Auranofin in Decreasing Pain in Patients With Paclitaxel-Induced Pain Syndrome

A Pilot Randomized, Placebo-Controlled Study to Test Auranofin (Ridaura®) to Control the Paclitaxel-Induced Pain Syndrome (PIAPS)

This randomized pilot clinical trial studies whether auranofin will relieve pain following paclitaxel in patients who have previously experienced paclitaxel-induced pain. Auranofin is a drug given by mouth to treat other diseases such as rheumatoid arthritis, and is being studied to see if it will decrease pain following paclitaxel.

Study Overview

• Status: Completed
• Conditions: Pain
• Intervention / Treatment: Other: questionnaire administration; Other: placebo; Drug: auranofin

Detailed Description

PRIMARY OBJECTIVES:

I. Determine whether one dose of auranofin given the day following administration of paclitaxel decreases pain as assessed by daily completion of the Modified Brief Pain Inventory scale for seven days.

SECONDARY OBJECTIVES:

I. Assess whether auranofin is well tolerated in this setting.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive auranofin orally (PO) on day 2.

ARM II: Patients receive placebo PO on day 2.

After completion of study treatment, patients are followed up at 21-28 days.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Absolute neutrophil count (ANC) >= 1500/mm^3
• Platelet count (PLT) >= 100,000/mm^3
• Creatinine =< 2 x upper limit of normal (ULN)
• Either serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) or serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) =< 1.5 x ULN
• Total/direct bilirubin =< 1.5 x ULN
• Alkaline phosphatase =< 1.5 x ULN
• Hemoglobin >= 9 mg/dL
• Negative urine or serum pregnancy test performed =< 7 days prior to registration, for women of childbearing potential only
• Previously experienced paclitaxel induced pain during a current or past paclitaxel treatment that the treating healthcare provider thinks is consistent with the paclitaxel-induced acute pain syndrome; note: formal documentation of prior pain is not required
• Scheduled to receive paclitaxel at a dose >= 70 mg/m^2 =< 14 days from randomization
• Ability to complete the questionnaires or to do so with assistance

Exclusion Criteria:

• Pregnant women
• Nursing women
• Any woman of childbearing potential or male partner of a woman of childbearing potential unwilling to employ acceptable contraception throughout the study and for at least 30 days after the last dose of the study drug
• History of gold-induced disorders, including but not limited to, necrotizing enterocolitis, pulmonary fibrosis, exfoliative dermatitis, bone marrow aplasias or other severe hematologic disorders; history of severe allergic or anaphylactic reactions or hypersensitivity to auranofin or other gold compounds
• Currently receiving Dilantin (phenytoin) or auranofin or another gold-containing compound
• Anticipated use of filgrastim (G-CSF) or sargramostim (GM-CSF) within 30 days after receiving auranofin
• Currently receiving immune-modulating therapies

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (auranofin); Patients receive auranofin PO on day 2.	Other: questionnaire administration; Ancillary studies; Drug: auranofin; Given PO; Other Names: Ridaura
Placebo Comparator: Arm II (placebo); Patients receive placebo PO on day 2.	Other: questionnaire administration; Ancillary studies; Other: placebo; Given PO; Other Names: PLCB

