NCT03141034已完成2 期
Ramucirumab Plus Irinotecan in Patients With Previously Treated Advanced Gastric or Gastro-esophageal Junction Adenocarcinoma
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 4
- 主要终点
- Progression-free Survival (PFS)
研究概览
简要总结
The investigators hypothesize that this combination regimen of irinotecan plus ramucirumab administered as second line treatment will be tolerated and lead to improved outcomes similar to paclitaxel plus ramucirumab in patients with advanced gastric and gastro-esophageal junction (GEJ) cancers. This study proposes a phase II clinical trial with irinotecan plus ramucirumab for treatment of patients with metastatic gastric and GEJ adenocarcinoma who have progressed after first line chemotherapy. To the knowledge of the investigators, this regimen has not been previously administered to this patient population, so safety and tolerability will be monitored and reported.
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
- •Histopathologically or cytologically confirmed diagnosis of gastric or gastroesophageal junction (GEJ) adenocarcinoma that is metastatic or locally advanced and unresectable.
- •Measurable disease defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 10 mm with CT scan (or MRI at the discretion of the principal investigator (PI)), as ≥ 20 mm by chest x-ray, or ≥ 10 mm with calipers by clinical exam.
- •Either primary or non-osseous metastatic site amenable for research biopsy for patients enrolled at Washington University, if safe and feasible, as confirmed by scheduling of biopsy procedure. Other methods to obtain appropriate cancer cells such as large-volume paracentesis or thoracentesis can be allowed at PI discretion. Biopsy or other procedures should be performed at least 7 days prior to C1D
- •Experienced documented objective radiographic or clinical disease progression during first-line therapy or within 4 months after the last dose of first-line therapy with any platinum/fluoropyrimidine doublet with or without anthracycline (epirubicin or doxorubicin) or taxane (docetaxel) for unresectable or metastatic disease.
- •NOTE: This is not intended to be an exclusive list of allowed agents. The targeted therapies such as Herceptin and ADC, or immunotherapies without cytotoxic chemotherapy, are permitted.
- •At least 18 years of age.
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
- •Normal bone marrow and organ function as defined below:
- •Absolute neutrophil count (ANC) ≥ 1,500/µL
- •Hemoglobin ≥ 9.0 g/dL (5.58 mmol/L)
- •Platelets ≥ 100,000/µL
- •Total bilirubin ≤ 1.5 mg/dL (25.65 µmol/L)
- •AST(SGOT)/ALT(SGPT) ≤ 3.0 x institutional upper limit of normal (IULN) (or ≤ 5.0 x IULN in the setting of liver metastases)
- •Creatinine ≤ 1.5 x IULN OR creatinine clearance ≥ 40 mL/min/1.73 m2 for patients with creatinine levels > 1.5 x IULN (that is, if serum creatinine is > 1.5 x IULN, a 24-hour urine collection to calculate creatinine clearance must be performed)
- •Urinary protein ≤ 1+ on dipstick or routine urinalysis (UA); if dipstick or routine UA is ≥ 2+, a 24-hour urine collection for protein must demonstrate < 1000 mg of protein in 24 hours
- •Adequate coagulation function as defined by INR ≤ 1.5 and PTT ≤ 5 seconds above the ULN (unless receiving anticoagulation therapy). Patients receiving warfarin must be switched to low molecular weight heparin and have achieved stable coagulation profile prior to first dose of protocol therapy.
- •All clinically significant toxic effects (except peripheral neuropathy) of prior locoregional therapy, surgery, or other anticancer therapy have resolved to ≤ Common Terminology Criteria for Adverse Events (CTCAE) grade
- •Women of childbearing potential and men must agree to use two forms of adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately. Women of childbearing potential must have a negative serum pregnancy test within 7 days of study entry.
- •Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).
排除标准
- •Squamous cell or undifferentiated gastric cancer.
- •Received any chemotherapy (including irinotecan) other than platinum and fluoropyrimidine with or without anthracycline or taxane for advanced gastric or GEJ adenocarcinoma.
- •Received previous systemic chemotherapy with a cumulative dose of > 900 mg/m^2 of epirubicin or > 400 mg/m^2 of doxorubicin.
- •Received any previously systemic therapy (including investigational agents) targeting VEGF or the VEGFR signaling pathways. Other previous targeted therapies are permitted if stopped at least 28 days prior to start of treatment.
- •A history of other malignancy ≤ 3 years previous with the exception of basal cell or squamous cell carcinoma of the skin which were treated with local resection only or carcinoma in situ of the cervix or other solid tumors treated curatively and without evidence of recurrence.
- •Currently receiving any other investigational agents.
- •History or evidence of known brain metastases or carcinomatous meningitis. Patients with known brain metastases must be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
- •A history of allergic reactions attributed to compounds of similar chemical or biologic composition to monoclonal antibody treatment, any components used in the ramucirumab DP preparation, irinotecan, or other agents used in the study.
- •Any grade 3-4 GI bleeding within 3 months prior to enrollment.
