HT-001 for Skin Side Effects from Cancer Therapy

(CLEER Trial)

Recruiting at 9 trial locations

Overseen By Hayley Springer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Hoth Therapeutics, Inc.

Must be taking: EGFR inhibitors

Must not be taking: Neurokinin-1 antagonists, CYP3A4 inhibitors

Disqualifiers: Severe toxicity, Skin disorders, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

152 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not require you to stop taking your current medications if they are stable. If you are on stable doses of topical or systemic antibiotics, steroids, or other treatments for 14 days or more, you can continue them. However, certain medications like pimozide, some antibiotics, and specific enzyme inhibitors or inducers should not be taken within 30 days before starting the trial.

How is the drug HT-001 different from other treatments for skin side effects from cancer therapy?

HT-001 is a topical gel specifically designed to address skin side effects from cancer therapy, which may offer a more targeted approach compared to systemic treatments. Unlike some treatments that can enhance radiation side effects, HT-001 aims to alleviate them, potentially providing a novel option for patients experiencing skin toxicity. ^{1 2 3 4 5}

Research Team

Mario Lacouture, MD

Principal Investigator

NYU Langone Health

Eligibility Criteria

This trial is for adults over 18 with cancer, who are starting EGFRI treatment within 4 weeks and have developed a rash or symptoms of it. They must be able to consent, attend visits, expect to live at least 3 months, follow contraceptive rules, and have an ECOG status of 0-2. Excluded are those with less than 8-week EGFRI therapy plan, recent radiation to head/neck/trunk, active infections or uncontrolled diseases that could affect the study's outcome.

Inclusion Criteria

I can and will attend all required visits, both in person and via telehealth.

I am an adult prescribed an EGFRI for my cancer treatment.

Predicted life expectancy ≥ 3 months

Exclusion Criteria

Patient has a history of other skin disorders (eg, atopic dermatitis, psoriasis, recurrent skin infections) or history of illness that, in the opinion of the Investigator, would confound results of the study or pose unwarranted risk in administering study drug to the patient

Patient has a history of hypersensitivity to aprepitant or any component of HT-001

Patient has abnormal laboratory values at Screening/Baseline (V1): Absolute neutrophil count < 1000/mm3 and WBC count < 3000/mm3, Platelet count < 50,000/mm3, AST > 2.5 × ULN, ALT > 2.5 × ULN, Bilirubin > 1.5 × ULN, Creatinine > 1.5 × ULN

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Open-label Treatment

Participants receive HT-001 2% Gel to measure pharmacokinetics

6 weeks

Daily application

Randomized Treatment

Participants are randomized to receive one of three concentrations of HT-001 or placebo

6 weeks

Daily application

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

1 visit (in-person)

Treatment Details

Interventions

• HT-001
• HT-001 Placebo

Trial Overview The trial tests HT-001 Topical Gel in various concentrations (0.5%, 1%, and 2%) against a placebo for treating skin toxicities caused by EGFR inhibitors in cancer patients. It has two phases: an open-label phase where all receive HT-001 and a blinded phase where participants get either the gel or placebo randomly.

Participant Groups

Group I: Open-Label PK Cohort Experimental Treatment 1 Intervention

Topical treatment with HT-001 2% Gel unblinded.

Group II: Randomized, Double Blind Cohort Placebo Group 4 Interventions

Topical treatment with HT-001 (2%, 1%, or 0.5%) or placebo (HT-001 vehicle), blinded

Who Is Running the Clinical Trial?

Hoth Therapeutics, Inc.

Lead Sponsor

Trials

2

Recruited

180+

Worldwide Clinical Trials

Collaborator

Trials

70

Recruited

15,800+

Findings from Research

The study developed a novel nanoemulgel formulation of chrysin, a flavonoid with anti-cancer properties, which significantly enhances the delivery and absorption of the drug through the skin, showing a mean droplet size of 156.9 nm and improved percutaneous absorption in ex vivo tests.

In vitro tests demonstrated that this formulation effectively reduced the required dose to achieve therapeutic effects on melanoma cell lines, while biocompatibility testing confirmed its safety for use, indicating it could be a promising treatment for localized skin cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical Nanoemulgel for the Treatment of Skin Cancer: Proof-of-Technology. Nagaraja, S., Basavarajappa, GM., Attimarad, M., et al.[2021]

A case of radiation recall dermatitis (RRD) occurred in a 65-year-old man one year after receiving radiotherapy for head and neck cancer, linked to the use of hypericin (St. John's wort) during and after treatment.

The patient's skin reactions intensified during radiotherapy and recurred months later, highlighting the potential for certain drugs, like hypericin, to increase skin toxicity from radiotherapy, which emphasizes the need for healthcare providers to inquire about all medications, including alternative therapies, that patients may be taking.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhanced radiation sensitivity and radiation recall dermatitis (RRD) after hypericin therapy -- case report and review of literature. Putnik, K., Stadler, P., Schäfer, C., et al.[2021]

Acute skin toxicity affects 70%-100% of breast cancer patients undergoing radiation therapy, but the impact on their daily lives is complex and goes beyond just visible skin changes.

Interviews with seven women revealed that their experiences of skin reactions are intertwined with psychological aspects and the need for better information and support, highlighting the importance of a holistic approach to patient care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Women's experience of acute skin toxicity following radiation therapy in breast cancer. Andersen, ER., Eilertsen, G., Myklebust, AM., et al.[2022]

Nanogel creams containing paclitaxel (PTX) and temozolomide (TMZ) were developed for topical melanoma treatment, showing improved drug penetration through rodent skin compared to traditional formulations.

In vitro studies demonstrated that the combination of PTX and TMZ was synergistically effective against melanoma cells, and preliminary in vivo results indicated a trend towards reduced tumor volume in mice treated with the nanogel creams.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical Cream Carrying Drug-Loaded Nanogels for Melanoma Treatment. Rahman, S., Haque, TN., Sugandhi, VV., et al.[2023]

In a clinical trial involving 30 breast cancer patients undergoing radiotherapy, a new hyaluronan (HA) formulation did not show significant differences in preventing skin toxicity compared to a placebo, as evaluated by physicians at week 5 during treatment and week 2 post-treatment.

While some patients preferred the HA formulation for skin appearance, this preference was not statistically significant, indicating that the HA cream may not provide substantial radioprotective benefits overall, except potentially for patients with larger breasts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel hyaluronan formulation for preventing acute skin reactions in breast during radiotherapy: a randomized clinical trial. Rahimi, A., Mohamad, O., Albuquerque, K., et al.[2020]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Topical Nanoemulgel for the Treatment of Skin Cancer: Proof-of-Technology. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Enhanced radiation sensitivity and radiation recall dermatitis (RRD) after hypericin therapy -- case report and review of literature. [2021]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Women's experience of acute skin toxicity following radiation therapy in breast cancer. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Topical Cream Carrying Drug-Loaded Nanogels for Melanoma Treatment. [2023]

5. Germany pubmed.ncbi.nlm.nih.gov

Novel hyaluronan formulation for preventing acute skin reactions in breast during radiotherapy: a randomized clinical trial. [2020]