An Open-label, Randomized, Multicenter Comparative Study of the Pharmacokinetics, Safety, and Efficacy of RPH-002 and Erbitux® in Patients With Unresectable Metastatic or Recurrent Head and Neck Squamous Cell Carcinoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 118
- 试验地点
- 18
- 主要终点
- Area under the pharmacokinetic curve "concentration-time" (AUC(0-168)) of cetuximab
研究概览
简要总结
The primary objective of this clinical study is to compare the pharmacokinetic parameters of drugs RPH-002 and Erbitux® after a single intravenous administration, as well as to evaluate the safety of drug RPH-002 in comparison with drug Erbitux® when used in combination with Docetaxel and Cisplatin as first-line therapy in patients with Recurrent Head and Neck Squamous Cell Carcinoma. In addition, this study will include a comparative assessment of immunogenicity and a pilot evaluation of efficacy
详细描述
This study is a multicenter, open-label, randomized Phase I study
This clinical study includes the following stages:
- Stage 1: Evaluation of the pharmacokinetics of drugs RPH-002 and Erbitux® after the first administration, and evaluation of the safety and immunogenicity of drugs RPH-002 and Erbitux® after four administrations of the study therapy
- Stage 2: Evaluation of pharmacokinetics, safety, immunogenicity, and pilot efficacy of drugs RPH-002 and Erbitux® during up to 18 weeks of therapy
- Stage 3: Evaluation of safety, immunogenicity, and pilot efficacy of RPH-002 and Erbitux® after 6 months of therapy, as well as evaluation of safety, immunogenicity, and pilot efficacy of drug RPH-002 after 1 year of therapy
Therapy with cetuximab within this clinical study will continue until disease progression or the development of unacceptable toxicity
Disease progression is defined as the presence of one or more of the following criteria:
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
盲法说明
Open label
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Main Period (Period 1)
- •A voluntarily signed and dated Informed Consent form (ICF) of the patient
- •Histologically confirmed squamous cell carcinoma of the head and neck
- •Body mass index (BMI) between 18 and 30 kg/m^2, inclusive
- •Documented unresectable locoregional recurrence or distant metastases, or progression after prior chemoradiotherapy or combination therapy completed >3 months before screening, not amenable to local treatment (except cases with high risk of tumor lysis or bleeding), or newly diagnosed metastatic disease not previously treated with systemic therapy. Study treatment is first-line therapy
- •At least one measurable lesion per RECIST 1.1
- •Karnofsky performance status ≥70%
- •Screening laboratory values within the following limits (per local lab normal ranges):
- •Hemoglobin ≥90 g/L
- •Leukocytes ≥3.0 × 10^9/L
- •Neutrophils ≥1.5 × 10^9/L
- •Platelets ≥100 × 10^9/L
- •Total bilirubin ≤2 × Upper Limit of Normal (ULN)
- •Aspartate aminotransferase (AST) ≤3 × ULN
- •Alanine aminotransferase (ALT) ≤3 × ULN
- •Estimated glomerular filtration rate (eGFR) ≥60 mL/min
- •Men and women of childbearing potential, and women within 2 years of menopause, must agree to use reliable contraception from informed consent through at least 6 months after study treatment; women of childbearing potential must have a negative urine pregnancy test. Women with no reproductive potential (≥2 years post-menopause or surgically sterile) are exempt
- •Ability and willingness to comply with study protocol and procedures for the planned duration of participation
- •Ability to undergo required pharmacokinetic sample collection, as judged by the investigator
- •Maintenance Therapy Period (Period 2)
- •Documented tumor response or disease stabilization per RECIST 1.1 by computed tomography (CT) or magnetic resonance imaging (MRI) at Week 18 of the Main Period
- •Ability and willingness to provide written informed consent for participation in Period 2
- •Karnofsky performance status ≥ 70%
- •Laboratory values within the following limits (per local lab normal ranges):
