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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Other: DECLARAN cream

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.

• Study Type: Interventional
• Enrollment (Estimated): 25
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Simon Spazzapan, MD; Phone Number: +39 0434 659725; Email: spazzapan@cro.it

Study Locations

• Italy
  • Udine, Italy, 33100
    • Not yet recruiting
    • Azienda Sanitaria Universitaria del Friuli Centrale (ASUFC)
    • Contact: Elena Poletto, MD; Phone Number: +39 0432 552761; Email: elena.poletto@asufc.sanita.fvg.it
    • Principal Investigator: Elena Poletto, MD
  • Pordenone
    • Aviano, Pordenone, Italy, 33081
      • Recruiting
      • Centro di Riferimento Oncologico (CRO) di Aviano - IRCCS
      • Principal Investigator: Simon Spazzapan, MD
      • Contact: Simon Spazzapan, MD; Phone Number: +39 0434 659725; Email: spazzapan@cro.it
      • Principal Investigator: Camilla Lisanti

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DECLARAN cream; Patients will apply of DECLARAN cream is the investigational product based on NAC and urea	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the role of NAC plus urea-based cream (DECLARAN) in the prevention of Capecitabine-induced HFS in patient affected by breast cancer.	Cumulative incidence of any grade HFS (according CTCAE vs 5.0,)	up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate severe HFS	Cumulative incidence of grade 3 HFS according CTCAE vs 5.0	up to 2 years
To evaluate the impact of HFS on patients' quality of life at 6 weeks	Cumulative incidence of summary values of patient reported outcome (PRO) assessed with HFS-14 at 6 weeks	up to 2 years
To evaluate the impact of HFS on patients' quality of life at 12 weeks	Cumulative incidence of summary values of patient reported outcome (PRO) assessed with HFS-14 at 12 weeks	up to 2 years
To evaluate the impact of HFS on patients' quality of life at 24 weeks	Cumulative incidence of summary values of patient reported outcome (PRO) assessed with HFS-14 at 24 weeks	up to 2 years
To evaluate the safety of NAC plus urea-based cream	Frequecies of adverse events	up to 2 years

Collaborators and Investigators

• Sponsor: Centro di Riferimento Oncologico - Aviano
• Investigators: Principal Investigator: Simon Spazzapan, MD, Centro di Riferimento Oncologico di Aviano (CRO) - IRCCS; Principal Investigator: Camilla Lisanti, MD, Centro di Riferimento Oncologico di Aviano (CRO) - IRCCS

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2024
• Primary Completion (Estimated): May 15, 2026
• Study Completion (Estimated): May 15, 2026

Study Registration Dates

• First Submitted: October 10, 2024
• First Submitted That Met QC Criteria: October 10, 2024
• First Posted (Actual): October 15, 2024

Study Record Updates

• Last Update Posted (Actual): October 16, 2024
• Last Update Submitted That Met QC Criteria: October 14, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Dermatitis; Drug-Related Side Effects and Adverse Reactions; Drug Eruptions; Drug Hypersensitivity; Breast Neoplasms; Hand-Foot Syndrome
• Other Study ID Numbers: CRO-2023-28

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No