NCT03775525进行中（未招募）1 期
A Phase I/Ib, Multicenter, Open-label, Dose-Escalation, Safety, Pharmacodynamic and Pharmacokinetic Study of GZ17-6.02 Monotherapy and in Combination With Capecitabine, Given Orally on a Daily Schedule in Patients With Advanced Solid Tumors or Lymphoma
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 127
- 试验地点
- 4
- 主要终点
- maximum tolerated dose (MTD)
研究概览
简要总结
This Phase I/Ib study is a Multicenter, Open-label, Dose-Escalation, Safety, Pharmacodynamic and Pharmacokinetic Study of GZ17-6.02 Monotherapy and in Combination with Capecitabine, Given Orally on a Daily Schedule in Patients with Advanced Solid Tumors or Lymphoma
详细描述
This study will evaluate the safety, pharmacokinetics, and pharmacodynamic effects of a novel anti-cancer drug, GZ17-6.02 administered to patients with advanced solid tumors or lymphoma, which have progressed after receiving standard/approved therapy or where there is no approved therapy.
This study will determine the maximum tolerated dose (MTD) and the dose limiting toxicities (DLT) of GZ17-6.02 monotherapy and in combination with standard-of-care oncology treatments and to establish the dose of GZ17-6.02 recommended for future monotherapy and combination therapies phase II oncology clinical studies.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Patients with a pathologically confirmed diagnosis of advanced solid tumors or lymphoma.
- •Tumor progression after receiving standard/approved therapies which may include chemotherapy, targeted agents, radio-immuno conjugates, check point inhibitors, where there is no approved therapy; or the patient is intolerant of standard of care or the patient declines standard of care treatment
- •One or more metastatic tumors measurable, or evaluable, per RECIST v1.1 Criteria for solid tumors and Lugano Criteria for lymphoma
- •Have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1
- •Life expectancy of at least 3 months
- •Age 18 years
- •Signed, written IRB-approved informed consent
- •A negative pregnancy test (if female)
- •Acceptable liver function:
- •Bilirubin ≤ 1.5 times upper limit of normal
- •AST (SGOT), ALT (SGPT) and Alkaline phosphatase ≤ 2.5 times upper limit of normal (if liver metastases are present, then ≤ 5 x ULN is allowed)
- •Acceptable renal function:
- •o Serum creatinine ≤ 1.5 times institutional ULN, OR calculated creatinine clearance ≥ 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal.
- •Acceptable hematologic status:
- •Granulocyte ≥ 1500 cells/mm3
- •Platelet count ≥ 100,000 (plt/mm3)
- •Hemoglobin ≥ 9 g/dL
- •Urinalysis:
- •o No clinically significant abnormalities
- •Acceptable coagulation status (for patients on warfarin or other anti-coagulants, a PT/PTT considered by the PI as therapeutically appropriate will be allowed):
- •PT within ≤ 1.5 times normal limits
- •PTT within ≤ 1.5 times normal limits
- •For men and women of child-producing potential, the use of effective contraceptive methods during the study
- •Fasting glucose ≤ 180 mg/dL
- •Albumin ≥ 3.0 g/dL within seven days of initiating protocol treatment
- •For patients in the GZ17-6.02 plus capecitabine Phase 1b Expansion Cohort 2 (metastatic breast cancer):
- •Pathologically confirmed diagnosis of HER2-negative and Hormone Receptor (HR) (estrogen receptor [ER] and/or progesterone receptor)-positive metastatic breast cancer;
- •Had ≤ 1 prior treatment (not including neoadjuvant or adjuvant treatment);
- •Are naïve to capecitabine but not necessarily to fluorouracil (5 FU);
- •Eligible for standard-of-care treatment with capecitabine monotherapy.
- •Patients in Expansion Cohort 2 with bone-only metastatic disease must have one or more lytic or a mixed lytic-blastic lesions that can be assessed by computed tomography (CT) scan or magnetic resonance imaging (MRI).
- •For patients in GZ17-6.02 plus capecitabine Phase 1b Expansion Cohort 3 (metastatic colorectal cancer):
- •Pathologically confirmed diagnosis of metastatic colorectal cancer;
- •Had ≤ 2 prior treatments (not including neoadjuvant or adjuvant treatment);
- •Are naïve to capecitabine but not necessarily to 5 FU;
- •Eligible for standard-of-care treatment with capecitabine monotherapy.
排除标准
- •(All patients, unless otherwise specified):
- •New York Heart Association Class III or IV, cardiac disease, myocardial infarction within the past 6 months, unstable arrhythmia, or evidence of ischemia on ECG.
- •Currently taking MAOIs
- •Baseline QTc exceeding 450 msec in males, 470 msec in females (using the Fridericia's formula) and/or patients receiving class 1A or class III antiarrhythmic agents;
- •Known active, uncontrolled bacterial, viral, or fungal infections requiring systemic therapy;
- •Pregnant or nursing women.
