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 administered daily to Patients scheduled to receive radiotherapy for non-metastatic squamous cell carcinoma of the head and neck (SCCHN).
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Tosk Inc
- 入组人数
- 24
- 试验地点
- 6
- 主要终点
- Primary efficacy outcome measures will be SOM (Comparison of incidences of Grade 3 or 4 WHO mucositis scale in the treatment and placebo groups), and duration of SOM (Days patients suffer Grades 3 and 4 oral mucositis measured by WHO scale during the 7-week treatment period from the start of treatment. Duration is calculated from the day when an oral mucositis score of Grade 2 is reported to onset of a Grade 3 or 4 oral mucositis. Patients with a final grade 0-2 mucositis have a duration of 0).
研究概览
简要总结
All SCCHN patients receive radiation for their disease and most of these suffer mucositis. Only palliative and ineffective treatments like ice chips, sodium bicarbonate chlorhexidine gluconate are available currently to mitigate the condition.
TK-90 for parenteral use, is a novel, non-toxic and specific therapy to prevent and treat mucositis, a major side effect of radiation treatment.
This study is designed primarily to establish, in a placebo- controlled trial, pilot efficacy compared to placebo, and secondarily to confirm the safety and tolerability of TK-90 when administered weekly for 7 weeks to patients with non-metastatic SCCHN. Success will justify exploration of use of TK-90 with other cytotoxics besides MTX and radiation therapy as well other treatments that are known to cause mucositis.
The protocol is designed to explore the anti-mucositis efficacy, tolerability, and safety of TK-90 administered daily along with their radiation treatment as an intravenous infusion in patients with non- metastatic SCCHN. The study will be partially blinded and multicenter. Relevant mucositis, tolerability, and safety endpoints will be collected in the study. Half of the patients will be given 45 mg/kg TK-90 and half will be given TK-90 placebo. All patients will be radiated. Patients at least 18-75 years old, diagnosed with non-metastatic SCCHN and scheduled to receive continuous course of radiation (e.g: 2DRT, 3DRT, IMRT etc.) as single daily fractions of 2.0 Gy, with a cumulative radiation dose of 70 Gy. The diagnosis must be confirmed by histopathology or cytology.
Study treatments: a) Patients will be treated for 5 consecutive days with a 2 Gy radiation treatment followed by a two-day treatment holiday. b) Prior to each radiation treatment the patients will a one-hour infusion of TK-90 (45 mg/kg) or equivalent TK-90 placebo. c) 6 Hours after the end 0f the TK-90 or TK-90 placebo dose, the patients will receive another identical TK-90 or TK-90 placebo treatment. 4) This treatment cycle will continue for 7 weeks. 5) The day before the first treatment, the patients will receive a TK-90 or TK-90 placebo administered 18 and 12 hours before the scheduled radiation treatment.
Follow-up will occur after2 weeks of completion of last dose of radiation or early termination through up to 4 weeks.. Standard safety and anti-mucositis evaluations will occur weekly during treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Participant, Investigator and Outcome Assessor Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 75.00 Year(s)（—）
- 性别
- All
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, oropharynx or hypopharynx.
- •Patients must have at least 1 mucosal site of the oral cavity/oropharynx/hypopharnyx 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/hypopharnyx mucosa 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: i) History/physical examination, including documentation of tobacco/alcohol use and current medications (including opioids/dosing), within 8 weeks prior to randomization. ii) Chest CT scan within 8 weeks prior to randomization. iii) MRI or CT scan with contrast of tumor site within 8 weeks prior to randomization
- •Mucositis Grade less than or equal to 1 per WHO Scale and Xerostomia of Grade less than or equal to 2 per CTCAE version 5.0
- •ECOG Performance Status less than or equal to
- •Adequate bone marrow function as per CTCAE V5, defined as follows (within 2 weeks prior to randomization): i) Absolute neutrophil count more than or equal to 1500cells/mm3 based upon CBC/differential obtained within 2 weeks prior to randomization. ii) Platelets more than or equal to 100,000 cells/mm3 based upon CBC/differential obtained within 2 weeks prior to randomization. iii) Hemoglobin more than or equal to 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 more than 8.0 g/dl is acceptable).
- •Adequate hepatic function with bilirubin less than or equal to 1.5 x upper-normal limit (ULN), AST or ALT less than or equal 3 x ULN within 2 weeks prior to randomization.
- •Adequate renal function with serum creatinine less than 1.5 mg/dl and creatinine clearance (CrC) more than or equal 50 ml/min determined by 24 hour collection or estimated by Cockcroft Gault formula. CrC male is equal to [(
- •age) x (wt in kg)] / [(Serum Cr mg/dl) x (72)]. CrC female is equal to 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) is equal to (4 Patients albumin (g/dl) x 0.8) plus Patients 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: i) Symptomatic and/or uncontrolled cardiac disease, New York Heart Association Classification III or IV.
- •ii) Transmural myocardial infarction within the last 6 months.
- •iii) Acute bacterial or fungal infection requiring intravenous antibiotics at the time of screening.
- •iv) Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of screening.
- •vi) 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.
- •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 patients 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.
结局指标
主要结局
Primary efficacy outcome measures will be SOM (Comparison of incidences of Grade 3 or 4 WHO mucositis scale in the treatment and placebo groups), and duration of SOM (Days patients suffer Grades 3 and 4 oral mucositis measured by WHO scale during the 7-week treatment period from the start of treatment. Duration is calculated from the day when an oral mucositis score of Grade 2 is reported to onset of a Grade 3 or 4 oral mucositis. Patients with a final grade 0-2 mucositis have a duration of 0).
时间窗: Week 1 to Week 7
次要结局
- Secondary efficacy/outcome measures will be mucositis status in the patients evaluated using two different published and validated mucositis scales: NCI/CTCAE/mucositis, and PROMS. Also, comparison of WHO scale values of treated at each point of evaluation.(Plasma concentrations of surrogate markers of mucositis, e.g., citrulline, CD40/CD40L, IL-1β, etc.)