Topical Cryotherapy in Reducing Pain in Patients With Chemotherapy Induced Peripheral Neuropathy or Paclitaxel Induced Acute Pain Syndrome

• Sponsor: Academic and Community Cancer Research United (Other)
• Overall Status: Completed
• CT.gov ID: NCT02640053
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 46
• Locations: 8
• Arms: 2
• Actual Duration (Months): 33.4
• Patients Per Site: 5.8
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This randomized pilot clinical trial studies topical cryotherapy (cooling hands and feet with ice bags) in reducing pain in patients with chemotherapy induced peripheral neuropathy or paclitaxel induced acute pain syndrome. Peripheral neuropathy is a nerve problem that causes pain, numbness, tingling, swelling, or muscle weakness in different parts of the body. Paclitaxel produces a disabling syndrome of acute aches and pains. Topical cryotherapy is being studied to see if it can help relieve pain from peripheral neuropathy or acute pain syndrome caused by chemotherapy.

Condition or Disease	Intervention/Treatment	Phase
Breast Carcinoma	Procedure: Cryotherapy; Drug: Paclitaxel; Other: Quality-of-Life Assessment; Other: Questionnaire Administration	N/A

Detailed Description

PRIMARY OBJECTIVES:

1. To estimate whether topical cryotherapy can alleviate paclitaxel-induced peripheral neuropathy.

2. To estimate whether topical cryotherapy can alleviate paclitaxel-induced acute pain syndrome (P-APS).

3. To examine the possible relative toxicities related to topical cryotherapy in this study situation.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients apply bags filled with crushed ice to hands and feet for 15 minutes before, for 60 minutes during administration, and for 15 minutes after finishing administration of paclitaxel.

ARM II: Patients receive paclitaxel intravenously (IV) over 60 minutes on weeks 1-12.

In both arms, courses repeat once a week for 12 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 30 days for 6 months.

Study Design

• Study Type: Interventional
• Actual Enrollment: 46 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Pilot Clinical Trial Evaluating the Utility of Topical Cryotherapy to Decrease Chemotherapy-Induced Peripheral Neuropathy (CIPN) and Paclitaxel-Induced Acute Pain Syndrome (P-APS): A Randomized Controlled Trial
• Actual Study Start Date: Dec 23, 2015
• Actual Primary Completion Date: Sep 5, 2017
• Actual Study Completion Date: Oct 5, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I (topical cryotherapy, paclitaxel) Patients apply bags filled with crushed ice to hands and feet for 15 minutes before, for 60 minutes during administration, and for 15 minutes after finishing administration of paclitaxel. Courses repeat once a week for 12 weeks in the absence of disease progression or unacceptable toxicity.	Procedure: Cryotherapy; Applied topically; Drug: Paclitaxel; Given IV; Other Names: Anzatax Asotax Bristaxol Praxel Taxol Taxol Konzentrat ; Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment ; Other: Questionnaire Administration; Ancillary studies
Active Comparator: Arm II (paclitaxel) Patients receive paclitaxel IV over 60 minutes on weeks 1-12. Courses repeat once a week for 12 weeks in the absence of disease progression or unacceptable toxicity.	Drug: Paclitaxel; Given IV; Other Names: Anzatax Asotax Bristaxol Praxel Taxol Taxol Konzentrat ; Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment ; Other: Questionnaire Administration; Ancillary studies

Outcome Measures

Primary Outcome Measures

1. Area Under the Curve (AUC) EORTC CIPN20 Sensory Neuropathy Subscale Adjusting for Baseline [Up to 12 weeks]

   Average Area Under the Curve per assessment (aAUCpa) of EORTC Chemotherapy-Induced Peripheral Neuropathy Module (EORTC QLQ-CIPN20) Sensory Neuropathy Subscale adjusting for baseline. The EORTC CIPN20 scoring algorithm was used for the sensory (items 31-36, 39, 40 and 48) subscale scores on a 0-100 scale, with higher scores represent fewer symptoms (better QOL). The aAUCpa for the subscale is calculated as the average of each AUC between each sequential assessment from pre-treatment-initiation to the week-12 assessment then subtract the corresponding baseline Sensory Neuropathy subscale score, with positive scores represent symptoms has improved from baseline and negative scores represent symptoms has worsen from baseline.

