A Phase 2a, Multi-center, Placebo-Controlled, Randomized, Assessor-blind Study to Assess the Safety & Efficacy of Parenteral TK-90 or Parenteral TK-90 Placebo to Patients Receiving Radiotherapy for Non-Metastatic Squamous Cell Carcinoma of Head and Neck.
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- Tosk, Inc.
- 入组人数
- 24
- 试验地点
- 5
- 主要终点
- Mucositis
研究概览
简要总结
Patients expected to receive a continuous course of radiation as single daily fractions of 2.0 Gy treatment with a cumulative radiation dose of 70 Gy. The radiation can be 2DRT, 3DRT,IMRT etc. Prior to each radiation treatment the patients will receive a one-hour infusion of TK-90 or equivalent TK-90 placebo depending on randomization. 6 Hours after the completion of TK-90 infusion or TK-90 placebo dose, the patients will receive another identical TK-90 or TK-90 placebo treatment depending on randomization. This treatment cycle will continue for 7 weeks. The TK112690 dose will be 45 mg/kg.
详细描述
Patients expected to receive a continuous course of radiation as single daily fractions of 2.0 Gy treatment with a cumulative radiation dose of 70 Gy. The radiation can be 2DRT, 3DRT,IMRT etc. Prior to each radiation treatment the patients will receive a one-hour infusion of TK-90 or equivalent TK-90 placebo depending on randomization. 6 Hours after the completion of TK-90 infusion or TK-90 placebo dose, the patients will receive another identical TK-90 or TK-90 placebo treatment depending on randomization. This treatment cycle will continue for 7 weeks. The TK112690 dose will be 45 mg/kg.
- 24 patients will be randomized equally into 2 different groups: TK-90 treated or TK-90 placebo treated.
- Screening must be completed within 2 weeks.
- The treatment period for the study is 7 weeks.
- Study follow-up will be scheduled post two weeks of completion of last dose of radiation or early termination through up to 4 weeks.
- Blinding: The study will be partially blinded. The patient and investigator as well as site personnel will be blinded as to whether TK-90 or TK-90 placebo is administered. The CRO, sponsor, and site pharmacist will know whether the patient was administered active drug or TK-90 placebo.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
The study will be partially blinded. The patient and investigator as well as site personnel will be blinded as to whether TK-90 or TK-90 placebo is administered. The CRO, sponsor, and site pharmacist will know whether the patient was administered active drug or TK-90 placebo.
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants must meet ALL of the following criteria at the time of screening unless otherwise specified:
- •Patient must sign study specific informed consent prior to study entry.
- •Male or Female patient aged 18 - 75 years.
- •Pathologically (histologically or cytologically) proven (from primary lesion and/or lymph nodes) diagnosis of squamous cell carcinoma of the oral cavity (Refer Definition in 10.13.1), oropharynx or hypopharynx.
- •Patients must have at least 1 mucosal site of the oral cavity/oropharynx/hypopharynx mucosa assessable by visual transoral inspection that will receive cumulative radiation dose of 70 Gy.
- •Note: Unavoidable doses of at least 60 Gy, to include entrance, exit, and scatter doses, still constitutes planned radiation.
- •Patients with tumors of the larynx or hypopharynx are eligible only if it is anticipated that at least 1 index site in the oral cavity/oropharynx/hypopharynx mucosa (Refer section 10.13.1) will receive cumulative radiation dose of 70 Gy.
- •Selected Stage I to III or IVA-B per AJCC, Cancer Imaging Manual, 8th edition, at study entry, including no distant metastases other than non- metastatic SCCHN, based upon the following minimum diagnostic workup:
- •History/physical examination, including documentation of tobacco/alcohol use and current medications (including opioids/dosing), within 8 weeks prior to randomization.
- •Chest CT scan within 8 weeks prior to randomization.
- •MRI or CT scan with contrast of tumor site within 8 weeks prior to randomization.