- •Hemoglobin ≥ 90 g/L
- •Leukocytes ≥ 3.0 × 10^9/L
- •Neutrophils ≥ 1.5 × 10^9/L
- •Platelets ≥ 100 × 10^9/L
- •Total bilirubin ≤ 2 × ULN (upper limit of normal)
- •AST ≤ 3 × ULN
- •ALT ≤ 3 × ULN
- •eGFR ≥ 60 mL/min
- •Men and women of childbearing potential, and women within 2 years of menopause, must agree to use reliable contraception from informed consent through at least 6 months after study treatment; women of childbearing potential must have a negative urine pregnancy test. Women with no reproductive potential (≥2 years post-menopause or surgically sterile) are exempt
排除标准
- •Main Period (Period 1)
- •Prior therapy with cetuximab or other monoclonal antibody-based biologics
- •Chemotherapy, radiotherapy, or surgery for head and neck cancer within 3 months before screening
- •Any other surgery (except biopsy, implantable venous port placement, or urgent non-cancer surgery) within 3 months before screening
- •Nasopharyngeal carcinoma
- •Other malignancy within the past 5 years or prior/concurrent squamous cell carcinoma (except cured in situ ductal carcinoma, cervical carcinoma in situ, basal cell or squamous cell skin cancer)
- •Expected survival < 3 months
- •Women who are pregnant or breastfeeding, or unwilling to use effective contraception during the study and for at least 6 months after
- •Significant cardiovascular disease per investigator, including uncontrolled hypertension (systolic ≥180 mmHg or diastolic ≥130 mmHg), coronary artery disease, myocardial infarction within 12 months, high-risk uncontrolled arrhythmias, or uncontrolled heart failure
- •Active infection requiring systemic antibiotic therapy
- •Ongoing systemic immunotherapy, hormone therapy, or other cancer treatments not specified in the protocol within 6 months prior to screening or during the study
- •Known or suspected brain metastases, including parenchymal, leptomeningeal, or dural involvement associated with symptoms
- •Positive screening for HBsAg, anti-HCV, anti-HIV1/2 antibodies, or syphilis within 3 months prior to screening
- •Conditions preventing compliance with the study protocol per investigator
- •Participation in another investigational drug study within 6 months prior to screening
- •Unstable medical conditions, including uncontrolled diabetes, psychiatric disorders, or uncontrolled seizures, that could interfere with protocol adherence
- •Known hypersensitivity to any component of study therapy or combination chemotherapy drugs
- •Excessive alcohol use (>10 standard drinks/week) or history of alcoholism or substance abuse associated with symptoms. One standard drink = 250 mL beer, 125 mL wine, or 30 mL spirits
- •Maintenance Therapy Period (Period 2)
- •No documented tumor response or disease stabilization per RECIST 1.1 by CT or MRI at Week 18 of the Main Period
- •Women who are pregnant or breastfeeding, or unwilling to use effective contraception during the study and for at least 6 months after
- •Significant cardiovascular disease per investigator, including uncontrolled hypertension (systolic ≥180 mmHg or diastolic ≥130 mmHg), coronary artery disease, myocardial infarction within 12 months, high-risk uncontrolled arrhythmias, or uncontrolled heart failure
- •Active infection requiring systemic antibiotics
- •Ongoing systemic immunotherapy, hormone therapy, or other cancer treatments not specified in the protocol for Period 2
- •Known or suspected brain metastases, including parenchymal, leptomeningeal, or dural involvement associated with symptoms
- •Conditions preventing compliance with study procedures per investigator
- •Participation in another investigational drug study
- •Unstable medical conditions, including uncontrolled diabetes, psychiatric disorders, or uncontrolled seizures, that could interfere with protocol adherence
- •Excessive alcohol use (>10 standard drinks/week) or history of alcoholism or substance abuse associated with symptoms. One standard drink = 250 mL beer, 125 mL wine, or 30 mL spirits
研究组 & 干预措施
RPH-002 + docetaxel + cisplatin
