Overview
This study is a multicenter, open-label, Phase I single-arm clinical trial evaluating the safety and tolerability of a topical AKK probiotic preparation (Akkermansia muciniphila) for the prevention and treatment of radiation-induced skin injury in patients receiving radiotherapy for breast cancer, head and neck cancer (including nasopharyngeal carcinoma). A total of 40 participants are planned to receive the AKK preparation applied to the radiation field three times daily, starting one day before the first radiotherapy fraction and continuing until 14 days after the last fraction. The primary outcome is the incidence of grade ≥2 acute radiation dermatitis (ARD) assessed by RTOG and CTCAE criteria. Secondary outcomes include changes in skin micro-features under digital dermoscopy, skin microbiota composition, quality of life (Skindex-16), and safety.
Description
Background and Rationale Radiation-induced skin injury (RISI) affects approximately 95% of radiotherapy patients in China, with 85% experiencing moderate to severe acute radiation dermatitis (ARD). Current topical treatments have limited efficacy. Akkermansia muciniphila (AKK), a commensal gut bacterium, exhibits anti-inflammatory and barrier-repairing properties via NF-κB, Nrf2, and NLRP3 pathways. This is the first study to apply inactivated AKK topically for RISI.
Detailed Intervention The investigational product is an inactivated whole-cell AKK preparation (provided by State Key Laboratory of Biotherapy, Sichuan University). Participants apply 140 µL per 25 cm² of radiation field (delivering 7 × 10⁷ CFU) three times daily: once 1 hour before each radiotherapy fraction, and twice at other times (e.g., afternoon and bedtime). Treatment begins one day before the first fraction (after baseline skin sampling) and continues until 14 days after the last fraction.
Study Procedures After written informed consent, screening (D-28 to D-1) includes history, physical exam, and ECOG performance status. At baseline (D-1): skin microbiome sampling, digital dermoscopy, RTOG/CTCAE grading, and Skindex-16. During radiotherapy, weekly visits (on the first fraction day of each week, before that fraction) repeat all assessments. Treatment phase duration varies by fraction number (15, 25, 30, or 33 fractions). Follow-up visits occur at days 14, 30, 60, and 90 after the last fraction, with the same assessments. Adverse events are monitored throughout and graded by CTCAE v6.0.
Sample Size Justification Assuming historical incidence of grade ≥2 ARD = 50%, expected incidence with AKK = 30% (one-sided α=0.05, power=80%), the required sample size is 37. Accounting for 8% dropout, final N = 40.
Statistical Analysis Primary analysis uses intention-to-treat population. Incidence of grade ≥2 ARD will be compared to historical control using a one-sample proportion test. Secondary endpoints (skin microbiome, dermoscopy features, Skindex-16, adverse events) will be summarized descriptively with 95% confidence intervals. Continuous variables will be compared using paired t-tests or Wilcoxon signed-rank tests as appropriate.
Data Monitoring A Data Safety Monitoring Committee (DSMC) composed of oncologists, pharmacologists, biostatisticians, and GCP experts will review safety and efficacy data every 6 months and may recommend early termination or protocol modification based on predefined stopping rules (e.g., grade 4 AEs in \>10% of participants).
Ethical Approval The protocol (version 2.0, 4 February 2026) and informed consent form (version 2.0, 4 February 2026) were approved by the Medical Ethics Committee of Jintang County First People's Hospital (approval No. 20260302002, dated 2 March 2026). Any amendments will be submitted for ethical review before implementation.
Eligibility
Inclusion Criteria:
- Diagnosis of breast cancer, head and neck cancer (including nasopharyngeal carcinoma) receiving radiotherapy
- Age ≥18 years and ≤75 years, any sex
- Signed written informed consent
- Radiation field skin area can be localized and skin inflammation can be assessed
- ECOG performance status 0-1, life expectancy ≥3 months
- Adequate major organ function
- Fertile patients (both sexes) must use effective medical contraception during the study and for 6 months after the last dose
- Willing to comply with follow-up and skin image collection
Exclusion Criteria:
- Cognitive impairment preventing understanding of the study
- Use of antibiotics or antifungals within 1 month
- Previous treatment with other bacterial preparations
- Participation in other bacterial therapy trials
- Any abnormality (e.g., scar, tattoo) in the radiation field that would interfere with assessment
- Allergy to probiotics or any component of the study preparation; history of severe allergic reactions (e.g., anaphylaxis, angioedema, respiratory distress, allergic purpura, Arthus reaction)
- Use of immunosuppressive drugs
- Symptomatic or rapidly progressive central nervous system metastases, extensive lung metastases causing dyspnea, tumor invading major vessels or nerves
- Poorly controlled cardiac disease (NYHA class ≥2 heart failure, unstable angina, myocardial infarction within 1 year, clinically significant arrhythmia requiring treatment)
- Pregnancy or breastfeeding
- Active tuberculosis, bacterial or fungal infection (grade ≥2 per CTCAE), or HIV infection
- Substance abuse or psychiatric disorder
- Active autoimmune disease or history thereof (exceptions: vitiligo, childhood asthma fully resolved with no intervention in adulthood)
- History of alcohol or drug abuse
- Planned pregnancy from screening until 12 months after last treatment
- Any concomitant condition that, in the investigator's judgment, would compromise patient safety or study completion
- Any other condition deemed unsuitable for enrollment by the investigator
- Inability to provide written informed consent
