The goal of this clinical trial is to learn about HT-001 Topical Gel for treatment of EGFR inhibitor-induced skin toxicities. The main questions it aims to answer are: * Determine the therapeutic effect of HT-001 for treatment of patients who develop acneiform rash undergoing Epidermal Growth Factor inhibitor (EGFRI) therapy using the acneiform rash investigator's global assessment scale \[ARIGA\] * Evaluate the safety of HT-001 during treatment Participants will apply HT-001 Gel once per day for 6 weeks, during which the effect on treating acneiform rash or other skin disorders induced by EGFRI therapy will be evaluated using different assessment tools to measure severity of rash, pain, and itching (pruritus), as well as the change in quality of life. The study will be completed in 2 periods: the first period is open-label (unblinded) and all patients will receive HT-001 topical gel with the active ingredient; the second period is blinded and patients will be randomized to receive one of three concentrations of HT-001 or placebo. Researchers will compare HT-001 to the placebo in the second period to see if HT-001 provides a significant treatment effect.
This is a randomized, double-blind, placebo-controlled, multi-center Phase 2a dose-ranging study to evaluate the efficacy, safety, and tolerability of HT-001 for treatment of EGFRI-induced skin toxicity. The study will include adult patients (≥ 18 years of age) scheduled to receive initial or repeat EGFRI therapy. The study will be conducted in 2 periods: Part 1, an open-label cohort consisting of 12 patients to measure pharmacokinetics of HT 001 gel followed by Part 2, a randomized, parallel arm study comparing 3 dose strengths of HT-001 gel to placebo (HT 001 vehicle). Patients in the randomized cohorts will be randomly assigned to 1 of the 4 treatment arms in a 2:2:2:1 ratio (active groups = 2: placebo = 1). All patients in both open-label and blinded cohorts will apply the study drug once a day to each area affected with cutaneous toxicity up to 30% body surface area (BSA) involvement, inclusive of skin, scalp, and nails. The goal of the study is to determine the minimum efficacious dose strength(s) for further investigation. The dose effect, together with the application site safety assessments, and therapeutic effects based on the primary and secondary endpoints will be evaluated.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
SUPPORTIVE_CARE
Masking
QUADRUPLE
Enrollment
152
Topical gel, 2% active
Topical gel, 1% active
Topical gel, 0.5% active
Topical gel, vehicle gel
UCI Health - CIACC
Irvine, California, United States
RECRUITINGUC Irvine - Chao Family Cancer Center
Orange, California, United States
RECRUITINGThe George Washington University Medical Faculty Associates
Washington D.C., District of Columbia, United States
RECRUITINGDana Farber Cancer Institute
Boston, Massachusetts, United States
RECRUITINGNYU Langone Health
Mineola, New York, United States
RECRUITINGNorthwell Physician Partners Dermatology
New Hyde Park, New York, United States
RECRUITINGMontefiore Medical Center
The Bronx, New York, United States
RECRUITINGMD Anderson Cancer Center
Houston, Texas, United States
RECRUITINGAcneiform Rash Investigator's Global Assessment Scale [ARIGA ]
Proportion of patients with a grade ≤ 1 based on the Acneiform Rash Investigator's Global Assessment \[ARIGA\] Scale; novel 5-point scale 0-4 with score of 0 is clear and grade 4 being most severe
Time frame: 6 weeks
Pharmacokinetics of HT-001 applied topically [Cohort 1] - Area Under the Curve (AUC)
Characterize pharmacokinetics of HT-001 parameters including: measured drug concentrations above the lower limit of quantitation, number of patients with measurable systemic exposure; if data allow - area under the curve (AUC)
Time frame: Day 1 and Day 42
Pharmacokinetics of HT-001 applied topically [Cohort 1] - Peak Plasma Concentration (Cmax)
Characterize pharmacokinetics of HT-001 parameters including: maximum (or peak) serum concentration (Cmax)
Time frame: Day 1 and Day 42
Pruritus Numeric Rating Scale (NRS)
Change from Baseline in Pruritus Numeric Rating Scale (average itch and worst itch); The numerical scale is ranked from 0 ("no itch") to 10 ("worst imaginable itch").
Time frame: 3 weeks and 6 weeks
Pain Numeric Rating Scale
Change from Baseline in pain based on a 11-point NRS (where "0" indicates "no pain", "5" indicates "moderate pain" and "10" indicates "worst pain imaginable")
Time frame: 3 weeks and 6 weeks
Change in acneiform rash severity
Change from Baseline in acneiform rash grade based on the Acneiform Rash Investigator's Global Assessment Scale \[ARIGA\]; novel 5-point scale 0-4 with score of 0 is clear and grade 4 being most severe
Time frame: 3 weeks and 6 weeks
Time to improvement
Time to improvement in at least one grade using the Acneiform Rash Investigator's Global Assessment Scale \[ARIGA \] for acneiform rash; novel 5-point scale 0-4 with score of 0 is clear and grade 4 being most severe
Time frame: 6 weeks Day 1- Day 42
Time to rescue therapy
Time to topical rescue therapy treatment after initiation of HT-001
Time frame: Treatment Day 1- Day 42
EGFR Inhibitor dose reduction or discontinuation
Proportion of patients with EGFRI dose reduction or discontinuation during the 6-week treatment period
Time frame: Treatment Day 1- Day 42
Safety and tolerability of HT-001
Incidence of treatment-emergent adverse events and treatment-emergent serious adverse events
Time frame: screening, Day 1 - 42, follow-up (Day 56)
Modified Draize Scale
Assessment of skin irritation through measurement of cutaneous signs of erythema (score 0-3; 3 is most severe) and edema (add 0.5 if present)
Time frame: Day 1, 7, 21, 35, 42, 56
Physical Examination
full physical examination will include examination of general appearance, skin, neck (including thyroid), eyes, ears, nose, throat, heart, lungs, abdomen, lymph nodes, extremities, and nervous system. An AE form must be completed for all changes identified as clinically noteworthy.
Time frame: Day 1, 7, 21, 35, 42, 56
Height
Height recorded in inches
Time frame: Screening
Body weight
Body weight in pounds.
Time frame: Day 1, 21, 42, 56
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