Peripheral NeuropathyNCT02549534
Early Detection of Taxane-Induced Neuropathy in Women With Breast Cancer
An observational study of Peripheral Neuropathy, run by Indiana University at 2 sites in United States.
Trial summary
Purpose: The purpose of the study is to test a new way of measuring nerve damage in women with breast cancer receiving chemotherapy drug paclitaxel (Taxol). Read more about this study
- Who is it for?
- Ages 18 to 85 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Peripheral Neuropathy
- What is being tested?
- Axon Reflexes, Axon Flares and Self-Reported Signs & Symptoms of CIPN
- Type of treatment
- Surgery or procedure
- How many people
- 29 participants
- Where
- 2 sitesUnited States
- Study dates
- Sep 2015to Jul 2016
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Study population: Adult women with breast cancer (WBC) and healthy female controls (HCs)
Who may be able to join
- Age 18-85
- Able to read, write, and understand English
- Diagnosed with histologically-confirmed, first-time, non-metastatic breast cancer (stage I-IIIB)
- No prior exposure to neurotoxic chemotherapy or radiation at the time of enrollment,
- Will be receiving weekly paclitaxel (Taxol® or generic paclitaxel, 80- 100mg/m2) or bi-weekly Taxol (i.e., dose-dense; 175 mg/m2) as a part of their cancer treatment regimen OR
- Will be receiving an anthracycline and cyclophosphamide (AC) followed by weekly paclitaxel (Taxol® or generic paclitaxel, 80-100mg/m2) or bi-weekly Taxol (i.e., dose-dense; 175 mg/m2) as a part of their cancer treatment regimen;
- Aged 18-85
- Can read, write, and understand English
Who cannot join
- A history of cardiovascular disease, hypertension, or peripheral arterial/vascular disease;
- Current use of (1) medications/supplements to control blood pressure (e.g. beta-blockers, nitrates, calcium channel blockers, Phosphodiesterase-5 (PGE5) inhibitors) or (2) the use of statins for cholesterol;
- Suspected or diagnosed diabetes (with the exception of gestational diabetes);
- Pre-existing neuropathy, neuropathic pain, or nerve injury;
- Pain or significant arthritis in the toes of either foot;
- Current skin disease or fungal infection of the feet;
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- Significant damage or deformity to the feet that would alter blood flow or make it impossible to measure/interpret findings;
- Diagnosed or suspected vasospastic disease such as Raynaud's syndrome;
- Current use of tobacco/tobacco-containing products;
- Diagnosis of restless leg syndrome or other movement disorders that would prevent accurate data from being able to be collected.
- In-Study Restrictions:
- No caffeine- or alcohol-containing products for 12 hours prior to their study visit;
- No food for at least one hour prior to blood flow monitoring;
- No non-steroidal anti-inflammatory drugs (NSAIDS) for 24 hours prior to study visits unless directed by a physician to do so.
- (Note: These restrictions are designed to improve the rigor and quality of the data, but non-compliance will not be grounds for study exclusion; adherence to these restrictions will be monitored during self-report).
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Indiana University Melvin and Bren Simon Cancer Center (IUSCC)
Indianapolis, Indiana, 46202
Syndney & Lois Eskenazi Health Center
Indianapolis, Indiana, 46202
About this study
Purpose: The purpose of the study is to test a new way of measuring nerve damage in women with breast cancer receiving chemotherapy drug paclitaxel (Taxol).
Read the detailed description
Purpose: The study has four aims;
- The primary aim of the study is to determine whether women who are receiving either weekly Taxol (80-100 mg/m2) or bi-weekly Taxol (i.e.,dose-dense; 175 mg/m2) show deficits in axon-reflex mediated vasodilation (AMV) over the course of six weeks of Taxol therapy similar to those that have been reported in patients with diabetic and genetically-inherited neuropathies.
- The second aim of the study is to determine whether women who are receiving either weekly or dose-dense Taxol develop changes in AMV before developing signs \& symptoms of chemotherapy-induced peripheral neuropathy (CIPN) in a way that supports using changes in AMV as an early detection method for small-fiber CIPN.
- A third (exploratory) aim of the study is to determine whether any changes in AMV detected during the study are significantly correlated with self-reported CIPN in a way that would support using changes in AMV as a confirmatory marker for CIPN.
- A final (exploratory) aim of the study is to describe the size of axon reflexes and axon flares in women receiving weekly Taxol before they start their pre-Taxol anthracycline \& cyclophosphamide (AC) therapy.
