Induction Immunotherapy Combined With Chemotherapy Followed by Concurrent Chemoradiotherap and Immunotherapy for Advanced Cervical Cancer: An Open-Label, Single-Arm, Phase II Trial
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 34
- 试验地点
- 1
- 主要终点
- Overall response rate
研究概览
简要总结
To explore the efficacy and tolerability of a platinum-based regimen combined with the PD-1 antibody toripalimab administered prior to concurrent chemoradiotherapy in patients with locally advanced cervical cancer.
详细描述
At the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, investigators reported that neoadjuvant camrelizumab combined with induction chemotherapy, followed by camrelizumab plus concurrent chemoradiotherapy and subsequent camrelizumab maintenance, achieved an overall response rate of 100 % in patients with locally advanced cervical cancer, with an acceptable safety profile.
Pre-clinical studies have suggested that concurrent chemoradiotherapy may dampen immune activation in cervical cancer, including reductions in the CD4+/CD8+ T-cell ratio and decreased T-cell receptor (TCR) diversity. These findings imply that administration of immunotherapy prior to chemoradiotherapy might be more effective than giving it concomitantly or afterwards.
Informed by these clinical and translational data, we propose to conduct an initial, prospective phase II trial to evaluate the efficacy and safety of neoadjuvant chemo-immunotherapy followed by concurrent chemoradiotherapy plus immunotherapy in patients with locally advanced cervical cancer, thereby laying the groundwork for a subsequent phase III investigation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Women aged 18-75 years.
- •Histologically confirmed, previously untreated locally advanced cervical cancer of squamous, adenocarcinoma, or adenosquamous type.
- •At least one measurable lesion that has not received prior local therapy (non-nodal lesion ≥ 10 mm longest diameter or pathological lymph node ≥ 15 mm short axis, per RECIST 1.1).
- •Eastern Cooperative Oncology Group (ECOG) Performance Status 0-
- •Estimated life expectancy ≥ 6 months.
- •Investigator-assessed eligibility for concurrent chemoradiotherapy.
- •No clinically significant active bleeding.
- •Laboratory values: WBC > 4 × 10⁹/L; platelets > 100 × 10⁹/L.
- •No history of other malignancies.
- •Women of child-bearing potential must have a negative serum pregnancy test and use effective contraception throughout the study.
- •Written informed consent obtained prior to any study-related procedures.
排除标准
- •Tumor recurrence or distant metastasis at screening.
- •Active autoimmune disease requiring systemic therapy, or any chronic condition requiring long-term high-dose corticosteroids (≥10 mg/day prednisone or equivalent) or other immunosuppressive agents.
- •Systemic corticosteroids (>10 mg/day prednisone or equivalent) or any other immunosuppressive drugs within 14 days before first study dose or anticipated during the study.
- •Live-attenuated vaccination within 30 days before first dose or planned during the study.
- •Prior organ transplantation or known HIV infection.
- •Active hepatitis B (HBV DNA >2000 IU/mL or >10⁴ copies/mL, or HBsAg positive) or active hepatitis C (HCV RNA >10³ copies/mL); co-infection with both viruses is also excluded.
- •Prior therapy with any agent targeting PD-1, PD-L1, PD-L2, CD137, CTLA-4 (e.g., ipilimumab), or any other antibody or drug that modulates T-cell co-stimulation or checkpoint pathways.
- •Known hypersensitivity to monoclonal antibodies, fusion proteins, or any excipients in the investigational products.
- •History of another malignancy within the past 5 years, except adequately treated cervical carcinoma in situ, basal-cell carcinoma of the skin, or other localized malignancies considered cured.
- •Severe non-surgical comorbidity or acute infection.
- •Peripheral neuropathy > Grade 1 (NCI-CTCAE).
- •Inadequate hematologic or organ function:
- •WBC < 4.0 × 10⁹/L, ANC < 1.5 × 10⁹/L, platelets < 100 × 10⁹/L, Hb < 90 g/L
- •TBIL > 1.5 × ULN, ALT/AST > 2.5 × ULN, BUN > 1.5 × ULN, creatinine > 1.5 × ULN
- •Symptomatic brain metastases.
- •Clinically significant cardiac arrhythmias, myocardial ischemia, severe conduction block, heart failure, or severe valvular disease.
- •Severe bone-marrow failure.
- •Uncontrolled psychiatric illness.
- •Pregnant or lactating women.
- •Investigator-judged unsuitability for the trial.
- •Concurrent participation in another interventional clinical study.
研究组 & 干预措施
PD-1 arm
Induction PD-1 inhibitor followed by PD-1 maintenance administered concurrently with chemoradiotherapy and continued after completion.
干预措施: Toripalimab (Drug)
PD-1 arm
Induction PD-1 inhibitor followed by PD-1 maintenance administered concurrently with chemoradiotherapy and continued after completion.
干预措施: Pelvic External-Beam Radiotherapy (EBRT) (Radiation)
结局指标
主要结局
Overall response rate
时间窗: 1 year
The proportion of patients with at least one tumor scan of complete response (CR) or partial response (PR) using RECIST v1.1
次要结局
- Overall survival(3 year)
- Disease Free Survival(3 year)