Patients receive RPH-002 in combination with docetaxel and cisplatin during the Main Period (up to 18 weeks, 6 cycles) and RPH-002 monotherapy during the Maintenance Period (up to 36 weeks), or until disease progression or unacceptable toxicity
干预措施: RPH-002 (Drug)
RPH-002 + docetaxel + cisplatin
Patients receive RPH-002 in combination with docetaxel and cisplatin during the Main Period (up to 18 weeks, 6 cycles) and RPH-002 monotherapy during the Maintenance Period (up to 36 weeks), or until disease progression or unacceptable toxicity
干预措施: cisplatin (Drug)
RPH-002 + docetaxel + cisplatin
Patients receive RPH-002 in combination with docetaxel and cisplatin during the Main Period (up to 18 weeks, 6 cycles) and RPH-002 monotherapy during the Maintenance Period (up to 36 weeks), or until disease progression or unacceptable toxicity
干预措施: docetaxel (Drug)
Erbitux® + docetaxel + cisplatin
Patients receive Erbitux® in combination with docetaxel and cisplatin during the Main Period (up to 18 weeks, 6 cycles) and Erbitux® monotherapy during the Maintenance Period (up to 36 weeks), or until disease progression or unacceptable toxicity
干预措施: Erbitux® (Drug)
Erbitux® + docetaxel + cisplatin
Patients receive Erbitux® in combination with docetaxel and cisplatin during the Main Period (up to 18 weeks, 6 cycles) and Erbitux® monotherapy during the Maintenance Period (up to 36 weeks), or until disease progression or unacceptable toxicity
干预措施: cisplatin (Drug)
Erbitux® + docetaxel + cisplatin
Patients receive Erbitux® in combination with docetaxel and cisplatin during the Main Period (up to 18 weeks, 6 cycles) and Erbitux® monotherapy during the Maintenance Period (up to 36 weeks), or until disease progression or unacceptable toxicity
干预措施: docetaxel (Drug)
结局指标
主要结局
Area under the pharmacokinetic curve "concentration-time" (AUC(0-168)) of cetuximab
时间窗: Pre-dose on Day 1 (first administration) and 1, 2, 3, 4, 6, 12, 24, 48, 96, 168 hours post-dose
Area under the pharmacokinetic curve "concentration-time" of cetuximab after the first (single dose) administration, truncated at the point before the second administration, i.e. up to 168 hours
Proportion of patients (%) with adverse drug reactions (ADRs) of any severity
时间窗: Up to Day 365
Proportion of patients (%) with adverse drug reactions (ADRs) of any severity
次要结局
- Proportion of patients (%) who required discontinuation of treatment due to development of ADRs(Up to Day 365)
- Proportion of patients (%) with ADRs of severity grade ≥ 3(Up to Day 365)
- Maximum serum concentration of cetuximab after the first administration (Cmax)(Pre-dose on Day 1 (first administration) and 1, 2, 3, 4, 6, 12, 24, 48, 96, 168 hours post-dose)
- Maximum serum concentration of cetuximab at steady state (Cmax ss)(Pre-dose on Day 22 (fourth infusion) and 1, 2, 3, 4, 6, 12, 24, 168 hours post-dose)
- Minimum serum concentration of cetuximab at steady state (Cmin ss)(Within 30 ± 10 minutes prior to dosing at Visits 3 (Day 15), 5 (Day 29), 6 (Day 36), 7 (Day 43), 8 (Day 50), 9 (Day 57), 12 (Day 78), 15 (Day 99), and 18 (Day 120))
- Area under the pharmacokinetic curve "concentration-time" of cetuximab at steady state (AUC tau)(Pre-dose on Day 22 (fourth infusion) and 1, 2, 3, 4, 6, 12, 24, 168 hours post-dose)
- Proportion of patients (%) with adverse events (AEs) of any severity(Up to Day 365)
- Proportion of patients (%) with AEs of severity grade ≥ 3(Up to Day 365)
- Proportion of patients (%) with serious adverse events (SAEs)(Up to Day 365)
- Proportion of patients (%) with serious adverse drug reactions (SADRs)(Up to Day 365)
- Proportion of patients (%) who developed anti-drug antibodies (ADA) to cetuximab(Pre-dose in Period 1 on Days 1, 15, 29, 57, and 85, and 28 ± 3 days post-last infusion; pre-dose in Period 2 on Days 6, 12, 18, 24, 30, and 36)
- Proportion of patients (%) who developed neutralizing antibodies (NAb) to cetuximab(Pre-dose in Period 1 on Days 1, 15, 29, 57, and 85, and 28 ± 3 days post-last infusion; pre-dose in Period 2 on Days 6, 12, 18, 24, 30, and 36)