- Conditions
- Peripheral Neuropathy
- Being tested
- Axon Reflexes, Axon Flares, Self-Reported Signs & Symptoms of CIPN
- Keywords
- Taxane, Neuropathy, Chemotherapy-Induced Peripheral Neuropathy (CIPN), Breast Cancer, Local skin heating, Axon reflex, Axon flare, Total Neuropathy Score (TNS), Laser Doppler Flowmetry (LDF), Laser Speckle Contrast Imaging (LSCI), Full-field laser perfusion imaging (FLPI), Paclitaxel, Taxol
- Medical subject headings
- Peripheral Nervous System Diseases, Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Axon ReflexesProcedure or surgery
*Axon reflexes will be evoked in the palmar surface of the right great toe using local skin heating with a 0.33 cm2 heat probe using the following protocol:
- Baseline: Heating the skin of the toe for a minimum of 5 minutes at 33*C.
- Heat Ramp: Increasing the heat in the heat probe to 42*C at approx. 0.1*C/10 sec.
- Skin Heating: Heating the skin of the toe for 30 minutes 42*C.
- Heat Ramp: Increasing the heat in the heat probe to 44*C at 0.1*C/10 sec..
- Skin Heating: Heating the skin for an additional 5 minutes at 44*C.
The size of the axon reflex during this skin heating protocol will be imaged using Laser Doppler Flowmetry (LDF). In the case that participants develop CIPN on their left side only, the left toe will be substituted.
Axon FlaresProcedure or surgery
Also called LDIflare, Heat-Evoked Axon Flare
Axon flares will be generated on the palmar surface of the right great toe using the same local skin heating protocol described above, and imaged using a laser speckle contrast imager (LSCI) (also known as full-field laser perfusion imager, or FLPI).
Self-Reported Signs & Symptoms of CIPNProcedure or surgery
Self-reported signs \& symptoms of CIPN such as the presence and location of (1) tingling, (2) numbness, and (3) neuropathic pain, along with information about (4) deficits in vibration thresholds, and (5) loss of deep tendon reflexes will be assessed at each study visit using the 5-item, modified Total Neuropathy Score (mTNS).
| Study group | Role | What they receive |
|---|---|---|
| Women with Breast Cancer (WBC) | Defined as women who:
* Are 18 to 85 years old at the time of enrollment;
* Have histologically-confirmed, first-time, non-metastatic breast cancer (Stage I-IIIB);
* Have no history of neurotoxic chemotherapy or radiation treatment at the time of enrollment;
* Will be receiving weekly paclitaxel (Taxol® or generic paclitaxel), 80-100mg/m2, or bi-weekly (i.e., dose-dense) Taxol, 175 mg/m2, as a part of their treatment regimen OR
* Will be receiving an anthracycline and cyclophosphamide (AC) therapy followed by weekly or bi-weekly (i.e., dose-dense; 175 mg/m2) paclitaxel (Taxol® or generic paclitaxel, 80-100mg/m2);
* Are willing to participate in up to four study sessions. Receives: Procedure: Axon Reflexes; Procedure: Axon Flares; Procedure: Self-Reported Signs & Symptoms of CIPN | |
| Healthy Female Controls (HCs) | Defined as women who:
* Are 18 to 85 years old at the time of study enrollment;
* Can read, write, and understand English,
* Are willing to participate in three planned study sessions. Receives: Procedure: Axon Reflexes; Procedure: Axon Flares; Procedure: Self-Reported Signs & Symptoms of CIPN |
What is being measured
The primary outcome is the main question the study is designed to answer.
Differences in the mean size of axon reflexes between healthy women and women with breast cancer BEFORE starting Taxol.
- Hypothesis: (Cross-Sectional): There WILL NOT be a significant difference in the mean size of axon reflexes (expressed as a %CVCmax) in the great toe between healthy women and women with breast cancer before they start Taxol (i.e., Day 1).
- Definitions/Notes: The mean size of axon reflexes will be determined by averaging the peak laser doppler values (in tissue perfusion units (TPUs)) that occur during a stable 30-90 second period after increasing the probe temperature to 42*C. The maximum circulatory vascular conductance (%CVCmax) for each participant will be determined by dividing the raw TPU values by the participant's mean arterial blood pressure (MAP) during the axon reflex. The size of axon reflexes for each group will be then calculated by averaging the %CVCmax values corresponding to each individual's axon reflex for each group at that time point. Differences between groups in the size of axon reflexes at Day 1 will be compared using two-tailed t-tests, α=0.05.
Measured: Day 1 (before participant's 1st Taxol infusion).
Differences in the mean size of axon reflexes between healthy women and women with breast cancer DURING Taxol therapy.
- Hypothesis (Cross-Sectional): There WILL be a significant difference in the mean size of axon reflexes generated on the palmar surface of the right great toe between healthy controls and women with breast cancer during their initial six weeks of Taxol therapy (i.e., day 14 and 42, respectively).
