A Phase 2a, Multi-center, Placebo-controlled, Randomized Partially Blinded, Study of Infused METREXASSISTâ„¢ (Parenteral TK-112690) or Metrexassistâ„¢ Placebo Administered Along with Methotrexate Weekly for Four Consecutive Weeks to Patients with Recurrent or Residual SCCHN.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- TOSK INC
- 入组人数
- 22
- 试验地点
- 3
- 主要终点
- Determine pilot efficacy of an iv infusion of TK-112690 to placebo as a mucositis preventive in subjects with locally advanced, residual, orrecurrent or metastatic SCCHN scheduled to receive MTX as chemotherapy.
研究概览
简要总结
A review of a patient’s medical history including a detailed history of the patient’s cancer and concomitant medications will be performed at screening.
Screening for drugs of abuse will be performed at the time of patient screening and Day 0 (the day before start of study).
Vital sign measurements will be performed at patient screening, on Day 0, and at 24 and 48 hours post each initial infusion of TK-112690/placebo as well as on Day 1 of Week 6.
Physical examinations will be performed at screening, on Day 0, and 24 and 48 hours post each initial infusion of TK-112690/ placebo as well as on Day 1 of Week 6.
ECOG performance status will be determined at patient screening, on Day 0, and at Day 1 of Weeks 6.
For pre-menopausal females, a urine pregnancy test will be performed at screening, on Day 0, and at Day 1 of Week 6.
12-Lead ECG at screening and 24 hours post each initial infusion of TK-112690/ Placebo.
CBC, Liver function test, Kidney function test determination at the clinical site prior to methotrexate treatment to ensure patient fitto dose.
Serum chemistry, hematology, coagulation and urinalysis at screening, Day 0, and at 24 and 48 hours post each initial infusion of TK-112690/ placebo as well as on Day 1 of Week 6.
Adverse events will be evaluated 5, 24 and 48 hours post each initial infusion of TK-112690/ Placebo as well as on Day 1 of Week 6.
Blood samples will be obtained pre-initial infusion of TK-112690/ placebo and 5, 24 and 48 hours post each initial infusion as well as on Day 1 of Week 6. Plasma will be obtained from the blood samples in order to determine surrogate markers of mucositis, e.g., CD40/CD40L, TNF-α, etc.
Patients will be evaluated for extent and severity of mucositis using established mucositis rating scales, e.g., OMAS/Sonis, PROMS, WHO, and CTCAE/mucositis on the day prior to study start (Day 0), and 24 and 48 hours post each initial infusion of TK-112690/ placebo as well as on Day 1 of Week 6. Examination will assess the lining of the mouth, throat, and 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
- Computer generated randomization
入排标准
- 年龄范围
- 18.00 Year(s) 至 70.00 Year(s)（—）
- 性别
- All
入选标准
- •Male and female subjects over 18 years old with a histologically or cytological confirmed diagnosis of locally residual, recurrent or metastatic SCCHN.
- •Subject must have failed at least onecourses of non-MTX chemotherapy, orone course of non-MTX chemotherapyand chemo radiation for treating their SCCHN.
- •No prior systemic treatments for cancer (chemotherapy and/or radiotherapy) 4 weeks prior to screening.
- •No other concurrent, active, invasive malignancies.
- •An Eastern Cooperative Oncology Group (ECOG) performance status of 0 to
- •History of brain metastases allowed if disease has stabilized or improved after radiation and/or craniotomy.
- •No active angina or uncontrolled arrhythmia.
- •No detectable infection including hepatitis B/C and HIV.
- •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 in the patient’s medical history file and CRF.
- •Must have adequate organ and immune function as indicated by the following laboratory values: Parameter Laboratory Values Serum creatinine ≤1.5 x ULN Est.
- •creatinine clearance ≥45 mL/min Total bilirubin≤2.0 mg/dL (≤34.2 μmol/L) AST & ALT ≤3 x ULN Absolute granulocytes ≥1.5 x 109 cells/L Platelets ≥100,000/µL Be able to read orunderstand, and provide a signature or thumb impression on the Informed Consent Form (ICF) before entering the study.
排除标准
- •Subject has not failed at least onecourses of non-MTX chemotherapyor one course of non-MTX chemotherapy and chemo radiation for treating their SCCHN.
- •Uncontrolled active infection.
- •Current mucositis (>Grade 1).
- •Pregnant or nursing mother.
- •Prior history of a cerebrovascular accident or hemorrhage.
- •Congestive heart failure, as defined by New York Heart Association class III or IV.
- •Uncontrolled hypertension.
- •Active psychiatric/mental illness making informed consent or useful clinical follow-up unlikely.
- •Subjects who have previously been enrolled into this study and subsequently withdrew.
- •Subject receiving other investigational agent(s).
- •Any systemic immunosuppressive medication/therapy (eg, other chemotherapy, steroids).
- •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, ie, any condition that compromises the immune system.
- •Known or suspected intolerance or hypersensitivity to the study materials (TK-112690 and/or excipients or closely related compounds).
- •Subjects, who have received, or plan to receive, radiation or chemotherapy within 4 weeks of screening.
- •Subjects that have a history of poor compliance in clinical research studies.
结局指标
主要结局
Determine pilot efficacy of an iv infusion of TK-112690 to placebo as a mucositis preventive in subjects with locally advanced, residual, orrecurrent or metastatic SCCHN scheduled to receive MTX as chemotherapy.
时间窗: Patients will be evaluated for extent and severity of mucositis using established mucositis rating | scales, e.g., OMAS/Sonis, PROMS, WHO, and CTCAE/mucositis on the day prior to study start | (Day 0), and 24 and 48 hours post each initial infusion of TK-112690/ placebo as well as on | Day 1 of Week 6.
次要结局
- Confirmation of the safety/tolerability of a continuous administered weekly for 4 weeks and lowering of plasma concentrations of surrogate markers of mucositis, e.g., CD40/CD40L, post TK-112690 in patients suffering from local, advanced, residual or recurrent, metastatic SCCHN receiving sequential continuous iv infusions of TK-112690 and MTX or TK-112690 placebo and MTX.(Predose and postdose 24 hr and 28 hr safety samples for 4 week.6 week safety sample.also surrgoate Biomarkers at every week .)