Topical Dermaprazole for Radiation Dermatitis in Breast Cancer and Head and Neck Cancer Patients (TOPAZ)

Study Overview
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Brief Summary
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Radiotherapy is a mainstay of treatment in head and neck cancer and breast cancer treatment, typically following surgery and/or chemotherapy. Radiation dermatitis, which involves redness, dryness, and/or peeling of the skin, occurs in up to 95% of patients receiving radiation therapy. There is currently no standard therapy for this treatment-related adverse effect. The aim of this study is to investigate the safety and tolerability (Phase I) and preliminary efficacy (Phase II) of prophylactic esomeprazole cream ( termed Dermaprazole) in patients who require radiation for either breast cancer in the postmastectomy setting or head and neck cancer in the definitive or adjuvant setting.

Detailed Description
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For this study, patients will be stratified into one of the following two arms: 1) head and neck or 2) breast cancer. All study participants will begin using Dermaprazole for 1-2 weeks prior to receiving radiation. During the CT Simulation, study participants will be instructed to apply Dermaprazole in a patch test area - an area of the chest outside of the field of radiation. This is to assess for immediate skin reactions including itching, irritation and allergy. If there are no immediate allergic reactions at the conclusion of the simulation visit, the study participant will be instructed to apply the cream in the area that will be irradiated in addition to the patch test area for 1-2 weeks until the radiation starts. During this period, if the patient is found to have no adverse events, they will then continue daily application both in the patch test area and in the radiation field during radiotherapy, and for 2 weeks after they complete their radiation treatment. During the entire time while using the Dermaprazole, study participants will be evaluated for adverse events such as contact dermatitis in the patch test area as well as radiation dermatitis within the treatment field. All participants will be followed for 6 months after the final Dermaprazole application. Two dose levels of Dermaprazole (1% and 2%) will be evaluated in the combination Phase I/II dose escalation/de-escalation BOIN design study evaluating preliminary efficacy at the Maximum Feasible Dose (MFD). The Dermaprazole will be initiated at a dose of 1% and escalated to 2% as appropriate based on the number of adverse events. A Dose Limiting Toxicity (DLT) will be defined as any of the following: a) any > Grade 2 skin toxicity outside the radiation field (Macules/ papules covering 10-30% of the area with or without symptoms of pruritus, burning, tightness), b) any > Grade 2 radiation dermatitis (Moderate to brisk erythema; patchy moist desquamation, mostly confined to skin folds and creases; moderate edema) inside the radiation field that is probably or definitely related to Dermaprazole (AE attribution will be at the discretion of the study PI/Co-I). c) Any > Grade 4 radiation dermatitis inside the radiation field. A DLT will be detected from the first day the subject starts applying the Dermaprazole cream until 1 month after the subject has completed their last radiation treatment. Dermatitis will be evaluated by a radiation oncologist on a weekly basis using the Common Terminology Criteria for Adverse Events (CTCAE) V5.0 criteria, and all radiation dermatitis scores will be independently verified by a dermatologist who will evaluate the photographs at the end of treatment. Patient reported quality of life will be evaluated using a validated survey instrument called SkinDex16.

Official Title
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A Phase I/II Study of Dermaprazole For Radiation Dermatitis in Post-Mastectomy Breast Cancer and Head and Neck Cancer Patients.

Conditions
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Breast Cancer, Radiation Dermatitis, Head and Neck Cancer

Intervention / Treatment
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* Drug: Dermaprazole 1%
* Drug: Dermaprazole 2%


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Arm B: Breast cancer arm Women with breast cancer, treated with ipsilateral i) Simple (total) mastectomy (nipple sparing mastectomy is same as total mastectomy), OR ii) Modified radical mastectomy, OR iii)Radical mastectomy Histological diagnosis of invasive ductal or lobular carcinoma (diagnosed within 2 years of enrollment) Planned to receive adjuvant chest wall radiation of at least 40Gy or higher biologically equivalent dose (BED) Age 18 years or older Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2 Written Informed Consent History and Physical within 12 weeks of enrollment Arm A: Head & Neck cancer arm Patients with squamous cell carcinoma of the head and neck confirmed with institutional pathology (diagnosed within 2 years of enrollment) Planned to receive concurrent chemoradiation with any radiosensitizing regimen (such as cisplatin) of at least 60 Gy or higher (note: chemotherapy per medical oncology and otolaryngology). Age 18 years or older ECOG performance status 0 to 2 Written Informed Consent History and Physical within 12 weeks of enrollment Exclusion Criteria: Arm B: Breast Cancer arm Prior chest wall radiotherapy Any serious medical condition or illness that would preclude the safe administration of the study drug including, but not limited to: active infection, symptomatic heart failure, unstable angina, psychiatric illness or social situations that would limit compliance with treatment Concurrent chemotherapy Biopsy-proven epidermal involvement or positive margins Open wound at time of consultation, or delayed surgical wound healing as defined as open wound >8 weeks post-op Known active collagen vascular disease such as systemic lupus erythematous, scleroderma or dermatomyositis. Allergy or sensitivity to proton pump inhibitors Pregnancy or breast feeding Use of clopidrogrel, St. Johns Wort, rifampin, or methotrexate Arm A: Head & Neck cancer arm Prior head and neck radiotherapy Any serious medical condition or illness that would preclude the safe administration of the study drug including, but not limited to, active infection, symptomatic heart failure, unstable angina, psychiatric illness or social situations that would limit compliance with treatment Lack of concurrent chemotherapy Open wound at time of simulation Known active collagen vascular diseases such as systemic lupus erythematous, scleroderma or dermatomyositis. Allergy or sensitivity to proton pump inhibitors Pregnancy or breast feeding (pregnancy test prior to CT simulation if the patient is not on a medication that prevents pregnancy) Use of clopidrogrel, St. Johns Wort, rifampin, or methotrexate