2. Area Under the Curve (AUC) EORTC CIPN20 Tingling Fingers or Hands Item Adjusting for Baseline [Up to 12 weeks]

   Average Area Under the Curve per assessment (aAUCpa) of EORTC Chemotherapy-Induced Peripheral Neuropathy Module (EORTC QLQ-CIPN20) Tingling Fingers or Hands over 12 weeks adjusting for baseline (item 1; "During the past week, did you have tingling fingers or hands?"; 1=Not at all, 2=A little, 3=Quite a bit; and 4=Very much). The reported score was transform into 0-100 scale, with higher scores represent fewer symptoms (better QOL). The aAUCpa for the individual item is calculated as the average of each AUC between each sequential assessment from pre-treatment-initiation to the week-12 assessment then subtract the corresponding baseline score, with positive scores represent symptoms has improved from baseline and negative scores represent symptoms has worsen from baseline.

3. Area Under the Curve (AUC) EORTC CIPN20 Tingling Toes or Feet Item Adjusting for Baseline [Up to 12 weeks]

   Average Area Under the Curve per assessment (aAUCpa) of EORTC Chemotherapy-Induced Peripheral Neuropathy Module (EORTC QLQ-CIPN20) Tingling Toes or Feet over 12 weeks adjusting for baseline (item 1; "During the past week, did you have tingling toes or feet?"; 1=Not at all, 2=A little, 3=Quite a bit; and 4=Very much). The reported score was transform into 0-100 scale, with higher scores represent fewer symptoms (better QOL). The aAUCpa for the individual item is calculated as the average of each AUC between each sequential assessment from pre-treatment-initiation to the week-12 assessment then subtract the corresponding baseline score, with positive scores represent symptoms has improved from baseline and negative scores represent symptoms has worsen from baseline.

4. Area Under the Curve (AUC) EORTC CIPN20 Numbness Fingers or Hands Item Adjusting for Baseline [Up to 12 weeks]

   Average Area Under the Curve per assessment (aAUCpa) of EORTC Chemotherapy-Induced Peripheral Neuropathy Module (EORTC QLQ-CIPN20) Numbness Fingers or Hands over 12 weeks adjusting for baseline (item 1; "During the past week, did you have numbness in your fingers or hands?"; 1=Not at all, 2=A little, 3=Quite a bit; and 4=Very much). The reported score was transform into 0-100 scale, with higher scores represent fewer symptoms (better QOL). The aAUCpa for the individual item is calculated as the average of each AUC between each sequential assessment from pre-treatment-initiation to the week-12 assessment then subtract the corresponding baseline score, with positive scores represent symptoms has improved from baseline and negative scores represent symptoms has worsen from baseline.

5. Area Under the Curve (AUC) EORTC CIPN20 Numbness Toes or Feet Item Adjusting for Baseline [Up to 12 weeks]

   Average Area Under the Curve per assessment (aAUCpa) of EORTC Chemotherapy-Induced Peripheral Neuropathy Module (EORTC QLQ-CIPN20) Numbness Toes or Feet over 12 weeks adjusting for baseline (item 1; "During the past week, did you have numbness in your toes or feet?"; 1=Not at all, 2=A little, 3=Quite a bit; and 4=Very much). The reported score was transform into 0-100 scale, with higher scores represent fewer symptoms (better QOL). The aAUCpa for the individual item is calculated as the average of each AUC between each sequential assessment from pre-treatment-initiation to the week-12 assessment then subtract the corresponding baseline score, with positive scores represent symptoms has improved from baseline and negative scores represent symptoms has worsen from baseline.

