NCT05997459尚未招募2 期
A Single Arm, Phase ll Exploratory Clinical Study of Pemetinib in the Treatment of Advanced Gastric Cancer With FGFR Mutation and Previous Standard Treatment Failure
Sun Yat-sen University1 个研究点 分布在 1 个国家目标入组 23 人开始时间: 2023年8月25日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 23
- 试验地点
- 1
- 主要终点
- PFS
研究概览
简要总结
purpose of research： fundamental purpose:
• To evaluate the effectiveness of pemitinib in patients with advanced gastric cancer who have failed standard therapy with fibroblast growth factor receptor 1-3 (FGFR1-3) variant (including but not limited to FGFR1-3 amplification, rearrangement / fusion, mutation, etc.).
Secondary purpose:
- To evaluate the safety and tolerability of pemitinib in patients with advanced gastric cancer who have previously failed standard therapy with the FGFR1-3 variant: including incidence of adverse events (AEs) and serious adverse events (SAEs) and association with therapy. Incidence of treatment-related AEs / SAEs.
- Exploring efficacy and safety in subjects with different FGFR variant types.
The end of the study:
Main end point:
• The primary endpoint of the study was the 6-month PFS rate (progression-free survival, defined as first dose to disease progression [PD] or death).
Secondary end point:
• Objective response rate (defined as the proportion of subjects achieving complete response (CR) or partial response (PR) by RECIST1.1 criteria).
Duration of response (DOR, defined as the time from first CR or PR to PD, is used only for subjects with an objective response).
- Disease control rate (DCR, defined as the proportion of subjects with CR + PR + stable disease stable [SD]).
- Overall survival (OS, defined as the time of first dose to death from any cause).
- Safety and tolerability: Grade evaluation for assessing the severity of adverse events according to NCI CTCAE (version 5.0), including:
- Incidence, severity, and association of all AEs, TRAEs, SAEs, and the study drug;
- Number and proportion of subjects stopping treatment due to the above adverse events;
- Study changes in vital signs, physical examination findings, and laboratory results before, during and after treatment.
- To describe the efficacy and safety in subjects with different FGFR gene variant types.
详细描述
research design: This study is a prospective, single-arm, phase II clinical study. Patients with advanced gastric cancer who had failed standard treatment with FGFR1-3 variant, were included in the study by meeting the inclusion criteria after completing the informed consent. Patients will receive pemitinib 13.5 mg once daily (QD) orally on a 2-week dose / 1-week withdrawal regimen. Subjects will continue treatment until disease progression or intolerable toxicity. Clinical tumor imaging evaluation per RECIST v1.1, every 6 weeks (± 7 days) and every 9 weeks (± 7 days) after 48 weeks. Safety assessment was performed using NCI-CTCAE 5.0.
Pemitinib, dose and mode of administration:
Pemitinib will be treated as a 2 week / 1 week withdrawal regimen, 1 dose, 13.5mg, QD, 21 day cycle. Subjects should be on pometitinib at a fixed time per day to avoid inconsistent effects on plasma concentration.
Sample size and statistical methods:
- In this study, using the 6-month PFS rate as the primary endpoint, Calculted using the confidence interval method of Kapian-Meier estimation, Based on the historical data, The 6-month PFS rate of second-line chemotherapy in subjects with previous first-line treatment was approximately 20% (RAINBOW study, BRIGHTER Study), The 6-month PFS rate in subjects with previous second-line or more treatment was approximately 10% (Attraction-2 study), It is estimated that about 20% of the second-line and above treated subjects will be included in this study, The overall 6-month PFS rate was about 18%, Assuming that the 6-month PFS rate could be improved to 36%, Using the test level as one-sided α =0.1, ß=0.20, After follow-up for at least 6 months, With 80% confidence be observed with a 90% confidence interval lower bound greater than 18%, In total, 23 subjects will need to be enrolled.
