Clinical trial NCT05642611: Comparing Cooling and/or Compression Approaches of Limbs for Prevention of Chemotherapy-Induced Peripheral Neuropathy
Official title: Ice Compress: Randomized Trial of Limb Cryocompression Versus Continuous Compression Versus Low Cyclic Compression for the Prevention of Taxane-Induced Peripheral Neuropathy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Malignant Solid Neoplasm
Lead sponsor: SWOG Cancer Research Network
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2022-12-08
Enrollment: 777
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This phase III trial compares the effect of 3 study approaches in preventing chemotherapy-induced peripheral neuropathy: 1) cryocompression, 2) continuous compression, and 3) low cyclic compression. Taxane chemotherapy drugs, such as paclitaxel or docetaxel, can cause a nerve disorder called peripheral neuropathy, which can cause numbness, tingling, or pain in the arms and legs. The 3 study approaches will use a device, called the Paxman Limb Cryocompression System, made of wraps that cool and/or compress the arms and legs. This study may help researchers determine if any of the study approaches are able to prevent taxane chemotherapy from causing peripheral neuropathy.

Detailed description: PRIMARY OBJECTIVE:

I. To compare the proportion of participants who develop clinically meaningful chemotherapy induced peripheral neuropathy (CIPN) at 12 weeks, in participants treated with taxane-based chemotherapy randomized to cryocompression therapy versus continuous compression therapy versus low cyclic compression therapy.

SECONDARY OBJECTIVES:

I. To compare trajectories over time (6, 12, 24, and 52 weeks) by intervention study arm in clinically meaningful CIPN.

II. To compare mean European Organization for Research and Treatment of Cancer Chemotherapy-Induced Peripheral Neuropathy 20 (EORTC-CIPN-20) sensory neuropathy subscale scores at 12 weeks by intervention study arm.

III. To compare differences by intervention study arm at 12 weeks in changes from baseline in objective sensory and motor function tests (Neuropen, tuning fork, Timed Get Up and Go test).

IV. To compare the proportion of participants who develop clinically meaningful CIPN at 12 weeks in a sensitivity analysis with dropouts treated as failures.

V. To compare rates of adverse events related to study device at 12 weeks (including cold intolerance, skin changes, other adverse events \[AEs\] as assessed by Common Terminology Criteria for Adverse Events \[CTCAE\]) between the three interventions.

ADDITIONAL OBJECTIVES:

I. To compare the proportion of participants who develop clinically meaningful CIPN separately at weeks 6, 24, and 52.

II. To compare the proportion of participants who develop clinically meaningful CIPN at week 12 with additional covariate adjustment for age and body mass index (BMI).

III. To compare differences by intervention study arm at 12 weeks in mean EORTC CIPN-20 motor subscale score and autonomic subscale score, and in mean individual Patient-Reported Outcomes Measurement Information System (PROMIS)-29 domain (Physical Functioning, Anxiety, Depression, Fatigue, Sleep Disturbance, Social Functioning, Pain Interference, and Pain Intensity) scores.

IV. To compare trajectories over time (6, 12, 24, and 52 weeks) by intervention study arm in mean EORTC CIPN-20 sensory neuropathy subscale score, motor subscale score, and autonomic subscale score; and in mean PROMIS-29 individual domains (Physical Functioning, Anxiety, Depression, Fatigue, Sleep Disturbance, Social Functioning, Pain Interference, and Pain Intensity) scores; and in changes in objective sensory and motor function tests (Neuropen, tuning fork, Timed Get Up and Go test).

V. To evaluate the differences by intervention study arm in proportion of participants who develop clinically meaningful CIPN at 12 weeks by chemotherapy regimen.

VI. To assess the effect of the intervention in reducing CIPN occurring in the upper extremities and, separately, in the lower extremities.

VII. To explore the relationship between duration of intervention received at the prescribed level and outcome, analogous to a dose-delivered analysis in a treatment trial.

VIII. To compare rates by study arm of CTCAE Grade 2 or higher sensory and motor neuropathy at 12 weeks.

IX. To evaluate tolerability of cryocompression compared to continuous compression therapy and low cyclic compression therapy, as assessed by rate of temperature and/or pressure adjustments, interruptions, and early discontinuation of the device.

X. To determine participant satisfaction of cryocompression compared to continuous compression therapy and low cyclic compression therapy, assessed by patient questionnaire.

XI. To compare taxane dose-reductions, treatment delays/discontinuation due to CIPN, and relative taxane dose intensity and total taxane dose received, between intervention study arms.

XII. To evaluate differences of intervention effect by sex, race, and ethnicity.

XIII. To confirm pretreatment biomarkers of CIPN risk (vitamin D) and on-treatment biomarker changes indicative of CIPN severity (Neurofilament light chain, NFL) as well as additional biomarkers of interest generated in S1714 for validation.

BANKING OBJECTIVE:

I. To bank specimens for future correlative studies.

OUTLINE: Patients are randomized to 1 of 3 arms.

ARM 1: Patients undergo cryocompression (cooling plus moderate and low pressure to the arms and legs) for 30-minutes pre-taxane chemotherapy infusion, during taxane chemotherapy infusion, and for 30 minutes after completion of each taxane infusion. Patients may also undergo collection of blood, serum and plasma samples during screening and on study.

ARM 2: Patients undergo continuous compression (moderate, steady pressure to the arms and legs) for 30-minutes pre-taxane chemotherapy infusion, during taxane chemotherapy infusion, and for 30 minutes after completion of each taxane infusion. Patients may also undergo collection of blood, serum and plasma samples during screening and on study.