6. Area Under the Curve (AUC) EORTC CIPN20 Shooting/Burning Pain in Fingers or Hands Item Adjusting for Baseline [Up to 12 weeks]

   Average Area Under the Curve per assessment (aAUCpa) of EORTC Chemotherapy-Induced Peripheral Neuropathy Module (EORTC QLQ-CIPN20) Shooting/Burning Pain in Fingers or Hands over 12 weeks adjusting for baseline (item 1; "During the past week, did you have shooting or burning pain in your fingers or hands?"; 1=Not at all, 2=A little, 3=Quite a bit; and 4=Very much). The reported score was transform into 0-100 scale, with higher scores represent fewer symptoms (better QOL). The aAUCpa for the individual item is calculated as the average of each AUC between each sequential assessment from pre-treatment-initiation to the week-12 assessment then subtract the corresponding baseline score, with positive scores represent symptoms has improved from baseline and negative scores represent symptoms has worsen from baseline.

7. Area Under the Curve (AUC) EORTC CIPN20 Shooting/Burning Pain in Toes or Feet Item Adjusting for Baseline [Up to 12 weeks]

   Average Area Under the Curve per assessment (aAUCpa) of EORTC Chemotherapy-Induced Peripheral Neuropathy Module (EORTC QLQ-CIPN20) Shooting/Burning Pain in Toes or Feet over 12 weeks adjusting for baseline (item 1; "During the past week, did you have shooting or burning pain in your Toes or Feet?"; 1=Not at all, 2=A little, 3=Quite a bit; and 4=Very much). The reported score was transform into 0-100 scale, with higher scores represent fewer symptoms (better QOL). The aAUCpa for the individual item is calculated as the average of each AUC between each sequential assessment from pre-treatment-initiation to the week-12 assessment then subtract the corresponding baseline score, with positive scores represent symptoms has improved from baseline and negative scores represent symptoms has worsen from baseline.

Secondary Outcome Measures

1. Area Under the Curve (AUC) Per Assessment (aAUCpa) of Worst Pain (Item 1 on the Daily Post-Paclitaxel Questionnaire) [1 week]

   Average Area Under the Curve (AUC) per assessment (aAUCpa) of worst pain (item 1 on the Daily Post-Paclitaxel Questionnaire; "Please rate any aches/pain that are new since your last dose of paclitaxel, and that you think might be related to your chemotherapy treatment, by circling ONE number that best describes your aches/pain at its WORST in the last 24 hours.") over 1 week. Scores are reported on a 0-100 scale, where 100=better outcome quality of life (QOL). The aAUCpa is the average of each AUC between each sequential assessment from day 2 through 7 following paclitaxel.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Ability to complete questionnaires by themselves or with assistance

• Planned paclitaxel at a dose of 80 mg/m^2 intravenously (I.V.) given, in the adjuvant breast cancer (postoperative or neo-adjuvant) setting, every week for a planned course of 12 weeks without any other concurrent cytotoxic chemotherapy (NOTE: trastuzumab and/or other antibody and/or small molecule treatment is allowed, except for poly adenosine diphosphate ribose polymerase [PARP] inhibitors), at the entering Academic and Community Cancer Research United (ACCRU) institution

• Life expectancy > 6 months

• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

• Patient has score of 0 or 1 on the neurotoxicity evaluation, as determined by the healthcare provider

Exclusion Criteria:

• Previous diagnosis of diabetic neuropathy or peripheral neuropathy from any cause

• Diagnosis of fibromyalgia

• Any prior exposure to neurotoxic chemotherapy

• History of Raynaud?s disease, cryoglobulinemia

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Carle Cancer Center NCI Community Oncology Research Program	Urbana	Illinois	United States	61801
2	Cancer Research Consortium of West Michigan NCORP	Grand Rapids	Michigan	United States	49503
3	Mayo Clinic	Rochester	Minnesota	United States	55905
4	AnMed Health Cancer Center	Anderson	South Carolina	United States	29621
5	Bon Secours Saint Francis Hospital	Charleston	South Carolina	United States	29414
6	Spartanburg Medical Center	Spartanburg	South Carolina	United States	29303
7	Rapid City Regional Hospital	Rapid City	South Dakota	United States	57701
8	Marshfield Clinic	Marshfield	Wisconsin	United States	54449

Sponsors and Collaborators

• Academic and Community Cancer Research United
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Charles Loprinzi, Academic and Community Cancer Research United

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Dec 24, 2015

More Information

Publications

None provided.