- Statistical analysis method: Continuous variables were described by mean, standard deviation, median, minimum and maximum values, and categorical variables were described by frequency and percentage. The proportion of subjects with the ORR and DCR and their 95% CI were estimated. Median PFS, DOR, and OS were estimated using Kaplan-Meier.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Main selection criteria:
- •Written informed consent was signed prior to the implementation of any trial-related process;
- •Age: 18 years old;
- •Advanced gastric cancer was confirmed histologically or cytologically;
- •At least one measurable lesion as per version RECIST v1.1;
- •Histology confirmed the presence of the FGFR1-3 variant, including but not limited to amplification, mutation, fusion / rearrangement;
- •Patients who are tested negative for HER 2 by immunohistochemistry (IHC), or by immunohistochemistry (ICH) and in situ hybridization (ISH);
- •Progressive disease after standard treatment;
- •No previous small molecule multitarget inhibitors containing FGFR pathway (including but not limited to allotinib, lemavatinib, sorafenib, apatinib, etc.);
- •The ECOG physical fitness status is 0-1;
- •Expected survival time of> 3 months;
排除标准
- •Written informed consent was signed prior to the implementation of any trial-related process;
- •Age: 18 years old;
- •Advanced gastric cancer was confirmed histologically or cytologically;
- •At least one measurable lesion as per version RECIST v1.1;
- •Histology confirmed the presence of the FGFR1-3 variant, including but not limited to amplification, mutation, fusion / rearrangement;
- •Patients who are tested negative for HER 2 by immunohistochemistry (IHC), or by immunohistochemistry (ICH) and in situ hybridization (ISH);
- •Progressive disease after standard treatment;
- •No previous small molecule multitarget inhibitors containing FGFR pathway (including but not limited to allotinib, lemavatinib, sorafenib, apatinib, etc.);
- •The ECOG physical fitness status is 0-1;
- •Expected survival time of> 3 months;
- •For icient organ function for the following laboratory indicators:
- •In the absence of granulocyte colony-stimulating factor for the last 14 days (ANC)≥1.5x109/L；
- •In the last 14 days without blood transfusion, platelets 100109/L；
- •Hemoglobin> 9 g/dL without blood transfusion or erythropoietin in the last 14 days;
- •Total bilirubin 1.5 upper limit of normal (ULN); or total bilirubin> ULN but direct bilirubin ULN;
- •Asparpartate aminotransferase (AST), alanine transaminotransferase (ALT) at 2.5 ULN (ALT or AST 5 ULN is allowed in patients with liver metastasis);
- •Blood creatinine of 1.5 ULN and creatinine clearance (calculated using the Cockcroft-Gault formula) of 50 ml / min;
- •The coagulation function is good, defined as the international normalized ratio (INR) or prothrombin time (PT) 1.5 times ULN; if the subject is undergoing anticoagulant therapy, as long as the PT is within the proposed range of the anticoagulant
- •For female subjects of childbearing age, a urine or serum pregnancy test within 3 days prior to the first dose of study drug (cycle 1 Day 1, was negative). If the urine pregnancy test results cannot be confirmed as negative, a blood pregnancy test is required. Non-childbearing women were defined as at least 1 year after menopause, or had undergone surgical sterilization or hysterectomy;
- •If there is a risk of conception, all subjects (either male or female) should have an annual failure rate below 1% for the entire treatment period until 120 days after the last dose of study drug (or 180 days after the last dose of chemotherapy drug).
- •Main exclusion criteria:
- •Other malignant diseases other than digestive tract tumors diagnosed within 5 years before the first dose (excluding radical skin basal cell carcinoma, skin squamous epithelial carcinoma, and / or radical resection);
- •Previous selective FGFR inhibitor therapy;
- •Have received any other study drug or attended an interventional clinical investigator within 28 days prior to the first dose; or had received antitumor treatment (including herbal medicine with anti-tumor indications) within 28 days prior to the initial dose of the study drug;
- •Not yet adequate recovery from toxicity and / or complications due to any intervention (i. e., grade 1 or at baseline, excluding fatigue or alopecia);
- •Known to of symptomatic CNS metastases and / or cancerous meningitis. The previously treated subjects could participate in the trial if stable (no evidence of radiographic progression within at least 4 weeks before the first dose of trial treatment), repeat imaging confirmed no evidence of new brain metastases or enlargement of lesions, and no steroid treatment was required at least 14 days before the first dose. This exception does not include cancerous meningitis, which should be ruled out regardless of its stable clinical status;
- •Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation;
- •The following laboratory parameters are abnormal:
- •Serum phosphates> ULN;
- •Serum calcium exceeds the normal range, or when serum albumin is beyond the normal range, the corrected calcium concentration of serum albumin is beyond the normal range;
- •Potassium level <lower normal; potassium level can be corrected by supplements at screening.
