Neoadjuvant chemoimmunotherapy and surgery for early-stage cervical cancer

Neoadjuvant Chemotherapy Plus Cadunilizumab Followed by Extrafascial Hysterectomy for FIGO Stage IB2 Cervical Cancer: a Multicenter, Single-arm, Phase 2 Trial.

This study is testing if a new treatment combining chemotherapy and immunotherapy before surgery can help women with early-stage cervical cancer do better and have fewer complications.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 50 (estimated)
• Ages: 18 Years to 70 Years
• Sex: Female
• Sponsor: Tongji Hospital (Academic / other)
• Drugs / interventions: immunotherapy, prednisone, Cemiplimab, Cadonilimab, chemotherapy
• Locations: 2 sites (Wuhan, Hubei and 1 other locations)
• Trial ID: NCT06289751 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the feasibility of combining neoadjuvant chemoimmunotherapy with extrafascial hysterectomy and pelvic lymph node dissection in patients diagnosed with stage IB2 cervical cancer. The study aims to evaluate the treatment response rate, monitor adverse effects and complications, and assess the overall survival rate of participants. By utilizing a combination of chemotherapy agents and immunotherapy, the trial seeks to improve outcomes while potentially reducing the complications associated with traditional surgical approaches.

Who should consider this trial

Good fit: Ideal candidates for this study are women aged 18 to 70 with untreated stage IB2 cervical cancer and positive PD-L1 expression.

Not a fit: Patients with advanced cervical cancer or those who do not meet the eligibility criteria, such as those with negative PD-L1 expression, may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could enhance treatment efficacy and reduce surgical complications for patients with early-stage cervical cancer.

How similar studies have performed: While the combination of chemoimmunotherapy and surgery is a novel approach, similar studies have shown promise in improving outcomes for various cancers.

Eligibility criteria

Inclusion Criteria:

1. Clinical diagnosis of untreated stage IB cervical cancer with IB2 (FIGO, 2018 criteria; staging determined by two physicians of associate seniority or higher after gynecologic examination and imaging evaluation);
2. At least one measurable lesion at baseline according to RECIST 1.1 criteria, with lesion size based primarily on magnetic resonance imaging;
3. Pathologically confirmed diagnosis of cervical cancer, including cervical squamous cell carcinoma (any grade), usual type adenocarcinoma (G1 or G2 / Silva A or B), and adenosquamous carcinoma (G1 or G2);
4. Positive PD-L1 expression, Combined Positive Score (CPS) ≥1;
5. Patient age ≥18 years and ≤70 years;
6. ECOG score ≤1;
7. Laboratory tests: WBC ≥3. 5×109/L, NEU ≥1. 5×109/L, PLT ≥100×109/L, serum bilirubin ≤1.5 times the upper limit of normal, aminotransferase ≤1.5 times the upper limit of normal, and BUN and Cr ≤normal;
8. Be willing to follow up and good compliance;
9. Be willing to sign the informed consent, including compliance with the requirements and restrictions listed in the informed consent and program.

Exclusion Criteria:

