A Phase I/II Study of Dermaprazole For Radiation Dermatitis in Post-Mastectomy Breast Cancer Patients.
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 3
- 试验地点
- 2
- 主要终点
- Number of Participants With Dose-Limiting Toxicity(DLT) in Phase I
研究概览
简要总结
Radiotherapy is a mainstay of treatment in breast cancer treatment, in the adjuvant setting. Radiation dermatitis occurs in up to 65% of these patients; currently, there is no standard of care for this treatment-related toxicity. 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 breast cancer in the adjuvant setting.
详细描述
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 patch test for 2-4 days to assess for contact dermatitis and if no itching or rash at that time (evaluation will be conducted via phone call). Patients will be questioned regarding any visible skin changes or irritation (itching, peeling, scaling), and patients responding in the affirmative will be asked to present for clinic visit or send photographs for visual classification according to the scale outlines in Table 1 below. Skin reactions matching a score of 3 will be evaluated with a second clinic visit between 2 to 7 days after initial application. Any skin reactions of score 4 or 5 at final assessment will be deemed to be positive for allergic contact dermatitis, and patients will be deemed positive for allergic contact dermatitis.
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, within the radiation field that is probably or definitely related to Dermaprazole. Dermatitis will be evaluated by a radiation oncologist on a weekly basis using the Common Terminology Criteria for Adverse Events (CTCAE) V5.0 criteria. Patient reported quality of life will be evaluated using a validated survey instrument called SkinDex16.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Supportive Care
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Women with breast cancer, treated with ipsilateral i) Simple (total) mastectomy, OR ii) Modified radical mastectomy, OR iii)Radical mastectomy, OR iv) Segmental mastectomy, OR v) Skin sparing/nipple sparing 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
- •Women of childbearing potential (any woman with menses in the last 12 months) must agree to pregnancy testing and contraceptive use throughout the study period. Testing consists of human chorionic gonadotropin (HCG) urine testing, which if suspected to be falsely positive may be confirmed by ultrasound. If ultrasound is negative, patient is considered not pregnant and eligible for inclusion in the study. In addition to routine contraception method such as barrier devices, hormonal methods, and intrauterine devices, heterosexual celibacy, and surgical sterility (hysterectomy, bilateral oophorectomy, bilateral tubal ligation, or a partner with history of vasectomy) is considered acceptable. If a celibate patient chooses to become sexually active during the study period, she must use one of the listed methods of contraception throughout the study period.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
- •Written Informed Consent
- •History and Physical within 12 weeks of enrollment
排除标准
- •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
研究组 & 干预措施
Dermaprazole 1% (Breast)
Dermaprazole cream at a concentration of 1% will be applied to the skin twice daily starting from CT simulation throughout the radiation treatment period.
干预措施: Dermaprazole 1% (Drug)
Dermaprazole 2% (Breast)
Dermaprazole cream at a concentration of 2% will be applied to the skin twice daily starting from CT simulation throughout the radiation treatment period.
干预措施: Dermaprazole 2% (Drug)
结局指标
主要结局
Number of Participants With Dose-Limiting Toxicity(DLT) in Phase I
时间窗: from the first day applying the Dermaprazole cream until 1 month after the subject has completed their last radiation treatment, up to 13 weeks
A DLT is defined as any of the following:1) 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); 2). Any \> Grade 2 radiation dermatitis (Moderate to brisk erythema; patchy moist desquamation, mostly confined to skin folds and creases; moderate edema) within the treatment field that is probably or definitely related to Dermaprazole. Dermatitis will be evaluated by a radiation oncologist on a weekly basis using the Common Terminology Criteria for Adverse Events (CTCAE) V5.0 criteria. Patient reported quality of life will be evaluated using a validated survey instrument called SkinDex16.
Rate of Clinically Bothersome Radiation Dermatitis at Maximum Feasible Dose in Phase II
时间窗: at weekly during radiation treatment, up to 7 weeks
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.
次要结局
- Number of Missed Radiation Treatments Due to Skin Toxicity(at weekly during radiation treatment, up to 7 weeks)
- Number of Participants With 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- Occurrence Time 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(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 Total QOL Score(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)
研究者
Daniel Hamstra
Chairman/Professor
Baylor College of Medicine