• Responsible Party: Academic and Community Cancer Research United
• ClinicalTrials.gov Identifier: NCT02640053
• Other Study ID Numbers: RU221511I; NCI-2015-02014; RU221511I; P30CA015083
• First Posted: Dec 28, 2015
• Last Update Posted: Sep 30, 2019
• Last Verified: Jun 1, 2019

• Additional relevant MeSH terms: Breast Neoplasms; Peripheral Nervous System Diseases; Acute Pain; Paclitaxel; Albumin-Bound Paclitaxel

Study Results

Participant Flow

Recruitment Details	Forty-six (46) participants were enrolled from 13 academic and community practice institutions in the United States between 12/24/2015 and June 16, 2017.
Pre-assignment Detail	There were three patients who withdrew consent (1 cryotherapy, 2 control) and one patient on the cryotherapy arm who was found to be ineligible. All of these 4 participants were excluded from all analyses.

Arm/Group Title	Arm I (Cryotherapy)	Arm II (Control)
Arm/Group Description	Patients receive topical cryotherapy for 15 minutes prior to each paclitaxel dose, during paclitaxel infusion and for 15 minutes following paclitaxel completion. Therapy repeats every week for a planned course of 12 weeks of adjuvant paclitaxel.	Patients receive the standard of care only (paclitaxel at a dose of 80 mg/m2 IV) every week for a planned course of 12 weeks.
Period Title: Overall Study
STARTED	21	21
COMPLETED	17	17
NOT COMPLETED	4	4

Baseline Characteristics

Arm/Group Title	Arm I (Cryotherapy)	Arm II (Control)	Total
Arm/Group Description	Patients receive topical cryotherapy for 15 minutes prior to each paclitaxel dose, during paclitaxel infusion and for 15 minutes following paclitaxel completion. Therapy repeats every week for a planned course of 12 weeks of adjuvant paclitaxel.	Patients receive the standard of care only (paclitaxel at a dose of 80 mg/m2 IV) every week for a planned course of 12 weeks.	Total of all reporting groups
Overall Participants	21	21	42
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	53.0	55.0	53.0
Sex: Female, Male (Count of Participants)
Female	20 95.2%	21 100%	41 97.6%
Male	1 4.8%	0 0%	1 2.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	21 100%	21 100%	42 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	21 100%	21 100%	42 100%
ECOG Performance Status (Count of Participants)
0	18 85.7%	18 85.7%	36 85.7%
1	3 14.3%	3 14.3%	6 14.3%

Outcome Measures

1. Primary Outcome

Title	Area Under the Curve (AUC) EORTC CIPN20 Sensory Neuropathy Subscale Adjusting for Baseline
Description	Average Area Under the Curve per assessment (aAUCpa) of EORTC Chemotherapy-Induced Peripheral Neuropathy Module (EORTC QLQ-CIPN20) Sensory Neuropathy Subscale adjusting for baseline. The EORTC CIPN20 scoring algorithm was used for the sensory (items 31-36, 39, 40 and 48) subscale scores on a 0-100 scale, with higher scores represent fewer symptoms (better QOL). The aAUCpa for the subscale is calculated as the average of each AUC between each sequential assessment from pre-treatment-initiation to the week-12 assessment then subtract the corresponding baseline Sensory Neuropathy subscale score, with positive scores represent symptoms has improved from baseline and negative scores represent symptoms has worsen from baseline.
Time Frame	Up to 12 weeks

Outcome Measure Data

Analysis Population Description

Patients who completed the EORTC QLQ-CIPN20 at pre-treatment-initiation and at least once post-treatment initiation.

