Hand-Foot Skin Reaction (HFSR), Solid Tumor
Conditions
Keywords
Solid Tumor, Hand-Foot Skin Reaction (HFSR)
Brief summary
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).
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
Interventions
DRUGTopical Tazarotene
This medicine works by making the skin less inflamed and reducing the thickness and pain from lesions of the skin
OTHERPlacebo
A substance that has no therapeutic effect, used as a control in testing new drugs
Sponsors
Bayer
Dana-Farber Cancer Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Grade 2 or Higher Hand-Foot Skin Reaction (HFSR) Rate | Up to 8 weeks | 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. |
| All Grade Hand-Foot Skin Reaction (HFSR) Rate | Up to 8 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in HFS-14 Score From Baseline to Day 56 | At baseline and at 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. |
| Change in Perceived Stress Scale (PSS) From Baseline to Day 56 | at baseline and 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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
Topical Tazarotene: This medicine works by making the skin less inflamed and reducing the thickness and pain from lesions of the skin | 5 |
| 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.
Placebo: A substance that has no therapeutic effect, used as a control in testing new drugs | 3 |
| Total | 8 |
Baseline characteristics
| Characteristic | Topical Tazarotene 0.1% Gel Plus BPS | Placebo Gel Plus BPS | Total |
|---|---|---|---|
| Age, Continuous | 61.6 years STANDARD_DEVIATION 11.1 | 44.0 years STANDARD_DEVIATION 18 | 55.0 years STANDARD_DEVIATION 15.7 |
| Body Mass Index (BMI) | 23.3 kg/m^2 STANDARD_DEVIATION 3.5 | 30.4 kg/m^2 STANDARD_DEVIATION 7.1 | 26 kg/m^2 STANDARD_DEVIATION 5.9 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 3 Participants | 1 Participants | 4 Participants |
| Region of Enrollment United States | 5 participants | 3 participants | 8 participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 3 Participants |
| Sex: Female, Male Male | 3 Participants | 2 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 3 |
| other Total, other adverse events | 5 / 5 | 3 / 3 |
| serious Total, serious adverse events | 1 / 5 | 0 / 3 |
Outcome results
Primary
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.
Time frame: Up to 8 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Topical Tazarotene 0.1% Gel Plus BPS | All Grade Hand-Foot Skin Reaction (HFSR) Rate | 100 percentage of participants |
| Placebo Gel Plus BPS | All Grade Hand-Foot Skin Reaction (HFSR) Rate | 100 percentage of participants |
Primary
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.
Time frame: Up to 8 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Topical Tazarotene 0.1% Gel Plus BPS | Grade 2 or Higher Hand-Foot Skin Reaction (HFSR) Rate | 20 percent of participants |
| Placebo Gel Plus BPS | Grade 2 or Higher Hand-Foot Skin Reaction (HFSR) Rate | 33.33 percent of participants |
Secondary
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.
Time frame: At baseline and at day 56.
Population: Trial was terminated at enrollment of 8 participants including n=3 on the placebo arm; the PRO evaluable sample for the placebo arm is not provided due to patient privacy.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Topical Tazarotene 0.1% Gel Plus BPS | Change in HFS-14 Score From Baseline to Day 56 | 1 units on a scale |
Secondary
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.
Time frame: at baseline and day 56
Population: Trial was terminated at enrollment of 8 participants including n=3 on the placebo arm; the PRO evaluable sample for the placebo arm is not provided due to patient privacy.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Topical Tazarotene 0.1% Gel Plus BPS | Change in Perceived Stress Scale (PSS) From Baseline to Day 56 | 7.5 units on a scale |