- Notes: The mean size of axon reflexes during Taxol therapy will be determined by averaging the size of axon reflexes for participants in each group at day 14 and 42, respectively. Differences between groups in the size of axon reflexes at day 14 and 42 will be compared using two-tailed t-tests, α=0.05.
Measured: Day 14 (week two of Taxol therapy) and Day 42 (week six of Taxol therapy).
Differences in the mean size of axon reflexes OVER TIME for women with breast during the initial six weeks of Taxol therapy.
- Hypothesis (Longitudinal): There WILL be a significant difference in the mean size of axon reflexes generated on the palmar surface of the great toe of women with breast cancer from (a) day 1 to day 14, (b) day 14 to day 42, and from (c) day 1 to day 42.
- Note: Differences in mean size of axon reflexes over the course of Taxol therapy will be calculated using repeated-measures analysis of covariance (RM-ANCOVA).
Measured: Day 1 (before participant's 1st Taxol infusion), day 14 (week two of Taxol therapy) and day 42 (week six of Taxol therapy).
Differences in the mean size of axon reflexes between healthy female controls OVER TIME the six-week study period.
- Hypothesis (Longitudinal): There WILL NOT be a significant difference in the size of axon reflexes on the palmar surface of the great toe of healthy female controls from(a) day 1 to day 14, (b) day 14 to day 42, and from (c) day 1 to day 42.
- Note: Differences in mean size of axon reflexes over the course of Taxol therapy will be calculated using repeated-measures analysis of covariance (RM-ANCOVA).
Measured: Day 1 (before participant's 1st Taxol infusion), Day 14 (week two of Taxol therapy) and Day 42 (week six of Taxol therapy).
Secondary outcomes (4)
Differences in the mean size of heat-evoked axon flares between healthy women and women with breast cancer BEFORE starting Taxol therapy.
- Hypothesis (Cross-Sectional): There WILL NOT be a significant difference in the mean size of heat-evoked axon flares generated on the palmar surface of the great toe between healthy women and women with breast cancer before starting Taxol therapy (day 1).
- Note: A "heat-evoked axon flare" is defined as the area of increased cutaneous blood flow surrounding heat probe that is at least three standard deviations (3SD) above blood flow measured during prior to local skin heating. The size of each axon flare will be expressed in centimeters squared (cm2). The mean size of axon flares for each group will be calculated by averaging the size of axon flares for healthy women at baseline and the size of axon flares for women with breast cancer at day 1 (before starting Taxol). Differences in the mean size of axon flares between both groups at day 1 will be compared using two-tailed t-tests, α=0.05.
Measured: Day 1 (before participant's 1st Taxol infusion).
Differences in the mean size of heat-evoked axon flares between healthy women and women with breast cancer DURING six weeks of study visits.
- Hypothesis (Cross-Sectional): There WILL be a significant difference in the mean size of heat-evoked axon flares generated on the palmar surface of the great toe between healthy controls and women with breast cancer DURING Taxol therapy at day 14 and 42 (respectively).
- Note: Differences in the size of heat-evoked axon flares between healthy women and women with breast cancer at days 14 and 42 (respectively) will be compared using separate, two-tailed t-tests, α=0.05.
Measured: Day 14 (week two of Taxol therapy) and Day 42 (week six of Taxol therapy).
Differences in the mean size of heat-evoked axon flares between women with breast cancer DURING their initial six weeks of Taxol therapy.
- Hypothesis (Longitudinal): There WILL be a significant difference in the mean size of heat-evoked axon flares generated on the palmar surface of great toe of women with breast cancer receiving Taxol from (a) day 1 to day 14, (b) day 14 to day 42, and from (c) day 1 to day 42.
- Differences in the size of heat-evoked axon flares during Taxol therapy will be evaluated using repeated-measures analysis of variance (RM-ANOVA).
Measured: Day 1 (before participant's 1st Taxol infusion), Day 14 (week two of Taxol therapy) and Day 42 (week six of Taxol therapy).
Differences in the size of heat-evoked axon flares for healthy women during the six-week study period.
- Hypothesis (Longitudinal): There WILL NOT be a significant difference in the size of heat-evoked axon flares (in cm2) generated on the great toe of healthy women from (a) day 1 to day 14, (b) day 14 to day 42, and from (c) day 1 to day 42.
- Differences in the size of heat-evoked axon flares during Taxol therapy will be evaluated using RM-ANOVA.
Measured: Day 1 (before participant's 1st Taxol infusion), Day 14 (week two of Taxol therapy) and Day 42 (week six of Taxol therapy).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Sep 2015 (estimated)
- Study startSep 2015
- Primary completionJul 2016
- Study completionJul 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (116)Papers the sponsor has linked to this study.
