An Open-label, Phase 2 Randomized Trial of Camrelizumab (SHR1210) Plus Apatinib Versus Paclitaxel and Cisplatin/Carboplatin Plus Bevacizumab as a First-line Therapy in Patients With Stage IVB, Recurrent, or Persistent Cervical Cancer
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 35
- 试验地点
- 2
- 主要终点
- Progression-Free Survival (PFS)
研究概览
简要总结
Cervical cancer is the second-most common cancer in the world and is a leading cause of cancer death among women in developing countries. Cisplatin-based chemotherapy +/- bevacizumab have been recommended as the first-line treatment for patients who present with metastatic (e.g. stage IVB), persistent, or recurrent cervical cancer. However, patients in this setting are rarely curable. The immune checkpoint inhibitor (ICI) therapy, including cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed death-1 (PD-1), and programmed death-ligand 1 (PD-L1) inhibitors, has revolutionized the treatment of several cancers. The investigator previously reported the promising antitumor efficacy of camrelizumab (PD-1 inhibitor) combined with apatinib (VEGFR2 inhibitor) as second-line, or later, therapy in patients with advanced cervical cancer. This randomized study is to assess the efficacy and safety of first-line treatment with camrelizumab plus apatinib compared to the efficacy and safety of paclitaxel and cisplatin/carboplatin plus bevacizumab in patients with stage IVB, recurrent, or persistent cervical cancer.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Signed Informed Consent Form (ICF)
- •Age ≥ 18 years and ≤ 70 years
- •Patients must have primary stage IVB, recurrent or persistent squamous cell carcinoma of the cervix which has not been treated with systemic chemotherapy and is not amenable to curative treatment with surgery and/or radiation therapy NOTE: Prior adjuvant therapy is NOT counted as a systemic chemotherapeutic regimen for management of recurrent, persistent or metastatic carcinoma of the cervix; adjuvant therapy includes cisplatin given concurrent with primary radiation therapy (CCRT) and adjuvant chemotherapy given following the completion of concurrent chemotherapy and radiation therapy
- •Patients must have measurable disease per RECIST v1.1; measurable lesions are defined as those that can be accurately measured in at least one dimension (longest diameter to be recorded as ≥ 10 mm with computed tomography (CT) scan, magnetic resonance imaging (MRI); a lymph node must be ≥ 15 mm in short axis. Tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy.
- •Life expectancy exceeds 12 weeks.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Has the ability to swallow pills
- •Provide cervical cancer tissue (archival or fresh biopsy specimen) prior to randomization for PD-L1 immunohistochemistry (IHC) testing by central laboratory
- •Has PD-L1 IHC CPS ≥ 1 by central laboratory testing
- •Has adequate organ function
- •Female participants must not be pregnant, not breastfeeding. Female participants of childbearing potential should be willing to use one acceptable contraception (i.e., oral contraceptives, contraceptive injections, contraceptive implants, spermicides, condoms, intrauterine devices [IUDs]) during the treatment period and for 180 days following the end
排除标准
- •Has an active autoimmune disease that has required systemic treatment; replacement therapy is not considered a form of systemic treatment.
- •Concurrent medical condition requiring the use of immunosuppressive medications, or immunosuppressive doses of systemic or absorbable topical corticosteroids. Doses > 10 mg/day prednisone or equivalent are prohibited within 2 weeks before study drug administration.
- •Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis;
- •Has pleural effusion and ascites that require punctured and drained. However, an exception includes patients with pleural effusion and ascites who have no symptoms.
- •Has bilateral hydronephrosis which cannot be alleviated by ureteral stents or percutaneous drainage. Ureteral stent placement must be performed in patients with unilateral hydronephrosis prior to enrollment.
- •Patients with a prior invasive malignancy who have had any evidence of disease within the last 5 years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.
- •Clinically significant cardiovascular diseases, including but not limited to congestive heart failure (New York heart association (NYHA) class > 2), unstable or severe angina, severe acute myocardial infarction, or cardiac arrhythmia requiring medical intervention within 6 months before enrollment.
- •Prior or concurrent diagnosis of idiopathic pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, and active pneumonia detected by CT during the screening period.
- •Hypertension that can not be well controlled through antihypertensive drugs (systolic pressure ≥ 140 mm Hg and/or diastolic pressure ≥ 90 mm Hg)
- •Proteinuria ≥ (++) or 24 hours total urine protein > 1.0 g.
- •Patients have coagulation abnormalities with a tendency to bleed or are receiving thrombolytic or anticoagulant therapy. Prophylactic use of aspirin (≤100mg/d), low-molecular-weight-heparin (≤40mg/d), and Rivaroxaban is permitted.
