Overview
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.
Description
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.
Eligibility
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