- Other trials for Peripheral NeuropathyStudies of the same condition, open and under way.
- More trials run by Indiana UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- Indiana University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Nursing Research (NINR), Midwest Nursing Research Society (MNRS), Council for the Advancement of Nursing Science (CANS), Indiana Center for Vascular Biology & Medicine (ICVBM)
- Responsible party
- Principal investigator, Victoria L. Champion, Indiana University
- Investigators
- Victoria L. Champion, PhD,RN,FAAN, Principal investigator, Indiana University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02549534
- Sponsor's protocol ID
- 1502603664
- Other IDs
- F31NR01521201A1
- Status last verified
- Oct 2017
- First submitted
- 9 Sep 2015
- Last updated
- 27 Oct 2017
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Golan-Vered Y, Pud D. Chemotherapy-induced neuropathic pain and its relation to cluster symptoms in breast cancer patients treated with paclitaxel. Pain Pract. 2013 Jan;13(1):46-52. doi: 10.1111/j.1533-2500.2012.00554.x. Epub 2012 Apr 26.
PubMed 22533683Hershman DL, Weimer LH, Wang A, Kranwinkel G, Brafman L, Fuentes D, Awad D, Crew KD. Association between patient reported outcomes and quantitative sensory tests for measuring long-term neurotoxicity in breast cancer survivors treated with adjuvant paclitaxel chemotherapy. Breast Cancer Res Treat. 2011 Feb;125(3):767-74. doi: 10.1007/s10549-010-1278-0. Epub 2010 Dec 3.
PubMed 21128110Wolf SL, Barton DL, Qin R, Wos EJ, Sloan JA, Liu H, Aaronson NK, Satele DV, Mattar BI, Green NB, Loprinzi CL. The relationship between numbness, tingling, and shooting/burning pain in patients with chemotherapy-induced peripheral neuropathy (CIPN) as measured by the EORTC QLQ-CIPN20 instrument, N06CA. Support Care Cancer. 2012 Mar;20(3):625-32. doi: 10.1007/s00520-011-1141-9. Epub 2011 Apr 12.
PubMed 21479990Forsyth PA, Balmaceda C, Peterson K, Seidman AD, Brasher P, DeAngelis LM. Prospective study of paclitaxel-induced peripheral neuropathy with quantitative sensory testing. J Neurooncol. 1997 Oct;35(1):47-53. doi: 10.1023/a:1005805907311.
PubMed 9266440O'Shaughnessy J, Gradishar WJ, Bhar P, Iglesias J. Nab-paclitaxel for first-line treatment of patients with metastatic breast cancer and poor prognostic factors: a retrospective analysis. Breast Cancer Res Treat. 2013 Apr;138(3):829-37. doi: 10.1007/s10549-013-2447-8. Epub 2013 Apr 6.
PubMed 23563958Park SB, Goldstein D, Krishnan AV, Lin CS, Friedlander ML, Cassidy J, Koltzenburg M, Kiernan MC. Chemotherapy-induced peripheral neurotoxicity: a critical analysis. CA Cancer J Clin. 2013 Nov-Dec;63(6):419-37. doi: 10.3322/caac.21204.
PubMed 24590861Osmani K, Vignes S, Aissi M, Wade F, Milani P, Levy BI, Kubis N. Taxane-induced peripheral neuropathy has good long-term prognosis: a 1- to 13-year evaluation. J Neurol. 2012 Sep;259(9):1936-43. doi: 10.1007/s00415-012-6442-5. Epub 2012 Feb 17.
PubMed 22349867Pignata S, De Placido S, Biamonte R, Scambia G, Di Vagno G, Colucci G, Febbraro A, Marinaccio M, Lombardi AV, Manzione L, Carteni G, Nardi M, Danese S, Valerio MR, de Matteis A, Massidda B, Gasparini G, Di Maio M, Pisano C, Perrone F. Residual neurotoxicity in ovarian cancer patients in clinical remission after first-line chemotherapy with carboplatin and paclitaxel: the Multicenter Italian Trial in Ovarian cancer (MITO-4) retrospective study. BMC Cancer. 2006 Jan 7;6:5. doi: 10.1186/1471-2407-6-5.
PubMed 16398939Speck RM, Sammel MD, Farrar JT, Hennessy S, Mao JJ, Stineman MG, DeMichele A. Impact of chemotherapy-induced peripheral neuropathy on treatment delivery in nonmetastatic breast cancer. J Oncol Pract. 2013 Sep;9(5):e234-40. doi: 10.1200/JOP.2012.000863. Epub 2013 Apr 30.
