Resumen

El objetivo de este ensayo clínico es conocer el gel tópico HT-001 para el tratamiento de las toxicidades cutáneas inducidas por inhibidores del EGFR. Las principales preguntas que pretende responder son: * Determinar el efecto terapéutico de HT-001 para el tratamiento de pacientes que desarrollan erupción acneiforme sometidos a terapia con inhibidores del factor de crecimiento epidérmico (EGFRI) utilizando la escala de evaluación global del investigador de erupción acneiforme [ARIGA] * Evaluar la seguridad de HT-001 durante el tratamiento Los participantes aplicarán el gel HT-001 una vez al día durante 6 semanas, durante las cuales se evaluará el efecto en el tratamiento de la erupción acneiforme u otros trastornos cutáneos inducidos por la terapia con EGFRI utilizando diferentes herramientas de evaluación para medir la gravedad de la erupción, el dolor y el picor (prurito), así como el cambio en la calidad de vida. El estudio se completará en 2 períodos: el primer período es abierto (no ciego) y todos los pacientes recibirán el gel tópico HT-001 con el ingrediente activo; El segundo periodo es a ciegas y los pacientes serán asignados aleatoriamente para recibir una de las tres concentraciones de HT-001 o placebo. Los investigadores compararán HT-001 con el placebo en este segundo periodo para determinar si HT-001 proporciona un efecto terapéutico significativo.

Edad: 18 años o más

Género: Todos

Fecha de inicio: 07/19/2023

Fecha de finalización principal (estimada): 12/30/2026

Fecha estimada de finalización del estudio: 12/30/2026

Acepta voluntarios sanos: No

Propósito y descripción del ensayo

Este es un estudio de fase 2a multicéntrico, aleatorizado, doble ciego y controlado con placebo para determinar la dosis y evaluar la eficacia, seguridad y tolerabilidad de HT-001 para el tratamiento de la toxicidad cutánea inducida por EGFRI. El estudio incluirá pacientes adultos (≥ 18 años de edad) programados para recibir terapia con EGFRI inicial o repetida. El estudio se llevará a cabo en 2 períodos: Parte 1, una cohorte abierta de 12 pacientes para medir la farmacocinética del gel HT 001, seguida de la Parte 2, un estudio aleatorizado de grupos paralelos que compara 3 concentraciones de dosis de gel HT-001 con placebo (vehículo HT 001). Los pacientes en las cohortes aleatorizadas serán asignados aleatoriamente a 1 de los 4 grupos de tratamiento en una proporción de 2:2:2:1 (grupos activos = 2: placebo = 1). Todos los pacientes, tanto en el grupo de tratamiento abierto como en el grupo de tratamiento a ciegas, se aplicarán el fármaco en estudio una vez al día en cada zona afectada por toxicidad cutánea, hasta un 30 % de la superficie corporal afectada (SCA), incluyendo piel, cuero cabelludo y uñas. El objetivo del estudio es determinar la dosis mínima eficaz para su posterior investigación. Se evaluará el efecto de la dosis, junto con la seguridad en el lugar de aplicación y los efectos terapéuticos según los criterios de valoración primarios y secundarios.

Criterios de elegibilidad

Edad: 18 años o más

Género: Todos

Acepta voluntarios sanos: No

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. Estado funcional del Eastern Cooperative Oncology Group (ECOG) de 0 a 2.

4. Esperanza de vida prevista ≥ 3 meses.

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. Recuento absoluto de neutrófilos < 1000/mm3 y recuento de leucocitos < 3000/mm3

2. Recuento de plaquetas < 50.000/mm3

3. Aspartato transaminasa (AST) > 2,5 × límite superior de la normalidad (LSN)

4. Alanina transaminasa (ALT) \> 2,5 × LSN

5. Bilirrubina > 1,5 × LSN

6. Creatinina > 1,5 × LSN

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.