- •Mucositis Grade ≤ 1 per WHO Scale and Xerostomia of Grade ≤ 2 per CTCAE version 5.0
- •ECOG Performance Status ≤
- •Adequate bone marrow function as per CTCAE V 5, defined as follows (within 2 weeks prior to randomization):
- •Absolute neutrophil count ≥ 1500cells/mm3 based upon CBC/differential obtained within 2 weeks prior to randomization.
- •Platelets ≥ 100,000 cells/mm3 based upon CBC/differential obtained within 2 weeks prior to randomization.
- •Hemoglobin ≥ 8.0 g/dl based upon CBC/differential obtained within 2 weeks prior to randomization (Note: The use of transfusion or other intervention to achieve Hgb> 8.0 g/dl is acceptable).
- •Adequate hepatic function with bilirubin ≤ 1.5 x upper-normal limit (ULN), AST or ALT ≤3 x ULN within 2 weeks prior to randomization.
- •Adequate renal function with serum creatinine < 1.5 mg/dl and creatinine clearance (CrC) ≥ 50 ml/min determined by 24-hour collection or estimated by Cockcroft-Gault formula. CrC male = [(140 - age) x (wt in kg)] / [(Serum Cr mg/dl) x (72)]. CrC female = 0.85 x (CrCl male) within 2 weeks prior to randomization.
- •Normal serum calcium or normal corrected serum calcium within 2 weeks prior to randomization; formula for corrected calcium if albumin valued is below normal range: Corrected calcium (mg/dl) = (4 - [Patient's albumin (g/dl)] x 0.8) + Patient's measured calcium (mg/dl).
- •Negative serum pregnancy test for women of childbearing potential.
- •Women of childbearing potential and male participants with female partners of childbearing potential must practice adequate contraception.
排除标准
- •Patients who meet any of the following criteria at the time of screening will be excluded:
- •Stage IVC (Any T, Any N, M1) per AJCC Cancer Staging Manual. 8th ed, or distant metastases at protocol study entry other than metastatic SCCHN.
- •Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years.
- •Patients who have not fully recovered after prior surgery. (Patients who have had prior surgery and have fully recovered and patients who may have surgery in the future are eligible.).
- •Severe, active co-morbidity, defined as follows:
- •Symptomatic and/or uncontrolled cardiac disease, New York Heart Association Classification III or IV.
- •Transmural myocardial infarction within the last 6 months.
- •Acute bacterial or fungal infection requiring intravenous antibiotics at the time of screening.
- •Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of screening.
- •Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects.
- •Patients known to be sero-positive for human immunodeficiency virus (HIV), hepatitis B (HBV), hepatitis C (HCV).
- •Collagen vascular disease, such as scleroderma.
- •Previous treatment with palifermin or other keratinocyte growth factors, such as velafermin or repifermin, within 28 days of randomization.
- •Any prohibited therapy 2 weeks prior to randomization (see Section 8.4).
- •Pregnancy, breast feeding or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception.
- •Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results.
- •Known hypersensitivity study medication or excipients in the formulation.
- •Any illness or medical conditions that are unstable or could jeopardize the safety of the patient and his/her compliance in the study.
研究组 & 干预措施
TK112690
TK112690 treatment
干预措施: TK-112690 (Drug)
Placebo
TK112690 formulation
干预措施: Placebo (Drug)
结局指标
主要结局
Mucositis
时间窗: 7 weeks
* SOM (Severe Oral Mucositis) - Comparison of incidences of Grade 3 or 4 mucositis (WHO scale) in the treatment and placebo groups. * Duration of SOM (Severe Oral Mucositis). Days patients suffer Grades 3 and 4 oral mucositis measured by WHO scale from the start of treatment. * Calculate Number of days from the first occurrence of WHO Grade 3 or 4 oral mucositis through the first occurrence of non-severe (≤ Grade 2) without a subsequent instance of ≥ Grade 3 oral mucositis. * Subjects with complete study follow-up for SOM who do not develop severe oral mucositis (grade 0-2) will be considered to have duration of 0 days.
次要结局
- Secondary efficacy/outcome mucositis(7 weeks)
- Incidence Adverse Events That Are Related to Treatment(7 Weeks)