Arm/Group Title	Arm I (Cryotherapy)	Arm II (Control)
Arm/Group Description	Patients receive topical cryotherapy for 15 minutes prior to each paclitaxel dose, during paclitaxel infusion and for 15 minutes following paclitaxel completion. Therapy repeats every week for a planned course of 12 weeks of adjuvant paclitaxel.	Patients receive the standard of care only (paclitaxel at a dose of 80 mg/m2 IV) every week for a planned course of 12 weeks.
Measure Participants	19	20
Median (Full Range) [Average(subscale value*assessment)]	-1.4	-4.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (Cryotherapy), Arm II (Control)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.26
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

2. Primary Outcome

Title	Area Under the Curve (AUC) EORTC CIPN20 Tingling Fingers or Hands Item Adjusting for Baseline
Description	Average Area Under the Curve per assessment (aAUCpa) of EORTC Chemotherapy-Induced Peripheral Neuropathy Module (EORTC QLQ-CIPN20) Tingling Fingers or Hands over 12 weeks adjusting for baseline (item 1; "During the past week, did you have tingling fingers or hands?"; 1=Not at all, 2=A little, 3=Quite a bit; and 4=Very much). The reported score was transform into 0-100 scale, with higher scores represent fewer symptoms (better QOL). The aAUCpa for the individual item is calculated as the average of each AUC between each sequential assessment from pre-treatment-initiation to the week-12 assessment then subtract the corresponding baseline score, with positive scores represent symptoms has improved from baseline and negative scores represent symptoms has worsen from baseline.
Time Frame	Up to 12 weeks

Outcome Measure Data

Analysis Population Description

Patients who completed the EORTC QLQ-CIPN20 at pre-treatment-initiation and at least once post-treatment initiation.

Arm/Group Title	Arm I (Cryotherapy)	Arm II (Control)
Arm/Group Description	Patients receive topical cryotherapy for 15 minutes prior to each paclitaxel dose, during paclitaxel infusion and for 15 minutes following paclitaxel completion. Therapy repeats every week for a planned course of 12 weeks of adjuvant paclitaxel.	Patients receive the standard of care only (paclitaxel at a dose of 80 mg/m2 IV) every week for a planned course of 12 weeks.
Measure Participants	19	20
Median (Full Range) [Average(subscale value*assessment)]	0.0	-2.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (Cryotherapy), Arm II (Control)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.72
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

3. Primary Outcome

Title	Area Under the Curve (AUC) EORTC CIPN20 Tingling Toes or Feet Item Adjusting for Baseline
Description	Average Area Under the Curve per assessment (aAUCpa) of EORTC Chemotherapy-Induced Peripheral Neuropathy Module (EORTC QLQ-CIPN20) Tingling Toes or Feet over 12 weeks adjusting for baseline (item 1; "During the past week, did you have tingling toes or feet?"; 1=Not at all, 2=A little, 3=Quite a bit; and 4=Very much). The reported score was transform into 0-100 scale, with higher scores represent fewer symptoms (better QOL). The aAUCpa for the individual item is calculated as the average of each AUC between each sequential assessment from pre-treatment-initiation to the week-12 assessment then subtract the corresponding baseline score, with positive scores represent symptoms has improved from baseline and negative scores represent symptoms has worsen from baseline.
Time Frame	Up to 12 weeks

Outcome Measure Data

Analysis Population Description

Patients who completed the EORTC QLQ-CIPN20 at pre-treatment-initiation and at least once post-treatment initiation.