- •Known history of human immunodeficiency virus (HIV) infection or confirmed positive immune test results;
- •Severe infection with active period or poor clinical control;
- •Thorachydrate, ascites or pericardial effusion with obvious clinical symptoms and requiring drainage;
- •Patients infected with acute or chronic active hepatitis B or hepatitis C, hepatitis B virus (HBV) DNA> 2000 IU / ml or 104Copy / ml; hepatitis C virus (HCV) RNA> 103Copy / ml; hepatitis B surface antigen (HbsAg) was positive with anti-HCV antibody. After the nucleotide antiviral treatment is lower than the above standards, they can be enrolled;
- •Clinically significant or uncontrolled cardiac disease, including unstable angina, acute myocardial infarction within 6 months before the first dose, New York Heart Association grade III / IV congestive heart failure, and uncontrolled cardiac disorders (allowing pacemaker wear or subjects with atrial fibrillation with good heart rate control);
- •With ECG change or medical history considered clinically significant by the investigator; screen QTcF interval> 480 ms, for subjects with indoor block (QRS interval> 120 ms), use JTc interval instead of QTc interval (if JTc is used instead of QTc, JTc must be 340 ms);
- •Uncontrolled hypertension, systolic blood pressure> 160 mmHg or diastolic blood pressure> 100 mmHg after optimal medical treatment, a history of hypertensive crisis or hypertensive encephalopathy;
- •Main exclusion criteria:
- •Other malignant diseases other than digestive tract tumors diagnosed within 5 years before the first dose (excluding radical skin basal cell carcinoma, skin squamous epithelial carcinoma, and / or radical resection);
- •Previous selective FGFR inhibitor therapy;
- •Have received any other study drug or attended an interventional clinical investigator within 28 days prior to the first dose; or had received antitumor treatment (including herbal medicine with anti-tumor indications) within 28 days prior to the initial dose of the study drug;
- •Not yet adequate recovery from toxicity and / or complications due to any intervention (i. e., grade 1 or at baseline, excluding fatigue or alopecia);
- •Known to of symptomatic CNS metastases and / or cancerous meningitis. The previously treated subjects could participate in the trial if stable (no evidence of radiographic progression within at least 4 weeks before the first dose of trial treatment), repeat imaging confirmed no evidence of new brain metastases or enlargement of lesions, and no steroid treatment was required at least 14 days before the first dose. This exception does not include cancerous meningitis, which should be ruled out regardless of its stable clinical status;
- •Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation;
- •The following laboratory parameters are abnormal:
- •Serum phosphates> ULN;
- •Serum calcium exceeds the normal range, or when serum albumin is beyond the normal range, the corrected calcium concentration of serum albumin is beyond the normal range;
- •Potassium level <lower normal; potassium level can be corrected by supplements at screening.
- •Known history of human immunodeficiency virus (HIV) infection or confirmed positive immune test results;
- 另有 18 项未显示
研究组 & 干预措施
experimental group
Experimental
干预措施: Pemigatinib (Drug)
结局指标
主要结局
PFS
时间窗: 6-month PFS
to evaluate the efficacy of pemitinib in patients with advanced gastric cancer who have previously failed standard therapy with FGFR1-3 variants
次要结局
未报告次要终点
研究者
Dong sheng Zhang
chief physician
Sun Yat-sen University
研究点 (1)
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