A Phase 2, Multi-center, Randomized, Double-blind, Placebo-controlled Clinical Trial to Evaluate the Safety and Efficacy of ALD518 in the Reduction of Oral Mucositis in Subjects With Head and Neck Cancer Receiving Concomitant Chemotherapy and Radiotherapy
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- CSL Behring
- 入组人数
- 76
- 试验地点
- 31
- 主要终点
- Percent of Participants With Adverse Events, Serious Adverse Events and Clinically Significant Laboratory Abnormalities
研究概览
简要总结
The purpose of this study is to evaluate the safety and efficacy of ALD518 in modifying the course of oral mucositis in subjects with head and neck cancer receiving concomitant chemotherapy and radiotherapy
详细描述
This was a Phase 2, placebo-controlled, double-blind study in subjects newly diagnosed with head and neck cancer (who had not received previous treatment for oral mucositis) and who were receiving concomitant chemotherapy and radiotherapy. Subject eligibility, including tumor staging, was assessed during the screening period, which was to occur within 30 days prior to the initiation of radiation therapy. The radiation therapy treatment period was approximately 7 weeks, depending on the subject's prescribed radiation plan. Prior to the randomized portion of the trial, the first 7 subjects enrolled in the study entered a safety run-in evaluation and received a total of 2 doses of open-label clazakizumab 160 mg IV, 4 weeks apart (Day 0 and Week 4 of radiation); these subjects were not eligible for the randomized portion of the study. Subsequent to completion of the safety run-in, eligible subjects were randomized 1:1:1 to treatment with 2 doses of clazakizumab 160 mg, or clazakizumab 320 mg, or placebo, administered IV 3 weeks apart (Day 0 and Week 3 of radiation therapy). All subjects were to be followed for 4 weeks post last day of radiotherapy treatment for the primary efficacy and safety assessments and then for up to an additional 12 months of long-term follow-up.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Have recently diagnosed (< than 6 months prior to screening visit date), pathologically confirmed, non-metastatic SCC of the oral cavity, oropharynx, hypopharynx or larynx that will be treated with CRT as first-line treatment; subjects with a history of surgical management (approximately 4-6 weeks before RT with sufficient time for post-surgical healing) are eligible
- •Have a plan to receive a continuous course of conventional external beam irradiation delivered by intensity-modulated radiotherapy (IMRT) as single daily fractions of 2.0 to 2.2 Gy, with a cumulative radiation dose between 55 and 72 Gy.
- •Have a plan to receive a standard cisplatin CT regimen administered tri-weekly (80 to 100 mg/m2, on Days 0, 21, and 42) or weekly (30 to 40 mg/m2) or a standard carboplatin regimen administered weekly (100 mg/m2)
- •Have an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
- •CRP < 80 mg/L
- •Have adequate hematopoietic, hepatic, and renal function at the screening visit
排除标准
- •Tumor of the lips, sinuses, salivary glands, nasopharynx or unknown primary tumor
- •Metastatic disease (M1) Stage IV C
- •Any prior history of head and neck cancer
- •Prior radiation to the head and neck
- •Have had a major surgical procedure, other than for HNC, or significant traumatic injury within 4 weeks prior to the initiation of RT; or anticipation of need for a major surgical procedure during the clinical trial
- •Active infectious disease, excluding oral candidiasis
- •Have OM at the screening visit
- •Have a history of hypersensitivity to monoclonal antibody
研究组 & 干预措施
Open Label ALD518
干预措施: ALD518 (Biological)
ALD518 Dose 1
干预措施: ALD518 (Biological)
ALD518 Dose 2
干预措施: ALD518 (Biological)
Placebo
干预措施: 0.9% saline (Drug)
结局指标
主要结局
Percent of Participants With Adverse Events, Serious Adverse Events and Clinically Significant Laboratory Abnormalities
时间窗: Up to 15 months
Number of Participants With Adverse Events, Serious Adverse Events and Clinically Significant Laboratory Abnormalities
时间窗: Up to 15 months
Percent of Participants With All Grades of Oral Mucositis (OM) at a Radiation Dose of 55 Gy
时间窗: Up to 12 weeks
Gray (Gy) is used as a unit of the radiation quantity absorbed dose that measures the energy deposited by ionizing radiation in a unit mass of matter being irradiated, and is used for measuring the delivered dose of ionizing radiation in applications such as radiotherapy. The 55 Gy ulcerative OM assessment is defined as the first ulcerative OM assessment that occurred on the day of or after the subject received the radiation therapy that first resulted in their cumulative dose of radiation being ≥ 55 Gy
Number of Participants With All Grades of OM at a Radiation Dose of 55 Gy
时间窗: Up to 12 weeks
The 55 Gy ulcerative OM assessment is defined as the first ulcerative OM assessment that occurred on the day of or after the subject received the radiation therapy that first resulted in their cumulative dose of radiation being ≥ 55 Gy
次要结局
- Time to Onset of Ulcerative and Severe OM(Up to 12 weeks)
- Percent of Participants With Ulcerative OM at Varying Cumulative Radiation Doses (Gy)(Up to 12 weeks)
- Percent of Participants With Severe OM at Varying Cumulative Radiation Doses (Gy)(Measured from onset of OM through Week 12)
- Number of Participants With Severe OM at Varying Cumulative Radiation Doses (Gy)(Up to 12 weeks)
- Number of Participants With Ulcerative OM at Varying Cumulative Radiation Doses (Gy)(Up to 12 weeks)
- Duration of Ulcerative and Severe OM(Up to 12 weeks)
- ALD518 Plasma Concentration at Varying Weeks(Baseline and up to 12 weeks)
- Functional Assessment of Cancer Therapy - Head and Neck (FACT-HN) Questionnaire Overall Assessment Score at Varying Cumulative Radiation Doses (Gy)(Baseline and up to 12 weeks)
- Functional Assessment of Chronic Illness Therapy - Fatigue Questionnaire (FACIT-F) Score at Varying Cumulative Radiation Doses (Gy)(Baseline and up to 12 weeks)
- Oral Mucositis Daily Questionnaire (OMDQ) Overall Health Score at Varying Cumulative Radiation Doses (Gy)(Baseline and up to 12 weeks)
- Mean Change From Baseline in C-reactive Protein (CRP) Values at Varying Weeks(Baseline and up to 12 weeks)