PubMed 23943894Boddy AV, Plummer ER, Todd R, Sludden J, Griffin M, Robson L, Cassidy J, Bissett D, Bernareggi A, Verrill MW, Calvert AH. A phase I and pharmacokinetic study of paclitaxel poliglumex (XYOTAX), investigating both 3-weekly and 2-weekly schedules. Clin Cancer Res. 2005 Nov 1;11(21):7834-40. doi: 10.1158/1078-0432.CCR-05-0803.
PubMed 16278406Sarosy G, Kohn E, Stone DA, Rothenberg M, Jacob J, Adamo DO, Ognibene FP, Cunnion RE, Reed E. Phase I study of taxol and granulocyte colony-stimulating factor in patients with refractory ovarian cancer. J Clin Oncol. 1992 Jul;10(7):1165-70. doi: 10.1200/JCO.1992.10.7.1165.
PubMed 1376773Rowinsky EK, Chaudhry V, Forastiere AA, Sartorius SE, Ettinger DS, Grochow LB, Lubejko BG, Cornblath DR, Donehower RC. Phase I and pharmacologic study of paclitaxel and cisplatin with granulocyte colony-stimulating factor: neuromuscular toxicity is dose-limiting. J Clin Oncol. 1993 Oct;11(10):2010-20. doi: 10.1200/JCO.1993.11.10.2010.
PubMed 7692001Wiernik PH, Schwartz EL, Strauman JJ, Dutcher JP, Lipton RB, Paietta E. Phase I clinical and pharmacokinetic study of taxol. Cancer Res. 1987 May 1;47(9):2486-93.
PubMed 2882837Hile ES, Fitzgerald GK, Studenski SA. Persistent mobility disability after neurotoxic chemotherapy. Phys Ther. 2010 Nov;90(11):1649-57. doi: 10.2522/ptj.20090405. Epub 2010 Sep 2.
PubMed 20813818Jones SE, Erban J, Overmoyer B, Budd GT, Hutchins L, Lower E, Laufman L, Sundaram S, Urba WJ, Pritchard KI, Mennel R, Richards D, Olsen S, Meyers ML, Ravdin PM. Randomized phase III study of docetaxel compared with paclitaxel in metastatic breast cancer. J Clin Oncol. 2005 Aug 20;23(24):5542-51. doi: 10.1200/JCO.2005.02.027.
PubMed 16110015
Study at a glance
From the registry record, last updated by the sponsor on 27 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Early Detection of Taxane-Induced Neuropathy in Women With Breast Cancer
- ClinicalTrials.gov ID
- NCT02549534
- Acronym / sponsor ID
- 1502603664
- Conditions
- Peripheral Neuropathy
- Keywords
- Taxane, Neuropathy, Chemotherapy-Induced Peripheral Neuropathy (CIPN), Breast Cancer, Local skin heating, Axon reflex, Axon flare, Total Neuropathy Score (TNS)
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- Indiana UniversityUniversity, hospital or other
- Collaborators
- National Institute of Nursing Research (NINR), Midwest Nursing Research Society (MNRS), Council for the Advancement of Nursing Science (CANS), Indiana Center for Vascular Biology & Medicine (ICVBM)
- Study start
- Sep 2015
- Primary completion
- Jul 2016 (actual)
- Study completion
- Jul 2016 (actual)
- First posted
- 15 Sep 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Purpose: The purpose of the study is to test a new way of measuring nerve damage in women with breast cancer receiving chemotherapy drug paclitaxel (Taxol).
Detailed description
Purpose: The study has four aims;
- The primary aim of the study is to determine whether women who are receiving either weekly Taxol (80-100 mg/m2) or bi-weekly Taxol (i.e.,dose-dense; 175 mg/m2) show deficits in axon-reflex mediated vasodilation (AMV) over the course of six weeks of Taxol therapy similar to those that have been reported in patients with diabetic and genetically-inherited neuropathies.
- The second aim of the study is to determine whether women who are receiving either weekly or dose-dense Taxol develop changes in AMV before developing signs \& symptoms of chemotherapy-induced peripheral neuropathy (CIPN) in a way that supports using changes in AMV as an early detection method for small-fiber CIPN.
- A third (exploratory) aim of the study is to determine whether any changes in AMV detected during the study are significantly correlated with self-reported CIPN in a way that would support using changes in AMV as a confirmatory marker for CIPN.