Arm/Group Title	Arm I (Cryotherapy)	Arm II (Control)
Arm/Group Description	Patients receive topical cryotherapy for 15 minutes prior to each paclitaxel dose, during paclitaxel infusion and for 15 minutes following paclitaxel completion. Therapy repeats every week for a planned course of 12 weeks of adjuvant paclitaxel.	Patients receive the standard of care only (paclitaxel at a dose of 80 mg/m2 IV) every week for a planned course of 12 weeks.
Measure Participants	19	20
Median (Full Range) [Average(subscale value*assessment)]	-1.7	-4.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (Cryotherapy), Arm II (Control)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.39
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

4. Primary Outcome

Title	Area Under the Curve (AUC) EORTC CIPN20 Numbness Fingers or Hands Item Adjusting for Baseline
Description	Average Area Under the Curve per assessment (aAUCpa) of EORTC Chemotherapy-Induced Peripheral Neuropathy Module (EORTC QLQ-CIPN20) Numbness Fingers or Hands over 12 weeks adjusting for baseline (item 1; "During the past week, did you have numbness in your fingers or hands?"; 1=Not at all, 2=A little, 3=Quite a bit; and 4=Very much). The reported score was transform into 0-100 scale, with higher scores represent fewer symptoms (better QOL). The aAUCpa for the individual item is calculated as the average of each AUC between each sequential assessment from pre-treatment-initiation to the week-12 assessment then subtract the corresponding baseline score, with positive scores represent symptoms has improved from baseline and negative scores represent symptoms has worsen from baseline.
Time Frame	Up to 12 weeks

Outcome Measure Data

Analysis Population Description

Patients who completed the EORTC QLQ-CIPN20 at pre-treatment-initiation and at least once post-treatment initiation.

Arm/Group Title	Arm I (Cryotherapy)	Arm II (Control)
Arm/Group Description	Patients receive topical cryotherapy for 15 minutes prior to each paclitaxel dose, during paclitaxel infusion and for 15 minutes following paclitaxel completion. Therapy repeats every week for a planned course of 12 weeks of adjuvant paclitaxel.	Patients receive the standard of care only (paclitaxel at a dose of 80 mg/m2 IV) every week for a planned course of 12 weeks.
Measure Participants	19	20
Median (Full Range) [Average(subscale value*assessment)]	-5.6	-4.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (Cryotherapy), Arm II (Control)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.32
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

5. Primary Outcome

Title	Area Under the Curve (AUC) EORTC CIPN20 Numbness Toes or Feet Item Adjusting for Baseline
Description	Average Area Under the Curve per assessment (aAUCpa) of EORTC Chemotherapy-Induced Peripheral Neuropathy Module (EORTC QLQ-CIPN20) Numbness Toes or Feet over 12 weeks adjusting for baseline (item 1; "During the past week, did you have numbness in your toes or feet?"; 1=Not at all, 2=A little, 3=Quite a bit; and 4=Very much). The reported score was transform into 0-100 scale, with higher scores represent fewer symptoms (better QOL). The aAUCpa for the individual item is calculated as the average of each AUC between each sequential assessment from pre-treatment-initiation to the week-12 assessment then subtract the corresponding baseline score, with positive scores represent symptoms has improved from baseline and negative scores represent symptoms has worsen from baseline.
Time Frame	Up to 12 weeks

Outcome Measure Data

Analysis Population Description

Patients who completed the EORTC QLQ-CIPN20 at pre-treatment-initiation and at least once post-treatment initiation.

Arm/Group Title	Arm I (Cryotherapy)	Arm II (Control)
Arm/Group Description	Patients receive topical cryotherapy for 15 minutes prior to each paclitaxel dose, during paclitaxel infusion and for 15 minutes following paclitaxel completion. Therapy repeats every week for a planned course of 12 weeks of adjuvant paclitaxel.	Patients receive the standard of care only (paclitaxel at a dose of 80 mg/m2 IV) every week for a planned course of 12 weeks.
Measure Participants	19	20
Median (Full Range) [Average(subscale value*assessment)]	0.0	-3.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (Cryotherapy), Arm II (Control)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.41
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

