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

Phase 2

Completed

Conditions: Pain

Interventions: Drug: auranofin
Other: placebo
Other: questionnaire administration

Registration Number: NCT02063698

Lead Sponsor: Mayo Clinic

Brief Summary: 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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 30

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm I (auranofin)	questionnaire administration	Patients receive auranofin PO on day 2.
Arm I (auranofin)	auranofin	Patients receive auranofin PO on day 2.
Arm II (placebo)	placebo	Patients receive placebo PO on day 2.
Arm II (placebo)	questionnaire administration	Patients receive placebo PO on day 2.

Primary Outcome Measures

Name	Time	Method
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)	Up to 28 days	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.
Area Under the Curve (AUC) Summary of Worst Pain in the Last 24 Hours From Days 2 to 8	Up to 8 days	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.

Secondary Outcome Measures

Name	Time	Method
Normalized AUC for BPI Average Pain From the Modified BPI in the Last 24 Hours From Days 2 to 8	Up to 28 days	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.
Worst Toxicity Assessed Using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4	Up to 28 days	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.
Location of New Pain Patient Had in the Last 24 Hours on Day 5 PIAPS Upper Arm Pain	Up to 5 days	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.
Cramp Pain as Measured by the Paclitaxel-Induced Acute Pain Syndrome (PIAPS) Symptom Summary on Day 5	Up to 5 days	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.
Gnawing Pain as Measure by the Paclitaxel-Induced Acute Pain Syndrome (PIAPS) Symptom Summary on Day 8	Up to 8 days	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.
Location of New Pain Patient Had in the Last 24 Hours on Day 6 PIAPS Lower Arm Pain.	Up to 6 days	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.
Location of New Pain Patient Had in the Last 24 Hours on Day 5 PIAPS Lower Arm Pain.	Up to 5 days	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.