- A final (exploratory) aim of the study is to describe the size of axon reflexes and axon flares in women receiving weekly Taxol before they start their pre-Taxol anthracycline \& cyclophosphamide (AC) therapy.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Women with Breast Cancer (WBC) | – | Procedure: Axon Reflexes, Procedure: Axon Flares, Procedure: Self-Reported Signs & Symptoms of CIPNDefined as women who: * Are 18 to 85 years old at the time of enrollment; * Have histologically-confirmed, first-time, non-metastatic breast cancer (Stage I-IIIB); * Have no history of neurotoxic chemotherapy or radiation treatment at the time of enrollment; * Will be receiving weekly paclitaxel (Taxol® or generic paclitaxel), 80-100mg/m2, or bi-weekly (i.e., dose-dense) Taxol, 175 mg/m2, as a part of their treatment regimen OR * Will be receiving an anthracycline and cyclophosphamide (AC) therapy followed by weekly or bi-weekly (i.e., dose-dense; 175 mg/m2) paclitaxel (Taxol® or generic paclitaxel, 80-100mg/m2); * Are willing to participate in up to four study sessions. |
| Healthy Female Controls (HCs) | – | Procedure: Axon Reflexes, Procedure: Axon Flares, Procedure: Self-Reported Signs & Symptoms of CIPNDefined as women who: * Are 18 to 85 years old at the time of study enrollment; * Can read, write, and understand English, * Are willing to participate in three planned study sessions. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Adult women with breast cancer (WBC) and healthy female controls (HCs)
Key inclusion criteria (8 listed)
- Age 18-85
- Able to read, write, and understand English
- Diagnosed with histologically-confirmed, first-time, non-metastatic breast cancer (stage I-IIIB)
- No prior exposure to neurotoxic chemotherapy or radiation at the time of enrollment,
- Will be receiving weekly paclitaxel (Taxol® or generic paclitaxel, 80- 100mg/m2) or bi-weekly Taxol (i.e., dose-dense; 175 mg/m2) as a part of their cancer treatment regimen OR
Key exclusion criteria (15 listed)
- A history of cardiovascular disease, hypertension, or peripheral arterial/vascular disease;
- Current use of (1) medications/supplements to control blood pressure (e.g. beta-blockers, nitrates, calcium channel blockers, Phosphodiesterase-5 (PGE5) inhibitors) or (2) the use of statins for cholesterol;
- Suspected or diagnosed diabetes (with the exception of gestational diabetes);
- Pre-existing neuropathy, neuropathic pain, or nerve injury;
- Pain or significant arthritis in the toes of either foot;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Axon Reflexes*Axon reflexes will be evoked in the palmar surface of the right great toe using local skin heating with a 0.33 cm2 heat probe using the following protocol: * Baseline: Heating the skin of the toe for a minimum of 5 minutes at 33*C. * Heat Ramp: Increasing the heat in the heat probe to 42*C at approx. 0.1*C/10 sec. * Skin Heating: Heating the skin of the toe for 30 minutes 42*C. * Heat Ramp: Increasing the heat in the heat probe to 44*C at 0.1*C/10 sec.. * Skin Heating: Heating the skin for an additional 5 minutes at 44*C. The size of the axon reflex during this skin heating protocol will be imaged using Laser Doppler Flowmetry (LDF). In the case that participants develop CIPN on their left side only, the left toe will be substituted. | Procedure or surgery | Healthy Female Controls (HCs), Women with Breast Cancer (WBC) |
| Axon FlaresAlso: LDIflare, Heat-Evoked Axon FlareAxon flares will be generated on the palmar surface of the right great toe using the same local skin heating protocol described above, and imaged using a laser speckle contrast imager (LSCI) (also known as full-field laser perfusion imager, or FLPI). | Procedure or surgery | Healthy Female Controls (HCs), Women with Breast Cancer (WBC) |
| Self-Reported Signs & Symptoms of CIPNSelf-reported signs \& symptoms of CIPN such as the presence and location of (1) tingling, (2) numbness, and (3) neuropathic pain, along with information about (4) deficits in vibration thresholds, and (5) loss of deep tendon reflexes will be assessed at each study visit using the 5-item, modified Total Neuropathy Score (mTNS). | Procedure or surgery | Healthy Female Controls (HCs), Women with Breast Cancer (WBC) |
Primary outcome
Differences in the mean size of axon reflexes between healthy women and women with breast cancer BEFORE starting Taxol.
Time frame: Day 1 (before participant's 1st Taxol infusion).
* Hypothesis: (Cross-Sectional): There WILL NOT be a significant difference in the mean size of axon reflexes (expressed as a %CVCmax) in the great toe between healthy women and women with breast cancer before they start Taxol (i.e., Day 1). * Definitions/Notes: The mean size of axon reflexes will be determined by averaging the peak laser doppler values (in tissue perfusion units (TPUs)) that occur during a stable 30-90 second period after increasing the probe temperature to 42*C. The maximum circulatory vascular conductance (%CVCmax) for each participant will be determined by dividing the raw TPU values by the participant's mean arterial blood pressure (MAP) during the axon reflex. The size of axon reflexes for each group will be then calculated by averaging the %CVCmax values corresponding to each individual's axon reflex for each group at that time point. Differences between groups in the size of axon reflexes at Day 1 will be compared using two-tailed t-tests, α=0.05.
