ctDNA-guided First-line Immuno-de-escalation Therapy for IVB-stage and Recurrent Cervical Cancer

Launched by OBSTETRICS & GYNECOLOGY HOSPITAL OF FUDAN UNIVERSITY · Mar 13, 2025

Keywords

ClinConnect Summary

This clinical trial is looking at a new way to treat women with advanced or recurrent cervical cancer using a method called immunochemotherapy, which helps the body’s immune system fight cancer. The unique part of this study is that it will use a blood test to check for circulating tumor DNA (ctDNA) to guide the treatment. This means that doctors will adjust the treatment based on how the cancer is responding, aiming to find the best length of therapy or when it might be safe to stop treatment.

To participate in the trial, women must be between 18 and 75 years old and have been diagnosed with stage IVB or recurrent cervical cancer, specifically certain types of cervical cancer like squamous cell carcinoma or adenocarcinoma. Participants will need to provide consent and must not have received other treatments for their cancer before joining the trial. Throughout the study, participants can expect regular check-ups and monitoring to ensure their health and the effectiveness of the treatment. It’s important to note that this trial is not yet recruiting participants, but it aims to gather accurate and reliable data to help improve treatment for cervical cancer in the future.

Gender

FEMALE

Eligibility criteria

• Inclusion Criteria:
• • Clinically diagnosed as stage IVB primary treatment and recurrent cervical cancer patients (this relapse has not been systematically treated); Histologically or cytologically confirmed recurrent or metastatic cervical cancer, pathological types are squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma; Age ≥18 years old and ≤75 years old, female; Signed written informed consent form, and able to comply with the visitation and related procedures specified in the protocol; Has not received systematic treatment for primary stage IVB or this relapse; Has at least one measurable lesion (RECIST 1.1 version); ECOG performance status 0-1; Estimated survival time ≥3 months; Menopausal trial participants must agree to use effective contraceptive measures during the trial; pregnant women must have a negative serum or urine pregnancy test.
• Good organ function:
• • Hematology (subjects will not be allowed to receive blood transfusion or growth factor support within 7 days of starting the study): i. Neutrophil count (ANC) ≥ 1.5 × 10\^9 /L (1,500/mm\^3); ii. Platelet count ≥ 100 × 10\^9 /L (100,000/mm\^3); iii. Hemoglobin ≥ 9.0 g/dL.
• Kidney:
• • i. Serum creatinine (SCr) ≤ 1.5 × ULN or creatinine clearance (CrCl) calculated value ≥ 50 mL/min \* using the Cockcroft-Gault formula to calculate CrCl; if cisplatin is planned to be used in combination, CrCl ≥ 60 mL/min;
• Liver:
• • i. Serum total bilirubin (TBil) ≤ 1.5 × ULN; for subjects with liver metastasis or with evidence of Gilbert's disease, TBil ≤ 3 × ULN; ii. AST and ALT ≤2.5 × ULN; for subjects with liver metastasis, AST and ALT ≤ 5 × ULN; iii. Serum albumin ≥ 28 g/L.
• Coagulation:
• • i. International normalized ratio and activated partial thromboplastin time ≤ 1.5 × ULN (unless the subject is undergoing anticoagulant treatment, and the coagulation parameters (PT/INR and aPTT) are within the expected range of anticoagulant treatment at screening) 11. Menopausal trial participants must agree to use effective contraceptive measures during the trial; pregnant women must have a negative serum or urine pregnancy test.
• Exclusion Criteria:
• • Patients with pathological types other than squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma (e.g., small cell carcinoma, clear cell carcinoma, etc.).
• • Patients with clinically significant hydronephrosis of the renal pelvis, judged by the investigator as not relievable by nephrostomy or ureteral stent placement. Presence of central nervous system metastasis or carcinomatous meningitis.
• • Patients with other active malignant tumors within 3 years prior to the first dose of medication, except for locally curable tumor types that are considered cured, such as cutaneous squamous cell carcinoma, cutaneous basal cell carcinoma, superficial bladder carcinoma, primary breast cancer.
• • Within 4 weeks prior to the first dose of medication, patients who have received the last cycle of concurrent radiochemotherapy aimed at radical or neoadjuvant/adjuvant purposes; within 2 weeks prior to the first dose of medication, patients who have received palliative radiotherapy (e.g., for bone metastasis); within 2 weeks prior to the first dose of medication, patients who have received drugs with immunomodulatory effects (e.g. thymic peptides, interferons, interleukin-2); within 2 weeks prior to the first dose of medication, patients who have received traditional Chinese patent medicine for anti-tumor adaptation.
• • Patients who have previously received immune checkpoint inhibitors (e.g., anti PD-1 antibodies, anti PD-L1 antibodies, anti CTLA-4 antibodies, etc.) or any treatment targeting tumor immune mechanisms (e.g., antibodies targeting ICOS, CD40, CD137, GITR, OX40 targets, etc.).
• • Within 4 weeks prior to the first dose of medication, patients who have undergone major surgery (determined by the investigator), open biopsy, or significant trauma; or patients who require major surgical treatment during the study period and cannot tolerate medication.
• • Patients with active or potentially recurrent autoimmune diseases; the following are excluded: vitiligo, alopecia, psoriasis, or eczema that do not require systemic treatment; hypothyroidism caused by autoimmune thyroiditis, requiring only stable dose hormone replacement treatment; type I diabetes requiring only stable dose insulin replacement treatment.
• • Within 14 days prior to the first dose of medication, patients who require systemic treatment with \>10 mg/day prednisone or equivalent doses of glucocorticoid hormones or other immunosuppressive drugs; within 4 weeks prior to the first dose of medication, patients with severe infections, including but not limited to complications requiring hospitalization, sepsis, or severe pneumonia.
• • Active or potentially recurrent systemic infections requiring systemic treatment (including active pulmonary tuberculosis and active syphilis infection), and who have used systemic antibacterial, antiviral, or antifungal drugs within 2 weeks prior to the first dose of medication; note: antiviral drugs for hepatitis B are excluded.
• • Active hepatitis B virus carriers, non-active or asymptomatic hepatitis B virus (HBV) carriers (hepatitis B surface antigen \[HBsAg\] positive) with HBV DNA \>1000 IU/mL, and active hepatitis C virus carriers (note: non-active or asymptomatic carriers, after treatment and stable hepatitis B carriers with HBV DNA ≤ 1000 IU/mL are allowed to enroll). Patients with cured hepatitis C are allowed to enroll.
• • Patients with active or a history of inflammatory bowel disease (e.g. Crohn's disease, ulcerative colitis), active diverticulitis, presence of clinical manifestations of gastrointestinal obstruction, or those requiring routine parenteral fluid, parenteral nutrition, or nasogastric tube placement.
• • Severe cerebrovascular or cerebrovascular diseases. Previous antineoplastic treatment toxicity not resolved, defined as toxicity not recovered to NCI CTCAE v5.0 ≤1 grade, or the levels specified in the inclusion/exclusion criteria (except for alopecia).
• • Patients allergic to the investigational medication. Any condition that the investigator believes may pose a risk to receiving study medication treatment, or may interfere with the evaluation of the study medication or the safety or interpretation of the results of the study (e.g. patients with other serious diseases or psychiatric disorders, etc.)