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dermaprazole 1% (Arm A:Head and neck)<br>Dermaprazole cream at a concentration of 1% will be applied to the skin twice daily starting from CT simulation throughout the radiation treatment period. | Drug: Dermaprazole 1%<br>* Dermaprazole cream at a concentration of 1% will be applied to the irradiated area twice daily for up to 7 weeks<br>|
| Experimental: Dermaprazole 1% (ArmB: Breast)<br>Dermaprazole cream at a concentration of 1% will be applied to the skin twice daily starting from CT simulation throughout the radiation treatment period. | Drug: Dermaprazole 1%<br>* Dermaprazole cream at a concentration of 1% will be applied to the irradiated area twice daily for up to 7 weeks<br>|
| Experimental: Dermaprazole 2% (Arm A: Head and neck)<br>Dermaprazole cream at a concentration of 2% will be applied to the skin twice daily starting from CT simulation throughout the radiation treatment period. | Drug: Dermaprazole 2%<br>* Dermaprazole cream at a concentration of 2% will be applied to the irradiated area twice daily for up to 7 weeks<br>|
| Experimental: Dermaprazole 2% (Arm B: Breast)<br>Dermaprazole cream at a concentration of 2% will be applied to the skin twice daily starting from CT simulation throughout the radiation treatment period. | Drug: Dermaprazole 2%<br>* Dermaprazole cream at a concentration of 2% will be applied to the irradiated area twice daily for up to 7 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with Dose-Limiting Toxicity(DLT) in phase I | A DLT is defined as any of the following:1) Any > Grade 2 skin toxicity outside the radiation field for patients in both the H&N and BC groups;2). Any > Grade 2 radiation dermatitis inside the radiation field that is probably or definitely related to Dermaprazole for patients in both the H&N and BC groups. (AE Attribution will be at the discretion of the study PI/Co-I);3) 3. Any Grade > 4 radiation dermatitis inside the radiation field for any patients in both the H&N and BC groups. Any skin reaction ≥Grade 2 will lead to immediate halting of Dermaprazole use in that patient and reported as an adverse event and a dose limiting toxicity. | from the first day applying the Dermaprazole cream until 1 month after the subject has completed their last radiation treatment | 
| Rate of clinically bothersome radiation dermatitis at maximum feasible dose in phase II | The rate of radiation dermatitis is defined as the number of participants with radiation dermatitis divided by the total number of participants in each arm. Radiation dermatitis will be determined by the radiation oncologist and defined using NCI Common Terminology Criteria for Adverse Events (CTCAE version 5) for dermatitis radiation. In particular, the individual components of radiation dermatitis will be recorded: erythema, desquamation, edema, bleeding, skin necrosis and skin ulceration. This evaluation will be conducted in Arm A (head and neck) and Arm B (breast) separately. | at weekly during radiation treatment, up to 7 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of grade 2 or higher acute radiation dermatitis | The proportion of patients with maximum observed acute grade 2, 3, and 4 skin reactions will be expressed in percentage. In particular, the individual components of radiation dermatitis will be recorded: erythema, desquamation, edema, bleeding, skin necrosis and skin ulceration. | from the first day the subject applies the cream to the end of the 6 month follow up period | 
| Median- occurrence time of grade 2 or higher acute radiation dermatitis | Median-occurrence of grade 2 or higher acute radiation dermatitis time on the Kaplan-Meier method is defined as the time between the first time of applying the cream and the time of occurrence of grade 2 or higher acute radiation dermatitis. | from the first day the subject applies the cream to the end of the 6 month follow up period | 
| Median-healing time of grade 2 or higher acute radiation dermatitis develops | Median-healing time of grade 2 or higher acute radiation dermatitis developing time on the Kaplan-Meier method is defined from time to develop the grade 2 or higher acute radiation dermatitis after applying the cream to healing the event. | from the first day the subject applies the cream to the end of the 6 month follow up period | 
| Median of the peak score of each QOL component | Patient reported quality of life will be evaluated using a validated survey instrument called SkinDex16 questionnaire for QOL. The Skindex-16 assessment tool is designed to capture patient-reported assessments of subjective adverse effects. It consists of a short 16-item assessment completed by the patient, with each item rated on a 7-point Likert scale (0=never bothered to 6=always bothered). | at before and after Dermaprazole cream application at the CT simulation visit, weekly during radiation treatment up to 7 weeks, 1 and 6 month follow-up after completion of all radiation therapy | 
| Number of missed treatments due to skin toxicity | The missing numbers of treatment due to skin toxicity will be counted. | at weekly during radiation treatment, up to 7 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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radiation therapy, breast cancer, Radiation dermatitis, post-mastectomy, head and neck cancer