Differences in the mean size of axon reflexes between healthy women and women with breast cancer DURING Taxol therapy.
Time frame: Day 14 (week two of Taxol therapy) and Day 42 (week six of Taxol therapy).
* Hypothesis (Cross-Sectional): There WILL be a significant difference in the mean size of axon reflexes generated on the palmar surface of the right great toe between healthy controls and women with breast cancer during their initial six weeks of Taxol therapy (i.e., day 14 and 42, respectively). * Notes: The mean size of axon reflexes during Taxol therapy will be determined by averaging the size of axon reflexes for participants in each group at day 14 and 42, respectively. Differences between groups in the size of axon reflexes at day 14 and 42 will be compared using two-tailed t-tests, α=0.05.
Differences in the mean size of axon reflexes OVER TIME for women with breast during the initial six weeks of Taxol therapy.
Time frame: Day 1 (before participant's 1st Taxol infusion), day 14 (week two of Taxol therapy) and day 42 (week six of Taxol therapy).
* Hypothesis (Longitudinal): There WILL be a significant difference in the mean size of axon reflexes generated on the palmar surface of the great toe of women with breast cancer from (a) day 1 to day 14, (b) day 14 to day 42, and from (c) day 1 to day 42. * Note: Differences in mean size of axon reflexes over the course of Taxol therapy will be calculated using repeated-measures analysis of covariance (RM-ANCOVA).
Differences in the mean size of axon reflexes between healthy female controls OVER TIME the six-week study period.
Time frame: Day 1 (before participant's 1st Taxol infusion), Day 14 (week two of Taxol therapy) and Day 42 (week six of Taxol therapy).
* Hypothesis (Longitudinal): There WILL NOT be a significant difference in the size of axon reflexes on the palmar surface of the great toe of healthy female controls from(a) day 1 to day 14, (b) day 14 to day 42, and from (c) day 1 to day 42. * Note: Differences in mean size of axon reflexes over the course of Taxol therapy will be calculated using repeated-measures analysis of covariance (RM-ANCOVA).
4 secondary outcomes
Differences in the mean size of heat-evoked axon flares between healthy women and women with breast cancer BEFORE starting Taxol therapy.
Time frame: Day 1 (before participant's 1st Taxol infusion).
Differences in the mean size of heat-evoked axon flares between healthy women and women with breast cancer DURING six weeks of study visits.
Time frame: Day 14 (week two of Taxol therapy) and Day 42 (week six of Taxol therapy).
Differences in the mean size of heat-evoked axon flares between women with breast cancer DURING their initial six weeks of Taxol therapy.
Time frame: Day 1 (before participant's 1st Taxol infusion), Day 14 (week two of Taxol therapy) and Day 42 (week six of Taxol therapy).
Differences in the size of heat-evoked axon flares for healthy women during the six-week study period.
Time frame: Day 1 (before participant's 1st Taxol infusion), Day 14 (week two of Taxol therapy) and Day 42 (week six of Taxol therapy).
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Oct 2017.
- Background: PubMed 22533683Golan-Vered Y, Pud D. Chemotherapy-induced neuropathic pain and its relation to cluster symptoms in breast cancer patients treated with paclitaxel. Pain Pract. 2013 Jan;13(1):46-52. doi: 10.1111/j.1533-2500.2012.00554.x. Epub 2012 Apr 26.
- Background: PubMed 21128110Hershman DL, Weimer LH, Wang A, Kranwinkel G, Brafman L, Fuentes D, Awad D, Crew KD. Association between patient reported outcomes and quantitative sensory tests for measuring long-term neurotoxicity in breast cancer survivors treated with adjuvant paclitaxel chemotherapy. Breast Cancer Res Treat. 2011 Feb;125(3):767-74. doi: 10.1007/s10549-010-1278-0. Epub 2010 Dec 3.
- Background: PubMed 21479990Wolf SL, Barton DL, Qin R, Wos EJ, Sloan JA, Liu H, Aaronson NK, Satele DV, Mattar BI, Green NB, Loprinzi CL. The relationship between numbness, tingling, and shooting/burning pain in patients with chemotherapy-induced peripheral neuropathy (CIPN) as measured by the EORTC QLQ-CIPN20 instrument, N06CA. Support Care Cancer. 2012 Mar;20(3):625-32. doi: 10.1007/s00520-011-1141-9. Epub 2011 Apr 12.