- •Any hemorrhage or bleeding event ≥ CTCAE Grade 2 within 4 weeks prior to the first dose of study intervention;
- •Arterial thrombus or phlebothrombosis within 6 months prior to randomization.
- •Gastrointestinal fistula, bladder/ureteral fistula, or intestinal obstruction within 6 months prior to randomization
- •Has radiation-induced enteritis within 12 months prior to randomization
- •Has received anticancer treatment, including but not limited to radiotherapy, chemotherapy, and surgery within 4 weeks before the first dose of study intervention
- •Any unresolved toxicities (i.e., ≤ Grade 1 or at baseline) from prior therapy, with exception of alopecia;
- •Has an active infection requiring systemic therapy or baseline white blood cells >1.5 × 10 9 / L;
- •Has known active hepatitis B disease (hepatitis B virus [HBV] DNA > 500 IU/ml 1000 copies/ml) or hepatitis C disease;
- •Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibody, apatinib, and bevacizumab.
- •Has a known history of human immunodeficiency virus (HIV) infection;
- •Pregnant or breastfeeding.
- •According to the judgement of the researchers, there are other factors that may lead to the termination of the study.
研究组 & 干预措施
Paclitaxel + Cisplatin/Carboplatin + Bevacizumab
On Day 1 of each 21-day cycle, participants receive an intravenous (IV) infusion of paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH bevacizumab 15 mg/kg OR paclitaxel 175 mg/m^2 PLUS carboplatin Area Under the Curve (AUC) 5, WITH bevacizumab 15 mg/kg). All treatments are administered until disease progression or unacceptable toxicity.
干预措施: Paclitaxel (Drug)
Camrelizumab + Apatinib
On Day 1 and Day 15 of each 28-day cycle, participants receive an intravenous (IV) infusion of camrelizumab 200 mg Plus an oral apatinib 250 mg once daily. Apatinib will be administered 250 mg once every other day when completing twice tumor assessement. All treatments are administered until disease progression or unacceptable toxicity.
干预措施: Camrelizumab (Drug)
Camrelizumab + Apatinib
On Day 1 and Day 15 of each 28-day cycle, participants receive an intravenous (IV) infusion of camrelizumab 200 mg Plus an oral apatinib 250 mg once daily. Apatinib will be administered 250 mg once every other day when completing twice tumor assessement. All treatments are administered until disease progression or unacceptable toxicity.
干预措施: Apatinib (Drug)
Paclitaxel + Cisplatin/Carboplatin + Bevacizumab
On Day 1 of each 21-day cycle, participants receive an intravenous (IV) infusion of paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH bevacizumab 15 mg/kg OR paclitaxel 175 mg/m^2 PLUS carboplatin Area Under the Curve (AUC) 5, WITH bevacizumab 15 mg/kg). All treatments are administered until disease progression or unacceptable toxicity.
干预措施: Cisplatin (Drug)
Paclitaxel + Cisplatin/Carboplatin + Bevacizumab
On Day 1 of each 21-day cycle, participants receive an intravenous (IV) infusion of paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH bevacizumab 15 mg/kg OR paclitaxel 175 mg/m^2 PLUS carboplatin Area Under the Curve (AUC) 5, WITH bevacizumab 15 mg/kg). All treatments are administered until disease progression or unacceptable toxicity.
干预措施: Carboplatin (Drug)
Paclitaxel + Cisplatin/Carboplatin + Bevacizumab
On Day 1 of each 21-day cycle, participants receive an intravenous (IV) infusion of paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH bevacizumab 15 mg/kg OR paclitaxel 175 mg/m^2 PLUS carboplatin Area Under the Curve (AUC) 5, WITH bevacizumab 15 mg/kg). All treatments are administered until disease progression or unacceptable toxicity.
干预措施: Bevacizumab (Drug)
结局指标
主要结局
Progression-Free Survival (PFS)
时间窗: up to 36 months
PFS defined as the time from randomization to the first documented disease progression per RECIST v1.1, or death due to any cause, whichever occurs first.
次要结局
- Objective Response Rate (ORR)(up to 24 months)
- Duration of Response (DOR)(up to 24 months)
- Number of Subjects with treatment-related adverse events (AEs)(up to 48 months)
- Disease Control Rate (DCR)(up to 24 months)
- Overall Survival (OS)(up to 48 months)
- Patient-reported outcomes (PROs)(up to 48 months)
研究者
Chunyan Lan，MD
Professor
Sun Yat-Sen University Cancer Center