1. Subjects with an active, known, or suspected autoimmune disease, or a history of an autoimmune disease, except for the following: vitiligo, alopecia areata, Graves's disease, psoriasis, or eczema that has not required systemic therapy within the last 2 years, hypothyroidism that is asymptomatic or requires only stable doses of hormone replacement therapy (due to autoimmune thyroiditis), type 1 diabetes that requires only stable doses of insulin replacement therapy, asthma that subsides completely in childhood and does not require intervention in adulthood, or diseases that do not recur in the absence of external triggers;
2. Prior treatment with immune checkpoint inhibitors, including, but not limited to, other anti-PD-1, anti-PD-L1 antibodies, CTLA-4 antibodies, or antibodies against immune co-stimulators (e.g., antibodies against ICOS, CD40, CD137, GITR, OX40 targets, etc.), or any other therapy targeting a mechanism of tumor immune action;
3. Known hypersensitivity to any component and/or any excipient of the trial prescribed medication;
4. Immunosuppressive drugs or systemic corticosteroids for immunosuppression (\> 10 mg/day of prednisone or other equivalent) within 2 weeks prior to trial dosing; topical, ophthalmic, intra-articular, intranasal, and inhaled corticosteroids are permitted;
5. Received herbs with antitumor effects or drugs with immunomodulatory effects (e.g., thymidine, interferon, interleukin-2) within 2 weeks prior to the trial;
6. Active systemic infection requiring systemic treatment;
7. Serious infection within 4 weeks prior to the first dose, including but not limited to complications requiring hospitalization, sepsis, or severe pneumonia;
8. Patients with untreated chronic hepatitis B, or HBV carriers with chronic hepatitis B virus (HBV) DNA greater than 1,000 IU/mL, or patients with active hepatitis C. Inactive HBsAg carriers, patients with hepatitis B who have received treatment and are in stable condition (HBV DNA \< 1000 IU/mL), and patients with cured hepatitis C are eligible for enrollment.HCV antibody-positive subjects will be eligible for the study only if they have a negative HCV RNA test;
9. Known active tuberculosis (TB), patients with suspected active TB should undergo chest X-ray and sputum examination in conjunction with clinical signs and symptoms for exclusion;
10. Immunodeficiency or human immunodeficiency virus (HIV antibody positive);
11. Subjects with active inflammatory bowel disease or a history of such disease (e.g., Crohn's disease, ulcerative colitis, or chronic diarrhea). Subjects who are unable to swallow or who have malabsorption syndrome, uncontrolled nausea, vomiting, diarrhea, or other gastrointestinal disorders that severely interfere with drug intake and absorption;
12. Known interstitial lung disease that is symptomatic or may interfere with detection or treatment of immune-associated pneumonia;
13. Treatment with a live or attenuated vaccine administered within 4 weeks prior to the first trial dose, inactivated seasonal influenza virus vaccine is permitted;
14. Patients who have received a prior allogeneic bone marrow transplant or solid organ transplant;
15. History of primary malignant tumor within the last 5 years;
16. Subjects who have undergone major surgery (e.g., open abdomen, open chest, organ resection, etc.) and severe trauma within 28 days prior to the first dose of the implantable infusion device is permitted;
17. Subjects with a history of gastrointestinal perforation, gastrointestinal fistula, or female genital fistula;
18. Uncontrolled other co-morbidities, symptoms, or medical history, including (i) persons with one of the following cardiovascular diseases or cardiovascular risk factors: myocardial infarction, unstable angina, pulmonary embolism, acute/continuous myocardial ischemia, cerebral vascular accident, transient ischemic attack, or other arterial or venous thrombosis, embolism, or cerebral ischemic event of clinical significance/requiring pharmacologic intervention; and persons who have had, within 6 months, a symptoms of congestive heart failure (New York Heart Association (NYHA) class III and above); (ii) clinically significant bleeding symptoms or a history of significant bleeding characteristics such as gastrointestinal bleeding, gastric ulcer bleeding, or vasculitis within 1 month prior to the first dose; (iii) clinically active hemoptysis, active diverticulitis, abdominal abscesses, and gastrointestinal obstruction; and (iv) uncontrolled pleural effusion, pericardial effusion, or ascites requiring Repeated drainage of ascites; ⑤ Abnormal liver or kidney development or history of surgery;
19. Pregnant or breastfeeding female patients; women of childbearing age who refuse to accept contraceptive measures during neoadjuvant immunotherapy;
20. Concurrent participation in other interventional clinical trials; participation in observational, non-interventional clinical trials is permitted;
21. Any condition that, in the opinion of the investigator, may result in risk in receiving the study drug or that would interfere with the evaluation of the safety of the study drug or the interpretation of the study results.

Where this trial is running

Wuhan, Hubei and 1 other locations

• Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology — Wuhan, Hubei, China (Recruiting)
• Qilu Hospital of Shandong University — Jinan, Shandong, China (Recruiting)

Study contacts

• Study coordinator: Gang Chen

Conditions Cervical Cancer; Neoadjuvant Chemoimmunotherapy; Radical Hysterectomy; Extrafascial Hysterectomy