Effectiveness of an N-acetylcysteine and Urea-based Cream in Prevention of Capecitabine-induced HAND-foot Syndrome in Breast Cancer Patients

Official title

Phase II Trial to Determine the Effectiveness of an N-acetylcysteine and Urea-based Cream in Prevention of Capecitabine-induced HAND-foot Syndrome in Breast Cancer Patients

Overview

Breast cancer (BC) is the most frequent tumour in women. To date, among the available treatments, the use of Capecitabine, an oral prodrug of fluorouracil, has been shown activity in different setting. In advanced disease, Capecitabine is often used as monotherapy in patients pretreated with anthracycline, taxane or both. One of the most frequent toxicities reported by patients receiving capecitabine is hand-foot syndrome (HFS), with an incidence of grade 3 HFS of 28%. HFS, also known as palmar-plantar erythrodysesthesia syndrome, is initially characterized by palmoplantar numbness, tingling, or burning pain. These symptoms usually coincide with sharply demarcated erythema with or without edema, cracking, or desquamation. In advanced stages, blistering and ulceration may occur. Although HFS is not considered life threatening, it can be painful and interfere with daily activities, thusseriously compromising quality of life (QoL), therefore this toxicity is considered dose limiting.Moreover, consistent with the theory that Capecitabine and its metabolites induce an inflammatory effect, the use of COX-2 inhibitors is an emerging strategies, but more evidence are needed from largest study to confirm their efficacy. Similarly, N-acetylcysteine (NAC), an antioxidant, mucolytic and nephroprotective agent, that affects pathways involved in inflammatory conditions and that has demonstrated to be effective in several dermatologic conditions, could be useful in the management of Capecitabine-induced HFS. From this arises the present study that has the objective of evaluating the role of NAC plus urea-based cream in the prevention of Capecitabineinduced HFS in patient affected by breast cancer.

Detailed description

Breast cancer (BC) is the most frequent tumour in women. To date, among the available treatments, the use of Capecitabine, an oral prodrug of fluorouracil, has been shown activity in different setting. In advanced disease, Capecitabine is often used as monotherapy in patients pretreated with anthracycline, taxane or both.

One of the most frequent toxicities reported by patients receiving capecitabine is hand-foot syndrome (HFS), with an incidence of grade 3 HFS of 28%. HFS, also known as palmar-plantar erythrodysesthesia syndrome, is initially characterized by palmoplantar numbness, tingling, or burning pain. These symptoms usually coincide with sharply demarcated erythema with or without edema, cracking, or desquamation. In advanced stages, blistering and ulceration may occur. Although HFS is not considered life threatening, it can be painful and interfere with daily activities, thusseriously compromising quality of life (QoL), therefore this toxicity is considered dose limiting.Moreover, consistent with the theory that Capecitabine and its metabolites induce an inflammatory effect, the use of COX-2 inhibitors is an emerging strategies, but more evidence are needed from largest study to confirm their efficacy.

Similarly, N-acetylcysteine (NAC), an antioxidant, mucolytic and nephroprotective agent, that affects pathways involved in inflammatory conditions and that has demonstrated to be effective in several dermatologic conditions, could be useful in the management of Capecitabine-induced HFS.

From this arises the present study that has the objective of evaluating the role of NAC plus urea-based cream in the prevention of Capecitabineinduced HFS in patient affected by breast cancer.

Interventions

• Other DECLARAN cream
  Patients will apply 1 mL of DECLARAN cream, as a single pressure dispensing (1 for hands, 1 for feet), 2 times/day on hands and feet, starting 3 days before the beginning of treatment with capecitabine and for the first 24 consecutive weeks of treatment.

Primary outcome measures

• To evaluate the role of NAC plus urea-based cream (DECLARAN) in the prevention of Capecitabine-induced HFS in patient affected by breast cancer. [Time frame: up to 2 years]

Secondary outcome measures (5)

• To evaluate severe HFS [Time frame: up to 2 years]
• To evaluate the impact of HFS on patients' quality of life at 6 weeks [Time frame: up to 2 years]
• To evaluate the impact of HFS on patients' quality of life at 12 weeks [Time frame: up to 2 years]
• To evaluate the impact of HFS on patients' quality of life at 24 weeks [Time frame: up to 2 years]
• To evaluate the safety of NAC plus urea-based cream [Time frame: up to 2 years]

Eligibility criteria

Inclusion criteria

• Women and men ≥18 years old
• Patients with diagnosis of breast cancer with stage I-III radically operated with residual disease post neoadjuvant treatment or stage IV
• Patients candidated for capecitabine in a post-neoadjuvant or metastatic setting treated with 2000-2500 mg/m2 d1-14 q21, or 1500 mg daily continuously (metronomic schedule)
• Patients who provided written informed consent

Exclusion criteria

• Patients previously treated with drugs that may have induced HFS
• Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol
• Pregnant, lactating, or breastfeeding, or intending to become pregnant during the study or within 60 days after the final dose of study treatmen

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Prevention

Study locations

Italy · 2 centers

• Centro di Riferimento Oncologico (CRO) di Aviano - IRCCS — Aviano
• Azienda Sanitaria Universitaria del Friuli Centrale (ASUFC) — Udine

Identifiers

NCT: NCT06639178 · CRO-2023-28

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