Utidelone Combined With Toripalimab in Patients With Pretreated Recurrent or Metastatic Cervical Cancers: a Single-Arm, Phase II Study
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 32
- 试验地点
- 1
- 主要终点
- Objective response rate (ORR)
研究概览
简要总结
This is a Phase II clinical trial to evaluate the safety and efficacy of Utidelone, a genetically engineered epothilone derivative, combined with Toripalimab, a PD-1 inhibitor, in patients with recurrent or metastatic cervical cancer who have progressed after standard treatments. The study will also assess the safety profile of this combination therapy. The primary objectives of this study include: (1) to determine the objective response rate (ORR), meaning whether the treatment can reduce the size of tumors or make them disappear, according to the RECIST 1.1 criteria; (2) to evaluate the safety of the treatment and document the side effects experienced by participants. This study is for individuals who: (1) are between 18 and 75 years old; (2) have a confirmed diagnosis of recurrent or metastatic cervical cancer; (3) have previously received at least one standard chemotherapy regimen that is no longer controlling the cancer; (4) are in generally good health, as determined by the study investigators. In this single-arm study, all participants will receive the same treatment: Utidelone will be administered by intravenous (IV) infusion over 1.5 hours, once a day for 5 consecutive days, in each 21-day treatment cycle; Toripalimab will be administered by IV infusion over 1.5 hours, once on Day 6 of each 21-day cycle. Participants may continue receiving the study drugs as long as they are benefiting from the treatment and side effects are manageable. Doctors will assess tumor size using imaging scans (like CT or MRI) every 6 weeks to monitor how the cancer responds to treatment. The study will take place at Zhongnan Hospital of Wuhan University and plans to include approximately 32 participants.
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
- •Informed Consent: Patients must voluntarily sign an informed consent form prior to any study-related procedures.
- •Age: Aged ≥18 years and ≤75 years.
- •Diagnosis: Histologically or cytologically confirmed recurrent or metastatic cervical carcinoma.
- •Performance Status: With an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to
- •Measurable Disease: With at least one measurable lesion as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.
- •Prior Therapy:
- •Patients must have received at least one line of standard systemic chemotherapy for recurrent/metastatic disease, OR
- •Patients with rapid disease progression (occurring within 6 months) during or after prior neoadjuvant or concurrent chemoradiotherapy.
- •Treatment-Related Toxicity: Recovery from all toxicities related to prior anti-cancer therapies to ≤ Grade 1 (according to CTCAE v5.0). Patients with alopecia of any grade are eligible.
- •Adequate Hematological Function (within 1 week prior to enrollment, per local laboratory reference ranges):
- •White blood cell count (WBC) ≥ 2.5 × 10⁹/L.
- •Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L.
- •Platelet count (PLT) ≥ 100 × 10⁹/L.
- •Hemoglobin (Hb) ≥ 9.0 g/dL (transfusion or erythropoietin use is permitted to meet this criterion).
- •Adequate Liver and Kidney Functions (within 1 week prior to enrollment, per local laboratory reference ranges):
- •Total bilirubin (TBIL) ≤ 1.5 × the upper limit of normal (ULN).
- •Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN (≤ 5 × ULN for patients with liver metastases).
- •Calculated creatinine clearance (Ccr) ≥ 60 mL/min.
- •Contraception: Patients of childbearing potential must agree to use highly effective contraception during the study and for at least 90 days after the last dose of study treatment. A negative serum or urine pregnancy test is required for female patients of childbearing potential within 7 days prior to enrollment.
- •Life Expectancy: Anticipated life expectancy of at least 12 weeks.
- •Compliance: Patients must be able and willing to comply with the study protocol for treatment and follow-up.
排除标准
- •Concurrent Malignancy: History of other active malignancies within the past 5 years, except for adequately treated basal cell carcinoma of the skin.
- •Recent Anti-cancer Therapy: Any anti-cancer therapy (including chemotherapy, radical radiotherapy, hormonal therapy, biological therapy, or anti-cancer Chinese herbal medicine) within 4 weeks prior to the initiation of study treatment.
- •Recent Major Surgery/Trauma: Major surgical procedure (excluding diagnostic biopsy) or significant traumatic injury within 4 weeks prior to the first dose of study drug, or anticipation of the need for major surgery during the study period.
- •Prior Neurotoxicity: History of ≥ Grade 3 neurological adverse reactions attributed to prior anti-microtubule therapy.
- •Symptomatic CNS Metastases: Patients with symptomatic central nervous system (CNS) metastases.
- •Pregnancy/Lactation: Women who are pregnant or breastfeeding.
- •Hypersensitivity: Known or suspected hypersensitivity to any component of the study drugs or their excipients.
- •Severe Comorbidities: Any uncontrolled or severe concurrent medical condition that, in the investigator's judgment, would preclude participation, including but not limited to:
- •Severe cardiovascular or cerebrovascular disease.
- •Uncontrolled diabetes mellitus or hypertension.
- •Active severe infection.
- •Active peptic ulcer disease.
- •Uncontrolled psychiatric illness/disorder.
- •General Exclusion: Any other condition or circumstance that, in the opinion of the investigator, would compromise the patient's safety or compliance, or make the patient unsuitable for study participation.
- •Contraindication to Steroids: Conditions for which corticosteroid use is contraindicated.
研究组 & 干预措施
Utidelone plus Toripalimab
- Drug: Utidelone (1)Dosage: 30 mg/m² (2)Route of Administration: Intravenous drip (IV infusion) (3)Schedule: Administered once daily on Days 1-5 of each cycle. (4)Cycle Duration: 21 days (q3w).
- Drug: Toripalimab (1)Dosage: 240 mg (2)Route of Administration: Intravenous drip (IV infusion) (3)Schedule: Administered on Day 6 of each cycle. (4)Cycle Duration: 21 days (q3w).
干预措施: Utidelone plus Toripalimab (Drug)
结局指标
主要结局
Objective response rate (ORR)
时间窗: Tumor assessments are performed at baseline and every 6 weeks (± 3 days) until progression or start of new therapy. ORR is analyzed after all patients have completed at least 18 weeks of follow-up or experienced a study endpoint event.
次要结局
- Progression-Free Survival (PFS)(From the date of enrollment until first documented disease progression (per RECIST 1.1) or death from any cause, whichever occurs first, assessed up to approximately 24 months.)
- Time to Response (TTR)(From the date of enrollment to the first documented objective response (Complete or Partial Response per RECIST 1.1), assessed up to approximately 24 months.)
- Duration of Response (DoR)(From the date of first documented objective response (CR or PR) until documented disease progression or death due to underlying cervical cancer, assessed up to approximately 36 months.)
- Overall Survival (OS)(From the date of enrollment until death from any cause, assessed up to approximately 36 months.)
- Incidence of Treatment-Emergent Adverse Events (TEAEs)(From the first dose of study drug until 30 days after the last dose, assessed throughout the treatment period (up to approximately 24 months).)
- Incidence of Serious Adverse Events (SAEs)(From the first dose of study drug until 90 days after the last dose, assessed throughout the treatment and extended safety follow-up period (up to approximately 27 months).)
- Number of Participants With Clinically Significant Laboratory Abnormalities(Laboratory parameters are monitored at each 21-day treatment cycle from first dose until 30 days after the last dose (up to approximately 24 months).)
研究者
Hui Qiu
Head of Department
Zhongnan Hospital