CTRI/2017/05/008587已完成1 期
A Phase 1b, Multi-center, Study of METREXASSISTTM (Parenteral TK-112690) Administered in Combination with Methotrexate as a Weekly Infusion to Subjects with SCCHN Undergoing Treatment with Methotrexate. A Dose Escalation/Safety study with No Control
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Tosk Inc
- 入组人数
- 25
- 试验地点
- 6
- 主要终点
- DLTs: Any grade 3 or 4 dose-limiting systemic toxicity during the study graded according to the CTCAE (NCI Common Terminology Criteria for Adverse Events), v 4.0 that cannot clearly be attributed to a cause other than TK-112690
研究概览
简要总结
Review of a patient’s medical history including a detailed history of the patient’s cancer and concomitant medications will be performed at screening.
· A screen for drugs of abuse and alcohol will be performed at screening and Day 0 (day before start of study).
· Vital sign measurements at screening, on Day 0, and at 24 and 48 hours post each initial infusion of TK-112690 as well as on Day 1 of Week 5 and 8.
· Physical examinations will be performed at screening, on Day 0, and 24 and 48 hours post each initial infusion of TK-112690 as well as on Day 1 of Week 5 and 8.
· ECOG performance status will be determined at Screening, on Day 0 and at Day 1 of Week 5 and 8.
· For pre-menopausal females, urine pregnancy test at screening, on Day 0 and at Day 1 of Week 5 and 8.
- 12-Lead ECG at screening and 24 hours post each initial infusion of TK-112690
- Serum chemistry, hematology, coagulation and urinalysis at Day 0 and at 24 and 48 hours post each initial infusion of TK-112690 as well as on Day 1 of Week 5 and 8.
- Adverse events will be evaluated 5, 24 and 48 hours post each initial infusion of TK-112690 formulation as well as on Day 1 of Week 5 and 8.
- Blood samples will be obtained pre initial infusion of TK-112690 and 5 and 24 hours post each initial infusion of TK-112690. Plasma will be obtained from the blood samples and analyzed for TK-112690.
- Blood samples will be obtained pre initial infusion of TK-112690 and 5 and 24 hours post each initial infusion of TK-112690. Plasma will be obtained from the blood samples and analyzed for uridine, a biomarker of TK-112690 activity.
- Blood samples will be obtained pre initial infusion of TK-112690 and 5, 24 and 48 hours post each initial infusion as well as on Day 1 of Week 5 and 8. Plasma will be obtained from the blood samples and analyzed for markers indicative of mucositis, eg, CD40/CD40L.
- Mucositis will be evaluated for extent and severity of mucositis using established mucositis rating scales, eg, OMAS/Sonis, PROMS, WHO and CTCAE/mucositis on the day prior to study start (Day 0), and 5, 24 and 48 hours post each initial infusion of TK-112690 or TK-112690 formulation as well as on Day 1 of Week 5 and 8. Examination will assess the lining of the mouth, throat or other linings of the digestive tract. Incidence of oral mucositis, duration of severe oral mucositis, throat soreness, severity of pain and use of parenteral or transdermal opioid analgesics will be assessed.
研究设计
- 研究类型
- Interventional
- 分配方式
- Not Applicable
- 盲法
- Open Label
入排标准
- 年龄范围
- 18.00 Year(s) 至 80.00 Year(s)（—）
- 性别
- All
入选标准
- •â€¢Male and female subjects over 18 years old with a histologically or cytologically confirmed diagnosis of locally advanced, recurrent or metastatic SCCHN, any stage of disease.
- •â€¢No prior systemic treatments for cancer (chemotherapy and/or radiotherapy) 4 weeks prior to screening.
- •â€¢No other concurrent, active, invasive malignancies.
- •â€¢An Eastern Cooperative Oncology Group (ECOG) performance status 0 to
- •â€¢History of brain metastases allowed if disease has stabilized or improved after radiation and/or craniotomy.
- •â€¢No active angina or uncontrolled arrhythmia.
- •â€¢No detectable infection including hepatitis B/C and HIV.
- •â€¢No other concurrent, active, invasive malignancies •Not pregnant or nursing.
- •Women of childbearing potential must have a negative urine pregnancy test at screening and on the day before dosing and must use medically acceptable methods of birth control.
- •Acceptable methods of birth control include oral or transdermal contraceptives, condoms, spermicidal foam, IUD, progestin implant or injection, abstinence, vaginal ring, or sterilization of partner.
- •The reason for non-childbearing potential, such as bilateral tubal ligation, bilateral oophorectomy, hysterectomy, or post-menopausal for ≥ 1 year, must be specified on the patient’s medical history file and CRF.
- •â€¢Must have adequate organ and immune function as indicated by the following laboratory values: Parameter Laboratory Values Serum creatinine£1.5 x ULN Estimated creatinine clearance³45 mL/min Total bilirubin£2.0 mg/dL (£34.2 mmol/L) AST & ALT £3 x ULN Absolute granulocytes³1.5 x 109 cells/L Platelets ³ 100,000/µL •Be able to read, understand, and willing to sign the Informed Consent Form (ICF) before entering the study.
排除标准
- •â€¢Uncontrolled active infection.
- •â€¢Current mucositis (>Grade 1).
- •â€¢Pregnancy or nursing mother.
- •â€¢Prior history of a cerebrovascular accident or hemorrhage.
- •â€¢Congestive heart failure as defined by New York Heart Association class III or IV.
- •â€¢Uncontrolled hypertension.
- •â€¢Active psychiatric/mental illness making informed consent or useful clinical follow-up unlikely.
- •â€¢Subjects who have previously been enrolled into this study and subsequently withdrew.
- •â€¢Subject receiving another investigational agent(s).
- •â€¢Any systemic immunosuppressive medication/therapy (e.g., other chemotherapy, steroids).
- •â€¢Any significant systemic illness, unstable or severe medical condition(s) that could put the subject at risk during the study, interfere with outcome measures or affect compliance with the protocol procedures such as intercurrent infection and/or autoimmune disease, i.e., any condition that compromises the immune system.
- •â€¢Known or suspected intolerance or hypersensitivity to the study materials (TK-112690 and/or excipients or closely related compounds).
- •â€¢Subjects, who have received, or plan to receive, radiation or chemotherapy within 4 weeks of screening.
- •â€¢Subjects that have a history of poor compliance in clinical research studies.
- •â€¢Subjects who have participated in any other investigative clinical trial in the past 4 weeks.
结局指标
主要结局
DLTs: Any grade 3 or 4 dose-limiting systemic toxicity during the study graded according to the CTCAE (NCI Common Terminology Criteria for Adverse Events), v 4.0 that cannot clearly be attributed to a cause other than TK-112690
时间窗: 24 hrs,48 hrs of 1 to 4 week and week 5 and week 8 for Mucositiis Assessment
次要结局
- MTD. Highest dose administered that is not associated with a DLT if three patients are treated or two or more DLTs if 6 patients are treated.(PK. Confirmation that the PK of TK-112690 in patients is similar to the PK profile in healthy volunteers based on WinNonlin analysis of drug plasma concentrations.)
研究者
研究点 (6)
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