Topical Tazarotene Vs Placebo In Hand-Foot-Skin Reactions

A Phase II Randomized Double-Blind Trial of Topical Tazarotene 0.1% Gel Versus Placebo Gel for the Prevention of Regorafenib-Induced Hand-Foot-Skin Reaction

This research is studying the preventative use of topical 0.1% tazarotene gel daily in addition to best practice standards to reduce the development of hand-foot skin reaction (HFSR).

Study Overview

• Status: Terminated
• Conditions: Solid Tumor; Hand-Foot Skin Reaction (HFSR)
• Intervention / Treatment: Drug: Topical Tazarotene; Other: Placebo

Detailed Description

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific disease. "Investigational" means that the drug is being studied.

The U.S. Food and Drug Administration (FDA) has not approved tazarotene for specifically for hand-foot skin reaction but it has been approved for other uses.

In this research study, the investigators are:

-aiming to determine if the use of tazarotene gel daily, in addition to best practice standards:

• reduces the development of HFSR.
• decreases modification of regorafenib dose due to HFSR
• improves health-related quality of life associated with HFSR
• decreases stress associated with HFSR

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana Farber Cancer Institute

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Participants must have histologically or cytologically confirmed solid tumors with a plan to initiate regorafenib, or having started regorafenib in the last 48 hours, via dose escalation protocol describe in the ReDOS study in CRC. The ReDOS study recommends this dose escalation of regorafenib:80mg daily x 1 week, 120mg daily x 1 week, 160mg daily times one week, off week, then 160mg daily goal, or maximum tolerated dose thereafter. This is not a separate study; this is the current standard of care for regorafenib dosing. In addition, to compare across the cohorts, patients must be ambulatory with full use of all 4 distal extremities.
• Age ≥ 18
• ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A)
• Participants must have sufficient organ and marrow function in the opinion of the treating investigator. This can be based on lab reports from an outside facility.
• Women of child-bearing potential (WOCBP) and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation Tazarotene is known to be teratogenic, although the dose required with topical application to affect the developing human fetus is unknown. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of administration.
• Women of child-bearing potential (WOCBP) must have a negative serum pregnancy test.
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Regorafenib use in combination with another TKI (unless regorafenib was started in the last 48 hours)
• Pregnancy or non-compliance with contraception (4 weeks before, during and for at least 3 ovulatory cycles after treatment cessation). Pregnant women are excluded from this study because tazarotene is category X with the potential for teratogenic or abortifacient effects.
• Nursing or lactating: Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with tazarotene, breastfeeding should be discontinued if the mother is treated.
• A history of hypervitaminosis A
• Other systemic retinoids needed for another condition (ie. Isotretinoin for inflammatory acne, acitretin for psoriasis, bexarotene for CTCL).
• Need for treatment dose systemic steroids or systemic immunosuppressive agents (i.e., for autoimmune disease or cerebral edema) at the time of enrolment
• Psoriasis or other autoimmune disease requiring skin directed or systemic therapy known to impact keratinocyte proliferation (UV therapy to the hands or feet, TNF inhibitors, etc).
• Active skin disease of the hands or feet with redness, scaling or blisters prior to enrolment
• Participants who have had any systemic chemotherapy or immunotherapy within 4 weeks prior to entering the study AND who have not recovered from adverse events on the hands and feet due to the agents administered.
• Participants who are receiving any other investigational agents to treat HFSR.
• Uncontrolled intercurrent illness including, but not limited to, uncontrolled lower extremity edema, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Topical Tazarotene 0.1% Gel Plus BPS; Pharmacy teaching call; DFCI approved teaching sheets will be provided; 20% urea applied to the palms and soles in the morning + tazarotene 0.1% gel, applied to the palms and soles nightly	Drug: Topical Tazarotene; This medicine works by making the skin less inflamed and reducing the thickness and pain from lesions of the skin; Other Names: Tazorac
Placebo Comparator: Placebo Gel Plus BPS; A substance that has no therapeutic effect, used as a control in testing new drugs; Pharmacy teaching call; DFCI approved teaching sheets will be provided; 20% urea applied to the palms and soles in the morning with placebo gel applied in the evening.	Other: Placebo; A substance that has no therapeutic effect, used as a control in testing new drugs

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Grade 2 or Higher Hand-Foot Skin Reaction (HFSR) Rate	Grade 2 or higher hand-foot skin reaction (HFSR) Rate defined as the percentage of patients in each arm who develop grade-2 or higher HFSR within the first 8 weeks of protocol therapy. Measured via examination by a Dermatology Provider and grading according to CTCAE version 5.	Up to 8 weeks
All Grade Hand-Foot Skin Reaction (HFSR) Rate	Any grade hand-foot skin reaction (HFSR) Rate defined as the percentage of patients in each arm who develop HFSR within the first 8 weeks of protocol therapy. Measured via examination by a Dermatology Provider and grading according to CTCAE version 5.	Up to 8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in HFS-14 Score From Baseline to Day 56	HFS-14 is a specific quality of life scale developed for patients suffering from Hand-Foot Syndrome. It involves 14 questions per protocol Appendix D. Answers are ranked based on the subscripts listed from the level that affect quality of life much to less. Answers are ranked based on the subscripts from survey to not affect life quality (1-4). Maximum score is 44, and minimum score is 14. Change measured from baseline and day 56. Higher score means worse situation.	At baseline and at day 56.
Change in Perceived Stress Scale (PSS) From Baseline to Day 56	PSS is a classic stress assessment instrument that helping understand how different situations affect patients' feelings and perceived stress. Patients answer 10 questions defined in protocol appendix D. Answers are ranked 0-4. The higher the overall scores indicate higher perceived stress. Score range is from 0 to 40. Higher score means more stressful. Change measured at baseline and day 56.	at baseline and day 56

Collaborators and Investigators

• Sponsor: Dana-Farber Cancer Institute
• Collaborators: Bayer
• Investigators: Principal Investigator: Nicole LeBoeuf, MD, Dana-Farber Cancer Institute

Study record dates

Study Major Dates

• Study Start (Actual): December 30, 2019
• Primary Completion (Actual): June 12, 2021
• Study Completion (Actual): July 14, 2022

Study Registration Dates

• First Submitted: June 5, 2019
• First Submitted That Met QC Criteria: August 26, 2019
• First Posted (Actual): August 28, 2019

Study Record Updates

• Last Update Posted (Estimated): February 7, 2024
• Last Update Submitted That Met QC Criteria: February 5, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Solid Tumor; Hand-Foot Skin Reaction (HFSR)
• Additional Relevant MeSH Terms: Dermatologic Agents; Keratolytic Agents; Tazarotene
• Other Study ID Numbers: 19-099

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: [contact information for Sponsor Investigator or designee]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research
• IPD Sharing Time Frame: Data can be shared no earlier than 1 year following the date of publication
• IPD Sharing Access Criteria: BCH - Contact the Technology & Innovation Development Office at www.childrensinnovations.org or email TIDO@childrens.harvard.edu BIDMC - Contact the Beth Israel Deaconess Medical Center Technology Ventures Office at tvo@bidmc.harvard.edu BWH - Contact the Partners Innovations team at http://www.partners.org/innovation DFCI - Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu MGH - Contact the Partners Innovations team at http://www.partners.org/innovation
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No