ARM 3: Patients undergo low cyclic compression (low pressure that comes and goes to the arms and legs) for 30-minutes pre-taxane chemotherapy infusion, during taxane chemotherapy infusion, and for 30 minutes after completion of each taxane infusion. Patients may also undergo collection of blood, serum and plasma samples during screening and on study.

Eligibility criteria: Inclusion Criteria:

* Participants must have a diagnosis of a solid tumor malignancy.
* Participants must be planning to begin neoadjuvant or adjuvant therapy with one of the protocol-specified chemotherapy regimens below for a solid tumor malignancy within 3 calendar days after randomization.

  * Weekly paclitaxel x 12 consecutive weeks
  * Weekly paclitaxel x 12 consecutive weeks + carboplatin (weekly x 12 consecutive weeks or every 3 weeks x 4 consecutive cycles)
  * Paclitaxel + carboplatin every 3 weeks x 6 consecutive cycles without chemotherapy pause for surgery
  * Docetaxel + carboplatin every 3 weeks x 6 consecutive cycles without chemotherapy pause for surgery NOTE: For any of the protocol-specified chemotherapy regimens, concurrent targeted therapy with biologic therapy is allowed. Pembrolizumab (or other immune checkpoint inhibitors), trastuzumab and/or pertuzumab, or bevacizumab are allowed.
* Participant must be \>= 18 years old.
* Participants must be offered the opportunity to participate in specimen banking. With participant consent, specimens must be collected and submitted via the Southwest Oncology Group (SWOG) Specimen Tracking System.
* Participants must be able to complete Patient-Reported Outcome (PRO) questionnaires in English or Spanish.
* Participants must 1) agree to complete PROs at all scheduled assessments, and 2) complete the baseline PRO questionnaires within 14 days prior to randomization
* Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines.

For participants with impaired decision-making capabilities, legally authorized representatives may sign and give informed consent on behalf of study participants in accordance with applicable federal, local, and Central Institutional Review Board (CIRB) regulations.

Exclusion Criteria:

* Participants must not have a history of skin or limb metastases.
* Participants must not have previously received neurotoxic chemotherapy for any reason (e.g., taxanes, platinum agents, vinca alkaloids, or bortezomib).
* Participants must not have pre-existing clinical peripheral neuropathy from any cause.
* Participants must not have a history of Raynaud's phenomenon, cold agglutinin disease, cryoglobulinemia, cryofibrinogenemia, post-traumatic cold dystrophy, or peripheral arterial ischemia.
* Participants must not have any open skin wounds or ulcers of the limbs at the time of randomization.

Primary outcomes:
measure: Occurrence of clinically meaningful chemotherapy induced peripheral neuropathy (CIPN) (binary outcome: yes vs. no)
timeFrame: At the 12-week assessment after randomization
Secondary outcomes:
measure: Mean sensory neuropathy scores
timeFrame: At 12 weeks
measure: Dropouts
timeFrame: Prior to the week 12 assessment
measure: Trajectories over time
timeFrame: 6, 12, 24, and 52 weeks
measure: Rates of adverse events
timeFrame: At 12 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham Cancer Center
state: Alabama
city: Martinez
country: United States
facility: Contra Costa Regional Medical Center
state: California
city: Atlanta
country: United States
facility: Emory University Hospital/Winship Cancer Institute
state: Georgia
city: Honolulu
country: United States
facility: Kapiolani Medical Center for Women and Children
state: Hawaii
city: Kansas City
country: United States
facility: University of Kansas Cancer Center
state: Kansas
city: Overland Park
country: United States
facility: University of Kansas Hospital-Indian Creek Campus
state: Kansas
city: Westwood
country: United States
facility: University of Kansas Hospital-Westwood Cancer Center
state: Kansas
city: Lexington
country: United States
facility: Baptist Health Lexington
state: Kentucky
city: Clinton Township
country: United States
facility: Henry Ford Macomb Hospital-Clinton Township
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Grand Rapids
country: United States
facility: Corewell Health Grand Rapids Hospitals - Butterworth Hospital
state: Michigan
city: Paramus
country: United States
facility: The Valley Hospital - Luckow Pavilion
state: New Jersey
city: Ridgewood
country: United States
facility: Valley Health System Ridgewood Campus
state: New Jersey
city: Albuquerque
country: United States
facility: University of New Mexico Cancer Center
state: New Mexico
city: New York
country: United States
facility: NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
state: New York
city: Syracuse
country: United States
facility: State University of New York Upstate Medical University
state: New York
city: Gastonia
country: United States
facility: CaroMont Regional Medical Center
state: North Carolina
city: Greensboro
country: United States
facility: Cone Health Cancer Center
state: North Carolina
city: Hendersonville
country: United States
facility: Margaret R Pardee Memorial Hospital
state: North Carolina
city: Cincinnati
country: United States
facility: Good Samaritan Hospital - Cincinnati
state: Ohio
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Florence
country: United States
facility: McLeod Regional Medical Center
state: South Carolina
city: Gaffney
country: United States
facility: Gibbs Cancer Center-Gaffney
state: South Carolina
city: Greer
country: United States
facility: Gibbs Cancer Center-Pelham
state: South Carolina
city: Spartanburg
country: United States
facility: Spartanburg Medical Center
state: South Carolina
city: Union
country: United States
facility: MGC Hematology Oncology-Union
state: South Carolina
city: Houston
country: United States
facility: Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
state: Texas
city: Midlothian
country: United States
facility: Bon Secours Saint Francis Medical Center
state: Virginia
city: Seattle
country: United States
facility: University of Washington Medical Center - Montlake
state: Washington
Study officials:
affiliation: SWOG - Columbia University
name: Melissa K Accordino
role: PRINCIPAL_INVESTIGATOR
affiliation: NRG - University of Washington
name: Katherine Pennington, MD
role: PRINCIPAL_INVESTIGATOR
References: