Treatment of skin issues caused by cancer medications

A Randomized, Placebo-controlled, Parallel Phase 2a Dose-ranging Study to Investigate the Efficacy, Safety, and Tolerability of Topical HT-001 for the Treatment of Skin Toxicities Associated With Epidermal Growth Factor Receptor Inhibitors

This study is testing a new gel to see if it can help people with skin problems caused by cancer medications feel better.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 152 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Hoth Therapeutics, Inc. (Academic / other)
• Drugs / interventions: cetuximab, panitumumab, necitumumab, pertuzumab, amivantamab, gefitinib, erlotinib, osimertinib, lapatinib, afatinib, dacomitinib, neratinib, lazertinib, chemotherapy, radiation
• Locations: 12 sites (Irvine, California and 11 other locations)
• Trial ID: NCT05639933 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the efficacy, safety, and tolerability of HT-001 Topical Gel for treating skin toxicities, specifically acneiform rash, associated with Epidermal Growth Factor Receptor Inhibitors (EGFRIs). The study consists of two parts: an open-label phase to assess pharmacokinetics followed by a randomized, double-blind, placebo-controlled phase comparing different doses of HT-001 against a placebo. Participants will apply the gel daily for six weeks, and various assessment tools will be used to evaluate the severity of skin reactions and their impact on quality of life.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older who are receiving EGFRI therapy and have developed mild to moderate skin rashes.

Not a fit: Patients with severe skin reactions or those not receiving EGFRI therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly alleviate skin toxicities for patients undergoing EGFRI therapy, improving their quality of life.

How similar studies have performed: Other studies have shown promise in treating EGFRI-induced skin toxicities, but this specific approach with HT-001 is novel.

Eligibility criteria

Inclusion Criteria

1. Adult participant (ie, ≥ 18 years of age at Screening/Baseline \[V1\]) prescribed an approved EGFRI to treat cancer (indication within the approved labeling for the EGFRI and/or on National Comprehensive Cancer Network guidelines or equivalent local standards).

   1. Approved EGFRIs include, but are not limited to: gefitinib, erlotinib, osimertinib, lapatinib, afatinib, dacomitinib, neratinib, vandetanib, lazertinib, cetuximab, panitumumab, necitumumab, pertuzumab, and amivantamab-vmjw.
   2. Administration of an EGFRI, in combination with other drugs, for treatment of cancer is acceptable as long as the other drug is identified in the approved label of the EGFRI (eg, erlotinib with gemcitabine) or part of the NCCN guidelines or equivalent local standards.
2. Participant has developed a rash or symptoms of a rash (papular and/or pustular eruptions or cutaneous burning), as assessed by both Common Terminology Criteria for Adverse Events (CTCAE) grading and ARIGA scales (severity ≤ 3) with overall involvement ≤ 30% BSA.
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
4. Predicted life expectancy ≥ 3 months.
5. Participant is able and willing to comply with contraceptive requirements
6. Participant must have the ability and willingness to attend the necessary visits (telehealth and in person).
7. Participant must be willing and able to provide written informed consent after the nature of the study has been explained and prior to the commencement of any study procedures.

Exclusion Criteria

1. Participant has severe cutaneous toxicity (severity = 4 on the CTCAE grading and ARIGA scales) or cutaneous toxicity involvement that is \> 30% BSA, or other severe systemic toxicity (severity \> 3 on the CTCAE v5.0 scale) as a result of EGFRI therapy.
2. Participant has any underlying physical or psychological medical condition that, in the opinion of the Investigator, would make it unlikely that the participant would comply with the protocol or complete the study per protocol.
3. Participant 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 participant.
4. Participant has abnormal laboratory values at Screening/Baseline (V1):

