Exploring Gut Microbiome Differences in Female Cancer Patients With Varied Ovarian Function and Fertility Outcomes Following Immune Checkpoint Inhibitor Therapy

Prior treatment

• Concurrent use of other tumor treatment modalities during the study, including but not limited to: chemotherapy, radiotherapy, immunotherapy, microbial therapy, traditional Chinese medicine, and other investigational therapies;
• Patients with prior radiotherapy or chemotherapy causing irreversible damage to ovarian function;
• Patients with known non-response to immunomodulatory therapy;
• Patients with unexplained menstrual irregularities or long-term hormone medication use;
• Patients who underwent major surgery within 3 weeks prior to study initiation or have not yet recovered from surgery;
• Clinically unresolved prior treatment toxicity (≥ Grade 2, excluding alopecia, neuropathy, lymphopenia, or skin hypopigmentation);

Other illness

• History of bilateral ovarian-related surgery;
• Individuals with known allergy to ICIs or their components;
• Patients with chronic gastrointestinal disease or known dysbiosis (e.g., Crohn's disease, ulcerative colitis);
• Subjects with other malignancies within the past 3 years;
• Patients with severe, uncontrolled medical conditions or those deemed by the investigator to be generally unsuitable for study participation, including but not limited to: active viral infections such as HIV, hepatitis B, hepatitis C; severe cardiovascular disease, uncontrolled ventricular arrhythmias, myocardial infarction within the past 3 months; uncontrolled grand mal seizures, unstable spinal cord compression, superior vena cava syndrome, or other psychiatric conditions affecting informed consent; uncontrolled hypertension despite medication; immunodeficiency (excluding splenectomy) or other conditions the investigator deems likely to expose the subject to high toxicity risk;

Lab values

• Receipt of platelet or red blood cell transfusion within 3 days prior to initiation of study drug treatment;

Other

• Individuals involved in the planning or implementation of the study;
• Patients who frequently consume fermented foods;
• Any history or current clinical evidence suggesting potential for confounding study results, compromising patient compliance throughout the study, or acting against the patient's best interests;
• Pregnant or lactating patients, or patients planning pregnancy during the study period.

• Collect serum hormone levels post-ICIs treatment to observe the impact of ICIs therapy on female patients.
• Informed consent must be obtained and documented at the research center prior to initiating any trial procedures.
• Female patients aged 18-38 years.
• Patients with histologically confirmed solid tumors or soft tissue sarcomas diagnosed via open surgery, laparoscopic surgery, or core needle biopsy.
• Patients scheduled to receive ICIs therapy or combination therapy including ICIs;
• Normal ovarian function and fertility prior to treatment, defined as regular menstrual cycles, normal serum FSH, LH, E2, P, and AMH levels, and normal gynecological ultrasound findings;
• No use of sex hormone medications within 6 months prior to enrollment, including but not limited to estrogens, anti-estrogens hormones, hormonal contraceptives, etc.;
• No use of antibiotics or probiotics within 3 months prior to enrollment;
• Availability of blood and stool specimens before and after treatment, with the subject's consent to provide these specimens to the central laboratory for study purposes, including but not limited to: i. Potential gut microbiota-related research. ii. Potential metabolite-related research;
• Expected survival \>12 weeks;
• ECOG performance status 0-2;
• Adequate organ function, including:
• Bone marrow function: Neutrophil count ≥1500/µL; Platelet count ≥100,000/ µL; Hemoglobin ≥10g/dL
• Liver function: Total bilirubin ≤1.5 times upper limit of normal (ULN) or direct bilirubin ≤1.0 times ULN; AST and ALT ≤2.5 times ULN, must be ≤5 times ULN if liver metastases present
• Renal function: Serum creatinine ≤1.5 times ULN, or creatinine clearance
  • 60 mL/min (calculated using Cockcroft-Gault formula) ;
• Understand the trial protocol and have the ability to comply with the trial plan throughout its duration, including cooperating with any required treatments, examinations, tests, follow-ups, and questionnaires;
• Patient is willing to cooperate with ICIs treatment and subsequent follow-up.