- •NOTE: Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; or 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 should inform her treating physician immediately.
- •Treatment with radiation therapy or surgery within 1 month prior to study entry.
- •Treatment with chemotherapy, targeted therapeutics (e.g. tyrosine kinase inhibitors, therapeutic antibodies, etc), or investigational therapies within 1 month, or 5 half-lives (whichever is shorter), prior to study entry (6 weeks for nitrosoureas or mitomycin C). For radiopharmaceuticals, within 1 month unless hematopoietic recovery has not returned to pretreatment baseline;
- •Unwillingness or inability to comply with procedures required in this protocol;
- •Known active infection with HIV, HTLV-1, hepatitis B, hepatitis C or other chronic viral infections that could interfere with the interpretation of study data;
- •Serious nonmalignant disease (e.g., hydronephrosis, liver failure, or other conditions) that could compromise protocol objectives in the opinion of the investigator and/or the sponsor.
- •Patients who are currently receiving any other investigational agent;
- •Primary Central Nervous System (CNS) malignancies;
- •Active CNS metastases requiring treatment or radiotherapy, or which have not been confirmed stable on radiographic imaging for ≥30 days prior to C1D1;
- •Patients requiring steroids for neurological signs and symptom stabilization.
- •Patients who are unable to successfully discontinue all prohibited medications listed in Appendix 6;
- •Patients must not have received a transfusion (platelets or red blood cells) ≤ 2 weeks prior to initiating protocol therapy.
- •For patients in the GZ17-6.02 monotherapy Dose Escalation Cohort and patients in Expansion Cohort 1:
- •Patients with cow's milk allergy or with galactosemia
- •Phase 1b Expansion Cohort 2 (metastatic breast cancer) and Expansion Cohort 3 (metastatic colorectal cancer):
- •Any history of coronary artery disease is exclusionary; New York Heart Association Class III or IV, cardiac disease, myocardial infarction within the past 6 months, unstable arrhythmia, or evidence of ischemia on the ECG.
- •Any conditions or medications that are contraindicated with capecitabine dosing;
- •Dihydropyrimidine dehydrogenase (DPD) deficiency;
- •Known sensitivity to capecitabine or any of its components or to 5-FU ;
- •Serious nonmalignant disease (e.g., hydronephrosis, liver failure, or other conditions) that could compromise protocol objectives in the opinion of the investigator and/or the sponsor
- •o This includes prior gastrointestinal surgery that would interfere with the oral drug absorption.
- •Malignancy other than metastatic breast cancer (Expansion Cohort 2) or metastatic colorectal cancer (Expansion Cohort 3) that required therapy within the preceding 5 years, other than adequately treated:
- •non-melanoma skin cancer or in situ cancer;
- •another cancer that has a very low risk of interfering with the safety or efficacy endpoints of the study, must be approved by the Sponsor medical team.
研究组 & 干预措施
Experimental: monotherapy
Experimental
GZ17-6.02 given orally on a daily x 28 day schedule. This will be a dose escalation study.
干预措施: GZ17-6.02 (Drug)
Experimental: Combination with Capecitabine in Metastatic Hormone Receptor Positive Breast Cancer
Experimental
GZ17-6.02 given orally twice daily x 21 day schedule in combination with Capecitabine 825 mg/m2 orally twice daily for 14 days x 21 day schedule.
干预措施: GZ17-6.02 (Drug)
Experimental: Combination with Capecitabine in Metastatic Hormone Receptor Positive Breast Cancer
Experimental
GZ17-6.02 given orally twice daily x 21 day schedule in combination with Capecitabine 825 mg/m2 orally twice daily for 14 days x 21 day schedule.
干预措施: Capecitabine (Drug)
Experimental: Combination with Capecitabine in Metastatic Colorectal Cancer
Experimental
GZ17-6.02 given orally twice daily x 21 day schedule in combination with Capecitabine 850 mg/m2 orally twice daily for 14 days x 21 day schedule.
干预措施: GZ17-6.02 (Drug)
Experimental: Combination with Capecitabine in Metastatic Colorectal Cancer
Experimental
GZ17-6.02 given orally twice daily x 21 day schedule in combination with Capecitabine 850 mg/m2 orally twice daily for 14 days x 21 day schedule.
干预措施: Capecitabine (Drug)
结局指标
主要结局
maximum tolerated dose (MTD)
时间窗: 18 months
As assessed by CTCAE v4.03
Recommended dose of GZ17-6.02 for future phase II clinical studies
时间窗: 18 months
Dose-limiting toxicity
时间窗: 18 months
次要结局
- Antitumor effect(18 months)
- Terminal Phase Half-Life (t1/2)(18 months)
- Area Under Concentration Curve(18 months)
- Maximum Plasma Concentration (Cmax)(18 months)
- Time to Maximum Plasma Concentration (Tmax)(18 months)
- Total Body Clearance (CL/F)(18 months)
- Apparent Volume of Distribution (Vd/F)(18 months)
研究者
研究点 (4)
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