6. Primary Outcome

Title	Area Under the Curve (AUC) EORTC CIPN20 Shooting/Burning Pain in Fingers or Hands Item Adjusting for Baseline
Description	Average Area Under the Curve per assessment (aAUCpa) of EORTC Chemotherapy-Induced Peripheral Neuropathy Module (EORTC QLQ-CIPN20) Shooting/Burning Pain in Fingers or Hands over 12 weeks adjusting for baseline (item 1; "During the past week, did you have shooting or burning pain in your fingers or hands?"; 1=Not at all, 2=A little, 3=Quite a bit; and 4=Very much). The reported score was transform into 0-100 scale, with higher scores represent fewer symptoms (better QOL). The aAUCpa for the individual item is calculated as the average of each AUC between each sequential assessment from pre-treatment-initiation to the week-12 assessment then subtract the corresponding baseline score, with positive scores represent symptoms has improved from baseline and negative scores represent symptoms has worsen from baseline.
Time Frame	Up to 12 weeks

Outcome Measure Data

Analysis Population Description

Patients who completed the EORTC QLQ-CIPN20 at pre-treatment-initiation and at least once post-treatment initiation.

Arm/Group Title	Arm I (Cryotherapy)	Arm II (Control)
Arm/Group Description	Patients receive topical cryotherapy for 15 minutes prior to each paclitaxel dose, during paclitaxel infusion and for 15 minutes following paclitaxel completion. Therapy repeats every week for a planned course of 12 weeks of adjuvant paclitaxel.	Patients receive the standard of care only (paclitaxel at a dose of 80 mg/m2 IV) every week for a planned course of 12 weeks.
Measure Participants	19	20
Median (Full Range) [Average(subscale value*assessment)]	0.0	0.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (Cryotherapy), Arm II (Control)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.76
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

7. Primary Outcome

Title	Area Under the Curve (AUC) EORTC CIPN20 Shooting/Burning Pain in Toes or Feet Item Adjusting for Baseline
Description	Average Area Under the Curve per assessment (aAUCpa) of EORTC Chemotherapy-Induced Peripheral Neuropathy Module (EORTC QLQ-CIPN20) Shooting/Burning Pain in Toes or Feet over 12 weeks adjusting for baseline (item 1; "During the past week, did you have shooting or burning pain in your Toes or Feet?"; 1=Not at all, 2=A little, 3=Quite a bit; and 4=Very much). The reported score was transform into 0-100 scale, with higher scores represent fewer symptoms (better QOL). The aAUCpa for the individual item is calculated as the average of each AUC between each sequential assessment from pre-treatment-initiation to the week-12 assessment then subtract the corresponding baseline score, with positive scores represent symptoms has improved from baseline and negative scores represent symptoms has worsen from baseline.
Time Frame	Up to 12 weeks

Outcome Measure Data

Analysis Population Description

Patients who completed the EORTC QLQ-CIPN20 at pre-treatment-initiation and at least once post-treatment initiation.

Arm/Group Title	Arm I (Cryotherapy)	Arm II (Control)
Arm/Group Description	Patients receive topical cryotherapy for 15 minutes prior to each paclitaxel dose, during paclitaxel infusion and for 15 minutes following paclitaxel completion. Therapy repeats every week for a planned course of 12 weeks of adjuvant paclitaxel.	Patients receive the standard of care only (paclitaxel at a dose of 80 mg/m2 IV) every week for a planned course of 12 weeks.
Measure Participants	19	20
Median (Full Range) [Average(subscale value*assessment)]	0.0	0.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (Cryotherapy), Arm II (Control)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.62
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

8. Secondary Outcome

Title	Area Under the Curve (AUC) Per Assessment (aAUCpa) of Worst Pain (Item 1 on the Daily Post-Paclitaxel Questionnaire)
Description	Average Area Under the Curve (AUC) per assessment (aAUCpa) of worst pain (item 1 on the Daily Post-Paclitaxel Questionnaire; "Please rate any aches/pain that are new since your last dose of paclitaxel, and that you think might be related to your chemotherapy treatment, by circling ONE number that best describes your aches/pain at its WORST in the last 24 hours.") over 1 week. Scores are reported on a 0-100 scale, where 100=better outcome quality of life (QOL). The aAUCpa is the average of each AUC between each sequential assessment from day 2 through 7 following paclitaxel.
Time Frame	1 week

Outcome Measure Data

Analysis Population Description

Patients who completed the Daily Post-Paclitaxel Questionnaire over the first week of paclitaxel were included in this analysis.