   1. Absolute neutrophil count \< 1000/mm3 and WBC count \< 3000/mm3
   2. Platelet count \< 50,000/mm3
   3. Aspartate transaminase (AST) \> 2.5 × upper limit of normal (ULN)
   4. Alanine transaminase (ALT) \> 2.5 × ULN
   5. Bilirubin \> 1.5 × ULN
   6. Creatinine \> 1.5 × ULN
5. Participant has a known history of QT interval prolongation.
6. Participant has a prescribed cancer treatment plan that requires radiation treatment to the head, neck, or upper trunk concurrent with EGFRI therapy or has previously received radiation therapy within 4 weeks prior to Screening/Baseline (V1).
7. Participant has received aprepitant or other neurokinin-1 receptor antagonist within 4 weeks prior to Screening/Baseline (V1).
8. Participant has had prior treatment with an investigational drug within 4 weeks prior to Screening/Baseline (V1), or at least 8 half-lives of the drug, whichever is longer.
9. Participant has an active infection (eg, pneumonia or pneumonitis) or any uncontrolled disease except for the malignancy that, in the opinion of the Investigator, might confound the result or the study or pose unwarranted risk in administering the study drug to the participant.
10. Participant has received non-stable escalating doses of topical antibiotics, topical steroids, or other topical treatments within 14 days prior to Screening/Baseline (V1). Participants who have been on stable doses of topical antibiotics, topical steroids, or other topical treatments for 14 days or more are allowed to be enrolled and to stay on their current prescription. Reduction in dose due to improvement in EGFRI-related toxicities is allowed.
11. Participant has used non-stable escalating doses of systemic steroids within 14 days prior to Screening/Baseline (V1) excluding low dose systemic corticosteroids as part of standard of care for prevention or treatment of chemotherapy-induced nausea and vomiting; acceptability of the steroid and dose is to be determined by the Investigator. Participants who have been on a stable dose of systemic steroids for 14 days or more are allowed to be enrolled and to stay on their current prescription. Reduction in dose due to improvement in EGFRI related toxicities is allowed. Use of steroid inhalers and nasal corticosteroids is allowed.
12. Participant has received non-stable escalating dose treatment with a systemic antibiotic within 14 days prior to Screening/Baseline (V1). Participants who have been on stable doses of systemic antibiotics for 14 days or more are allowed to be enrolled and to stay on their current prescription. Reduction in dose due to improvement in EGFRI-related toxicities is allowed.
13. Participant has received concomitant treatment with pimozide, moderate to strong cytochrome p450 (CYP) 3A4 inhibitors (diltiazem, ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, nelfinavir), or strong CYP3A4 inducers (rifampin, carbamazepine, phenytoin) within 30 days of Screening/Baseline (V1).
14. Participant has a history of hypersensitivity to aprepitant or any component of HT-001.
15. Participant is pregnant or lactating at Screening/Baseline (V1) or planning to become pregnant (self or partner) at any time during the study, including the follow-up period.

Where this trial is running

Irvine, California and 11 other locations

• UCI Health - CIACC — Irvine, California, United States (Recruiting)
• UC Irvine - Chao Family Cancer Center — Orange, California, United States (Recruiting)
• Regis Clinical Research — Miami, Florida, United States (Recruiting)
• Dana Farber Cancer Institute — Boston, Massachusetts, United States (Recruiting)
• NYU Langone Health — Mineola, New York, United States (Recruiting)
• Northwell Physician Partners Dermatology — New Hyde Park, New York, United States (Recruiting)
• Montefiore Medical Center — The Bronx, New York, United States (Recruiting)
• Gabrail Cancer & Research Center — Canton, Ohio, United States (Recruiting)
• MD Anderson Cancer Center — Houston, Texas, United States (Recruiting)
• Centrum Medyczne Pratia Krakow — Krakow, Poland (Active_not_recruiting)
• NZOZ Neuromed M. i M. Nastaj Sp.P — Lublin, Poland (Active_not_recruiting)
• Hospital Sant Joan de Deu-Fundacio Althaia — Manresa, Spain (Active_not_recruiting)

Study contacts

• Study coordinator: Hayley Springer

Conditions Acneiform Eruption Due to Chemical; Xerosis Cutis; Paronychia; Acneiform rash; EGFR inhibitor; Cutaneous toxicities