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

• ClinicalTrials.gov Identifier: NCT02640053
• Recruitment Status: Completed
• First Posted: December 28, 2015
• Results First Posted: October 5, 2018
• Last Update Posted: September 30, 2019
• Sponsor: Academic and Community Cancer Research United
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Academic and Community Cancer Research United

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	Not Applicable

Detailed Description:

PRIMARY OBJECTIVES:

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

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

III. 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 (Clinical Trial)
• 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: December 23, 2015
• Actual Primary Completion Date: September 5, 2017
• Actual Study Completion Date: October 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 Name: 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 Name: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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

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

Criteria

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

United States, Illinois

Carle Cancer Center NCI Community Oncology Research Program

Urbana, Illinois, United States, 61801

United States, Michigan

Cancer Research Consortium of West Michigan NCORP

Grand Rapids, Michigan, United States, 49503

United States, Minnesota

Mayo Clinic

Rochester, Minnesota, United States, 55905

United States, South Carolina

AnMed Health Cancer Center

Anderson, South Carolina, United States, 29621

Bon Secours Saint Francis Hospital

Charleston, South Carolina, United States, 29414

Spartanburg Medical Center

Spartanburg, South Carolina, United States, 29303

United States, South Dakota

Rapid City Regional Hospital

Rapid City, South Dakota, United States, 57701

United States, Wisconsin

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)

Documents provided by Academic and Community Cancer Research United:

Study Protocol and Statistical Analysis Plan  [PDF] December 24, 2015

More Information

• Responsible Party: Academic and Community Cancer Research United
• ClinicalTrials.gov Identifier: NCT02640053
• Other Study ID Numbers: RU221511I; NCI-2015-02014 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); RU221511I ( Other Identifier: Academic and Community Cancer Research United ); P30CA015083 ( U.S. NIH Grant/Contract )
• First Posted: December 28, 2015
• Results First Posted: October 5, 2018
• Last Update Posted: September 30, 2019
• Last Verified: June 2019

Additional relevant MeSH terms:

Breast Neoplasms; Peripheral Nervous System Diseases; Acute Pain; Neuromuscular Diseases; Nervous System Diseases; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Pain; Neurologic Manifestations; Paclitaxel; Albumin-Bound Paclitaxel; Antineoplastic Agents, Phytogenic; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action