- •History of gastrointestinal perforation and/or fistulae within 6 months prior to enrollment.
- •History of deep vein thrombosis, pulmonary embolism, or any other significant thromboembolism (venous port of catheter thrombosis or superficial venous thrombosis are not considered "significant") during the 3 months prior to enrollment.
- •History of any arterial thromboembolic event, including but not limited to myocardial infarction, transient ischemic attack, cerebrovascular accident, or unstable angina within 6 months prior to enrollment.
- •Diagnosis of symptomatic congestive heart failure (NYHA II-IV) or symptomatic or poorly controlled cardiac arrhythmia.
- •Uncontrolled or poorly controlled hypertension (> 160 mmHg systolic or > 100 mmHg diastolic for > 4 weeks) despite standard medical management.
- •Presence of serious or nonhealing wound, ulcer, or bone fracture within 28 days prior to enrollment.
- •Major surgery within 28 days prior to first dose of protocol therapy.
- •Minor surgery/subcutaneous venous access device placement within 7 days prior to first dose of protocol therapy.
- •Receiving chronic antiplatelet therapy, including aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs, including ibuprofen, naproxen, and others), dipyridamole or clopidogrel, or similar agents. Once-daily aspirin use (maximum dose 325 mg/day) is permitted.
- •The patient has elective or planned major surgery to be performed during the course of the clinical trial.
- •Bowel obstruction, history or presence of inflammatory enteropathy or extensive intestinal resection (hemicolectomy or extensive small intestine resection with chronic diarrhea), Crohn's disease, ulcerative colitis, or chronic diarrhea.
- •Cirrhosis at a level of Child-Pugh B (or worse) or cirrhosis (any degree) and a history of hepatic encephalopathy or clinically meaningful ascites resulting from cirrhosis (i.e. ascites from cirrhosis requiring diuretics or paracentesis). Patients with ascites not related to cirrhosis, such as malignant ascites, are allowed.
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, metabolic disorders or other nonmalignant organ or systemic disease or secondary effects of cancer that induce a high medical risk and make assessment of survival uncertain, or psychiatric illness/social situations that would limit compliance with study requirements.
- •Pregnant and/or breastfeeding.
- •Known HIV-positivity on combination antiretroviral therapy because of the potential for pharmacokinetic interactions with ramucirumab and irinotecan. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.
研究组 & 干预措施
Irinotecan plus ramucirumab
Experimental
-Patients will receive ramucirumab intravenously on an outpatient basis at a dose of 8 mg/kg over the course of 60 minutes on Day 1 of each 14-day cycle. They will then receive irinotecan intravenously at a dose of 180 mg/m2 over the course of 90 minutes on Day 1 of each 14-day cycle.
干预措施: Irinotecan (Drug)
Irinotecan plus ramucirumab
Experimental
-Patients will receive ramucirumab intravenously on an outpatient basis at a dose of 8 mg/kg over the course of 60 minutes on Day 1 of each 14-day cycle. They will then receive irinotecan intravenously at a dose of 180 mg/m2 over the course of 90 minutes on Day 1 of each 14-day cycle.
干预措施: Ramucirumab (Drug)
Irinotecan plus ramucirumab
Experimental
-Patients will receive ramucirumab intravenously on an outpatient basis at a dose of 8 mg/kg over the course of 60 minutes on Day 1 of each 14-day cycle. They will then receive irinotecan intravenously at a dose of 180 mg/m2 over the course of 90 minutes on Day 1 of each 14-day cycle.
干预措施: Blood for angiome profiling (Genetic)
Irinotecan plus ramucirumab
Experimental
-Patients will receive ramucirumab intravenously on an outpatient basis at a dose of 8 mg/kg over the course of 60 minutes on Day 1 of each 14-day cycle. They will then receive irinotecan intravenously at a dose of 180 mg/m2 over the course of 90 minutes on Day 1 of each 14-day cycle.
干预措施: Blood for cfDNA (Genetic)
结局指标
主要结局
Progression-free Survival (PFS)
时间窗: Up to 30 months from completion of treatment (up to 36 months)
-PFS will be measured from date of study entry to first radiographic progression or death due to any cause. Radiographic progressive disease (PD) will be defined using Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1). For those who are alive and do not experience progression, the investigators will censor them at the time of loss to follow-up or at 30 months from the study entry, whichever comes first.
次要结局
- Overall Survival (OS)(Up to 30 months from completion of treatment (estimated to be 36 months))
- Time to Progressive Disease (TTP)(Up to 30 months from completion of treatment (estimated to be 36 months))
- Objective Response Rate (ORR)(Up to end of treatment (estimated to be 6 months))
- Best Overall Response (BOR)(Up to end of treatment (estimated to be 6 months))
- Clinical Benefit Rate (CBR)(Up to end of treatment (estimated to be 6 months))
- Toxicity and Tolerability of Regimen as Measured by the Count of the Worst Grade of Adverse Event Experienced by Each Participant(Up to 30 days following completion of treatment (median length of follow-up 131.5 days, full range 15-687 days))
研究者
研究点 (4)
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