- Background: PubMed 9266440Forsyth PA, Balmaceda C, Peterson K, Seidman AD, Brasher P, DeAngelis LM. Prospective study of paclitaxel-induced peripheral neuropathy with quantitative sensory testing. J Neurooncol. 1997 Oct;35(1):47-53. doi: 10.1023/a:1005805907311.
- Background: PubMed 23563958O'Shaughnessy J, Gradishar WJ, Bhar P, Iglesias J. Nab-paclitaxel for first-line treatment of patients with metastatic breast cancer and poor prognostic factors: a retrospective analysis. Breast Cancer Res Treat. 2013 Apr;138(3):829-37. doi: 10.1007/s10549-013-2447-8. Epub 2013 Apr 6.
- Background: PubMed 24590861Park SB, Goldstein D, Krishnan AV, Lin CS, Friedlander ML, Cassidy J, Koltzenburg M, Kiernan MC. Chemotherapy-induced peripheral neurotoxicity: a critical analysis. CA Cancer J Clin. 2013 Nov-Dec;63(6):419-37. doi: 10.3322/caac.21204.
- Background: PubMed 22349867Osmani K, Vignes S, Aissi M, Wade F, Milani P, Levy BI, Kubis N. Taxane-induced peripheral neuropathy has good long-term prognosis: a 1- to 13-year evaluation. J Neurol. 2012 Sep;259(9):1936-43. doi: 10.1007/s00415-012-6442-5. Epub 2012 Feb 17.
- Background: PubMed 16398939Pignata S, De Placido S, Biamonte R, Scambia G, Di Vagno G, Colucci G, Febbraro A, Marinaccio M, Lombardi AV, Manzione L, Carteni G, Nardi M, Danese S, Valerio MR, de Matteis A, Massidda B, Gasparini G, Di Maio M, Pisano C, Perrone F. Residual neurotoxicity in ovarian cancer patients in clinical remission after first-line chemotherapy with carboplatin and paclitaxel: the Multicenter Italian Trial in Ovarian cancer (MITO-4) retrospective study. BMC Cancer. 2006 Jan 7;6:5. doi: 10.1186/1471-2407-6-5.
- Background: PubMed 23943894Speck RM, Sammel MD, Farrar JT, Hennessy S, Mao JJ, Stineman MG, DeMichele A. Impact of chemotherapy-induced peripheral neuropathy on treatment delivery in nonmetastatic breast cancer. J Oncol Pract. 2013 Sep;9(5):e234-40. doi: 10.1200/JOP.2012.000863. Epub 2013 Apr 30.
- Background: PubMed 16278406Boddy AV, Plummer ER, Todd R, Sludden J, Griffin M, Robson L, Cassidy J, Bissett D, Bernareggi A, Verrill MW, Calvert AH. A phase I and pharmacokinetic study of paclitaxel poliglumex (XYOTAX), investigating both 3-weekly and 2-weekly schedules. Clin Cancer Res. 2005 Nov 1;11(21):7834-40. doi: 10.1158/1078-0432.CCR-05-0803.
- Background: PubMed 1376773Sarosy G, Kohn E, Stone DA, Rothenberg M, Jacob J, Adamo DO, Ognibene FP, Cunnion RE, Reed E. Phase I study of taxol and granulocyte colony-stimulating factor in patients with refractory ovarian cancer. J Clin Oncol. 1992 Jul;10(7):1165-70. doi: 10.1200/JCO.1992.10.7.1165.
- Background: PubMed 7692001Rowinsky EK, Chaudhry V, Forastiere AA, Sartorius SE, Ettinger DS, Grochow LB, Lubejko BG, Cornblath DR, Donehower RC. Phase I and pharmacologic study of paclitaxel and cisplatin with granulocyte colony-stimulating factor: neuromuscular toxicity is dose-limiting. J Clin Oncol. 1993 Oct;11(10):2010-20. doi: 10.1200/JCO.1993.11.10.2010.
- Gracias N. Paclitaxel alters the function of the small diameter sensory neurons. \[Dissertation\]. United States--Indiana, Indiana University; 2011.Link provided by the sponsor.
- Bruning RS. The mechanisms and functional implications of altered microvascular vasoreactivity in healthy and essential hypertensive men and women \[Ph.D.\]. Ann Arbor: The Pennsylvania State University; 2013.Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Victoria L. Champion, PhD,RN,FAAN principal investigator
Indiana University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Peripheral Neuropathy, run by Indiana University at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Differences in the mean size of axon reflexes between healthy women and women with breast cancer BEFORE starting Taxol. (time frame: Day 1 (before participant's 1st Taxol infusion).). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02549534, which also lists 116 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Oct 2017.