 – 13
First Intervention = Placebo	0.67	0 – 1
Second Intervention = Pregabalin	0	0 – 0

Proportion of Patients With Severe Pain Between Pregabalin and Placebo Across the 2 Cycles Secondary · 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."

Group	Value	95% CI
First Intervention = Pregabalin	0.4
Second Intervention = Placebo	0.25
First Intervention = Placebo	0.67
Second Intervention = Pregabalin	0

Maximum Change in Pain Score From Baseline Between Pregabalin and Placebo Across the 2 Cycles Secondary · 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 p

Group	Value	95% CI
First Intervention = Pregabalin	0.4	0 – 2
Second Intervention = Placebo	2	0 – 4
First Intervention = Placebo	0	0 – 0
Second Intervention = Pregabalin	1.67	0 – 5

Maximum Neuropathic Pain Score Between Pregabalin and Placebo Across the 2 Cycles Secondary · 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

Group	Value	95% CI
First Intervention = Pregabalin	0.2	0 – 1
Second Intervention = Placebo	0.5	0 – 2
First Intervention = Placebo	0	0 – 0
Second Intervention = Pregabalin	0.33	0 – 1

Number of Subjects That Experienced a Grade 2 or Higher Adverse Events When Taking Pregabalin Secondary · 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;

Group	Value	95% CI
First Intervention = Pregabalin	0
Second Intervention = Pregabalin	0

Adverse events — posted to ClinicalTrials.gov

Time frame: During the first two cycles of therapy (roughly 12 weeks from initiation of therapy), or during a total of 24 weeks. Each patient will be assessed regularly for the development of any toxicity, 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).. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

First Intervention = Pregabalin

Serious: 0/5 (0%)

Deaths: 0/5

Second Intervention = Placebo

Serious: 0/4 (0%)

Deaths: 0/4

First Intervention = Placebo

Serious: 0/3 (0%)

Deaths: 0/3

Second Intervention = Pregabalin

Serious: 0/3 (0%)

Deaths: 0/3

Other adverse events (12 terms — click to expand)

Reaction	System	First Intervention = Prega…	Second Intervention = Plac…	First Intervention = Placebo	Second Intervention = Preg…
Dizziness	Nervous system disorders	—	—	—	—
Fatigue	General disorders	—	—	—	—
Nausea	Gastrointestinal disorders	—	—	—	—
Stomach pain	Gastrointestinal disorders	—	—	—	—
Pelvic pain	Reproductive system and breast disorders	—	—	—	—
Constipation	Gastrointestinal disorders	—	—	—	—
Drowsiness/Somnolence	Nervous system disorders	—	—	—	—
Diarrhea	Gastrointestinal disorders	—	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—	—
Headache	Nervous system disorders	—	—	—	—
Pain	General disorders	—	—	—	—
Bone pain	Musculoskeletal and connective tissue disorders	—	—	—	—

Data from ClinicalTrials.gov NCT03407430 adverse events section.

Sponsor's own description

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.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Multimodal evaluation of mannose engineered poly lactic glycolic acid nanoparticles with granulocyte colony stimulating factor focused delivery to bone marrow for neutropenia.
   Karwasra R, Bano N, Ahmad S, Singh S, et al · · 2026 · PMID 41565723 · DOI 10.1038/s41598-025-29790-w