Phase 2, Multi-center, Randomized, Double-blind, Placebo-controlled Study to Evaluate EC-18 for Oral Mucositis in Patients With Concomitant Chemoirradiation for Cancers of the Mouth, Oropharynx, Hypopharynx and Nasopharynx
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 105
- 试验地点
- 19
- 主要终点
- Duration of Severe Oral Mucositis (SOM) during the active treatment and short-term follow-up periods
研究概览
简要总结
This is a Phase 2, randomized, double-blind, placebo-controlled, 2-stage trial in subjects with squamous cell cancers of the mouth, oropharynx, hypopharynx and nasopharynx planned to receive standard fractionated IMRT-delivered radiotherapy with concomitant chemotherapy (cisplatin). Informed consent will be obtained from each subject prior to enrollment.
The trial will be performed in 2 stages:
Stage 1 will consist of a blinded parallel group safety study of 4 cohorts in which 24 subjects will be randomized (1:1:1:1) into four equally sized groups to receive one of three doses of EC-18 (500 mg, 1000 mg, 2000 mg; unit dose of 500 mg) or placebo. Stage 2 of the study will evaluate both safety and efficacy.
Stage 2 will consist of eighty (80) subjects who will be randomized in a 1:1 scheme to receive either placebo or 2000 mg of EC-18 as determined by iDSMB in Stage 1.
详细描述
This is a Phase 2, randomized, double-blind, placebo-controlled, 2-stage trial in subjects with squamous cell cancers of the mouth, oropharynx, hypopharynx and nasopharynx planned to receive standard fractionated IMRT-delivered radiotherapy with concomitant chemotherapy (cisplatin). Informed consent will be obtained from each subject prior to enrollment.
The trial will be performed in 2 stages:
Stage 1 will consist of a blinded parallel group safety study of 4 cohorts in which 24 subjects will be randomized (1:1:1:1) into four equally sized groups to receive one of three doses of EC-18 (500 mg, 1000 mg, 2000 mg; unit dose of 500 mg) or placebo delivered in the following daily schedule:
TDD AM PM Placebo 2 placebo 2 placebo 500mg 1 active + 1 placebo 2 placebo 1000mg 1 active + 1 placebo 1 active + 1 placebo 2000mg 2 active 2 active Dosing will commence on the first day of radiation (one hour after the first fraction) and continue until the last day of radiation. Test drug will be administered as an oral 500 mg capsule in divided daily doses as indicated above. At the completion of 4 weeks of dosing, an independent Data Safety Monitoring Board (DSMB) will evaluate safety endpoints in blinded fashion. If no safety issues are identified, the DSMB will approve continuation of dosing until the last day of radiation. If a safety issue is noted, the DSMB may unblind the treatment assignment to ascertain if the adverse event is associated with study drug. DSMB assessment will be repeated after completion of dosing (when each subject has been dosed through the last day of radiation). If no safety issues are identified, the efficacy component of the study (Stage 2) will commence using the highest dose of study drug consistent with a positive safety outcome.
Stage 2 of the study will evaluate both safety and efficacy. Eighty (80) subjects will be randomized in a 1:1 scheme to receive either placebo or 2000 mg of EC-18 as determined by iDSMB in Stage 1. Twice daily dosing will begin on the first day of radiation (1 hour after the first fraction) and continue until the last day of radiation (approximately 7 weeks).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
Subjects and investigators will be blinded to treatment assignments
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
- •Signed informed consent
- •Male or female age 18 years or older
- •Pathologically confirmed diagnosis of squamous cell carcinoma of the mouth, oropharynx, hypopharynx or nasopharynx
- •Planned to receive IMRT with daily fractions of 2.0 Gy to 2.2 Gy to a cumulative dose of at least 60 Gy and a maximum of 72 Gy
- •Radiation fields to include at least two mucositis sites at risk (buccal mucosa, floor of mouth, ventral and lateral tongue, soft palate) in which both sites receive a minimum cumulative dose of 55 Gy
- •Planned to receive concomitant single agent chemotherapy with cisplatin given either weekly or tri-weekly
- •Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1
- •Screening Laboratory Values Hemoglobin ≥ 9g/dL White blood cell count ≥ 3,500 cells/mm3 Absolute neutrophil count ≥ 1,500 cells/mm3 Total bilirubin ≤ 2 times upper limit of normal Serum AST and ALT ≤ 2.5 times upper limit of normal Serum creatinine concentration ≤ 2mg/mL Pregnancy test: negative for females of childbearing potential
- •Subjects of childbearing potential must consent to utilize a medically accepted means of contraception throughout the active dosing period with study medication and for a minimum of 30 days following the administration of the last dose of study medication.
排除标准
- •Unable to provide informed consent or, in the opinion of the Principal Investigator, comply with the protocol.
- •Prior radiation therapy to the head and neck
- •Metastatic disease
- •Presence of active infectious disease excluding oral candidiasis
- •Presence of oral mucositis or any oral lesion that would confound the assessment of oral mucositis
- •Active systemic disease or condition known to impact the risk or course of oral mucositis including chronic immunosuppression and known seropositivity for HIV
- •Use of any investigational agent within 30 days of the first radiation dose
- •Active alcohol abuse syndrome
- •Subjects with a history of hepatitis of any etiology or hepatic insufficiency
- •Pregnant or nursing at the time of signing informed consent
- •Known sensitivity to any study medication
- •Unwilling or unable to complete study diary
- •Any other condition or prior therapy that, in the opinion of the Investigator, would make the subject unsuitable for the study or unable to comply with the protocol
研究组 & 干预措施
[Part 1] Placebo
Matching placebo
干预措施: Placebo (Drug)
[Part 1] EC-18 500 mg
1 capsule of EC-18
干预措施: EC-18 (Drug)
[Part 1] EC-18 1000 mg
2 capsules of EC-18 500 mg
干预措施: EC-18 (Drug)
[Part 1] EC-18 2000 mg
4 capsules of EC-18 500 mg
干预措施: EC-18 (Drug)
[Part 2] Placebo
Placebo 2000mg
干预措施: Placebo (Drug)
[Part 2] EC-18 2000mg
RP2D: EC-18 2000mg (Part 1 result)
干预措施: EC-18 (Drug)
结局指标
主要结局
Duration of Severe Oral Mucositis (SOM) during the active treatment and short-term follow-up periods
时间窗: 7 Weeks (Active) + 4-6 Weeks (STFU)
Duration of Grade 3 or 4 oral mucositis
次要结局
- Incidence of severe oral mucositis defined as WHO grade of 3 or 4 during the active treatment period(7 Weeks (Active))
- Incidence of severe oral mucositis defined as WHO grade of 3 or 4 during the active treatment and short-term follow-up periods(7 Weeks (Active) + 4-6 Weeks (STFU))
- Incidence of ulcerative mucositis (defined as WHO grade of 2, 3, or 4) during the active treatment period(7 Weeks (Active))
- Incidence of ulcerative mucositis (defined as WHO grade of 2, 3, or 4) during the active treatment and short-term follow-up periods(7 Weeks (Active) + 4-6 Weeks (STFU))
- Delay in onset of SOM (WHO criteria)(Start of the radiation treatment (Day 1) until SOM has resolved (up to 22 weeks))
- Reduction in patient-reported mucositis-related mouth pain and analgesic use(7 Weeks (Active) + 4-6 Weeks (STFU))
- Duration of SOM during the active treatment period(7 Weeks (Active))
- Duration of ulcerative mucositis (WHO criteria)(From the onset to the day when ulcerative mucositis has resolved (up to 22 weeks))