Arm/Group Title	Arm I (Cryotherapy)	Arm II (Control)
Arm/Group Description	Patients receive topical cryotherapy for 15 minutes prior to each paclitaxel dose, during paclitaxel infusion and for 15 minutes following paclitaxel completion. Therapy repeats every week for a planned course of 12 weeks of adjuvant paclitaxel.	Patients receive the standard of care only (paclitaxel at a dose of 80 mg/m2 IV) every week for a planned course of 12 weeks.
Measure Participants	19	19
Median (Full Range) [Average(subscale value*assessment)]	95.0	96.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (Cryotherapy), Arm II (Control)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.67
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Adverse Events

Time Frame	Up to 12 weeks
Adverse Event Reporting Description	The descriptions & grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting. Each CTCAE term in the current version is a unique representation of a specific event used for medical documentation & scientific analysis & is a single MedDRA Lowest Level Term (LLT).
Arm/Group Title	Arm I (Cryotherapy)		Arm II (Control)
Arm/Group Description	Patients receive topical cryotherapy for 15 minutes prior to each paclitaxel dose, during paclitaxel infusion and for 15 minutes following paclitaxel completion. Therapy repeats every week for a planned course of 12 weeks of adjuvant paclitaxel.		Patients receive the standard of care only (paclitaxel at a dose of 80 mg/m2 IV) every week for a planned course of 12 weeks.
All Cause Mortality
	Arm I (Cryotherapy)		Arm II (Control)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/21 (0%)		0/21 (0%)
Serious Adverse Events
	Arm I (Cryotherapy)		Arm II (Control)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/21 (0%)		1/21 (4.8%)
Infections and infestations
Lung infection	0/21 (0%)	0	1/21 (4.8%)	1
Respiratory, thoracic and mediastinal disorders
Respiratory failure	0/21 (0%)	0	1/21 (4.8%)	1
Other (Not Including Serious) Adverse Events
	Arm I (Cryotherapy)		Arm II (Control)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/21 (19%)		9/21 (42.9%)
Cardiac disorders
Cardiac disorders - Other, specify	1/21 (4.8%)	1	0/21 (0%)	0
Supraventricular tachycardia	0/21 (0%)	0	1/21 (4.8%)	1
Gastrointestinal disorders
Constipation	0/21 (0%)	0	1/21 (4.8%)	4
Diarrhea	0/21 (0%)	0	2/21 (9.5%)	4
General disorders
Fatigue	0/21 (0%)	0	3/21 (14.3%)	8
Investigations
Alanine aminotransferase increased	0/21 (0%)	0	1/21 (4.8%)	2
Lymphocyte count decreased	3/21 (14.3%)	4	2/21 (9.5%)	12
Neutrophil count decreased	0/21 (0%)	0	2/21 (9.5%)	2
White blood cell decreased	0/21 (0%)	0	1/21 (4.8%)	1
Musculoskeletal and connective tissue disorders
Back pain	0/21 (0%)	0	1/21 (4.8%)	1
Pain in extremity	1/21 (4.8%)	1	0/21 (0%)	0
Nervous system disorders
Peripheral motor neuropathy	0/21 (0%)	0	1/21 (4.8%)	1
Peripheral sensory neuropathy	0/21 (0%)	0	1/21 (4.8%)	1
Syncope	0/21 (0%)	0	1/21 (4.8%)	1
Psychiatric disorders
Insomnia	0/21 (0%)	0	1/21 (4.8%)	1
Skin and subcutaneous tissue disorders
Alopecia	0/21 (0%)	0	2/21 (9.5%)	21

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.