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Count/Percentage of Patients Who Report Having Experienced the Paclitaxel-induced Pain Syndrome (PIAPS) for One Week After Paclitaxel After Enrollment to the Current Trial, Assessed by the Modified Brief Pain Inventory Scale (BPI)	The primary endpoint is the per arm count/percentage of patients who report having experienced the PIAPS for one week after paclitaxel after enrollment to the current trial. Pain was assessed on the question 'Please rate your pain by circling the one number that best describes your pain at its worst in the last 24 hours'. The count of participants who report having experienced the PIAPS for one week after paclitaxel after enrollment to the current trial circling 'less than 4' and 'greater than or equal to 4' for each day between day 2 to day 8 are reported below. Modified Brief Pain Inventory (BPI) ranges from 0 to 10, with higher scores corresponding to more /worse pain. Fisher's Exact Test will be used to compare the frequency of patients who experienced PIAPS between the two arms.	Up to 28 days
Area Under the Curve (AUC) Summary of Worst Pain in the Last 24 Hours From Days 2 to 8	Area under the curve (AUC) Summary of Worst Pain in the last 24 hours from days 2 to 8. On a scale of 0-100, with 100=Best QOL. Pain was assessed on the question 'Please rate your pain by circling the one number that best describes your pain at its worst in the last 24 hours.' Modified Brief Pain Inventory (BPI) ranges from 0 to 10, with higher scores corresponding to more pain. The AUC for this question was then calculated and ranged from 0-100, with higher scores corresponding to less/improved pain. The Equal Variance T-test will be used to compare the average AUC for worst pain between the two arms.	Up to 8 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Normalized AUC for BPI Average Pain From the Modified BPI in the Last 24 Hours From Days 2 to 8	Normalized AUC for BPI Average pain from the modified BPI in the last 24 hours from days 2 to 8. On a scale of 0-100 with 100:Best QOL. Pain was assessed on the question 'Please rate your pain by circling the one number that best describes your pain on the average.' Modified Brief Pain Inventory (BPI) ranges from 0 to 10, with higher scores corresponding to more pain. The AUC for this question was then calculated and ranged from 0-100, with higher scores corresponding to less/improved pain. The Equal Variance T-test will be used to compare the average AUC for worst pain between the two arms.	Up to 28 days
Worst Toxicity Assessed Using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4	The maximum grade for each type of toxicity will be recorded for each patient. The count of participants with worst adverse events considered at least possibly related to treatment by maximum grade are reported below.	Up to 28 days
Cramp Pain as Measured by the Paclitaxel-Induced Acute Pain Syndrome (PIAPS) Symptom Summary on Day 5	Cramp Pain as measured by the Paclitaxel-Induced Acute Pain Syndrome (PIAPS) Symptom Summary on Day 5. The PIAPS question 'Please place a check mark (√) by all appropriate words that could be used to describe any pain you have had in the last 24 hours'. The number of participants who completed this question on day 5 were analyzed (those who checked 'cramping' are summarized by the 'Yes' row below and those who did not check 'cramping' are summarized by the 'No' row below. Those who did not complete the symptom summary are summarized by the 'Missing' row.) The chi-square test was used.	Up to 5 days
Gnawing Pain as Measure by the Paclitaxel-Induced Acute Pain Syndrome (PIAPS) Symptom Summary on Day 8	Gnawing Pain as measured by the Paclitaxel-Induced Acute Pain Syndrome (PIAPS) Symptom Summary on Day 8. The PIAPS question 'Please place a check mark (√) by all appropriate words that could be used to describe any pain you have had in the last 24 hours'. The number of participants who completed this question on day 8 were analyzed (those who checked 'gnawing' are summarized by the 'Yes' row below and those who did not check 'gnawing' are summarized by the 'No' row below. Those who did not complete the symptom summary are summarized by the 'Missing' row.) The chi-square test was used.	Up to 8 days
Location of New Pain Patient Had in the Last 24 Hours on Day 5 PIAPS Upper Arm Pain	Location of New Pain Patient had in the last 24 hours on day 5 PIAPS Upper arm pain. PIAPS question: "Please indicate where any new pains are/were located by placing a check mark (√) next to the location. Please mark all that apply:" The number of participants who completed this question on day 5 were analyzed (those who checked 'arm, above the elbow' are summarized by the 'Yes' row below and those who did not check 'arm, above the elbow' are summarized by the 'No' row below. Those who did not complete the symptom summary are summarized by the 'Missing' row.) The chi-square test was used.	Up to 5 days
Location of New Pain Patient Had in the Last 24 Hours on Day 5 PIAPS Lower Arm Pain.	Location of New Pain Patient had in the last 24 hours on day 5 PIAPS Lower arm pain. PIAPS question: "Please indicate where any new pains are/were located by placing a check mark (√) next to the location. Please mark all that apply:" The number of participants who completed this question on day 5 were analyzed (those who checked 'arm, between the elbows and wrists' are summarized by the 'Yes' row below and those who did not check 'arm, between the elbows and wrists' are summarized by the 'No' row below. Those who did not complete the symptom summary are summarized by the 'Missing' row.) The chi-square test was used.	Up to 5 days
Location of New Pain Patient Had in the Last 24 Hours on Day 6 PIAPS Lower Arm Pain.	Location of New Pain Patient had in the last 24 hours on day 6 PIAPS Lower arm pain. PIAPS question: "Please indicate where any new pains are/were located by placing a check mark (√) next to the location. Please mark all that apply:" The number of participants who completed this question on day 5 were analyzed (those who checked 'arm, between the elbows and wrists' are summarized by the 'Yes' row below and those who did not check 'arm, between the elbows and wrists' are summarized by the 'No' row below. Those who did not complete the symptom summary are summarized by the 'Missing' row.) The chi-square test was used.	Up to 6 days

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start (Actual): February 19, 2014
• Primary Completion (Actual): November 11, 2015
• Study Completion (Actual): November 11, 2016

Study Registration Dates

• First Submitted: February 12, 2014
• First Submitted That Met QC Criteria: February 12, 2014
• First Posted (Estimate): February 14, 2014

Study Record Updates

• Last Update Posted (Actual): April 23, 2019
• Last Update Submitted That Met QC Criteria: April 2, 2019
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Antirheumatic Agents; Auranofin
• Other Study ID Numbers: MC1364 (Other Identifier: Mayo Clinic); P30CA015083 (U.S. NIH Grant/Contract); NCI-2014-00165 (Registry Identifier: CTRP (Clinical Trial Reporting Program))