An Open-label, International, Multi-Center, Phase I/II, Dose-escalation Trial Investigating the Safety of Zalutumumab, a Human Monoclonal Epidermal Growth Factor Receptor Antibody in Combination With Radiotherapy, in Patients With Stage III, IVa or IVb Locally Advanced Squamous Cell Carcinoma of the Head and Neck Ineligible for Platinum Based Chemotherapy
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Genmab
- 入组人数
- 8
- 试验地点
- 8
- 主要终点
- Number of Participants With Adverse Events (AEs)
研究概览
简要总结
The purpose of this study is to investigate the safety of zalutumumab in combination with radiotherapy as the treatment of patients with head and neck cancer who are not eligible for platinum based chemotherapy.
详细描述
This is an open label, multi-center, phase I/II dose-escalation clinical trial investigating the safety of zalutumumab in combination with radiotherapy. The safety of zalutumumab doses in combination with radiotherapy (RT) will be investigated using 3 patient cohorts in a dose-escalation / de-escalation design based on Dose Limiting Toxicity (DLT). The dose-escalation starts at 8 mg/kg zalutumumab in combination with RT. Initially, three patients will be treated at a dose level and observed for DLTs. If none of the three patients experience a DLT, then the next cohort of three patients is treated at the next higher dose of zalutumumab. If one of three patients treated at a dose level experience a DLT, then three more patients are treated at the same dose level. If two or more of the three patients experience DLTs, then the next cohort of three patients should be treated at the next lower dose of zalutumumab, unless at least six patients on that dose have already been dosed. Furthermore, if 1 or fewer DLTs are observed among six patients at a given dose level, then the next cohort of three patients is treated at the next higher dose of zalutumumab. The maximum tolerated dose will be decided by Genmab based on the recommendations made by the IDMC on the basis of their review of the aggregated safety data.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
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
- •Patients with histologically or cytologically confirmed diagnosis of locally advanced squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx stage III, IVa or IVb
- •Measurable disease defined as one or more target lesions according to RECIST based onCT scan or MRI and clinical evaluation
- •Eligible for intended curative radiotherapy
- •Patients considered ineligible for platinum based chemotherapy based on investigator's judgment
- •Age > 18 years
- •Following receipt of verbal and written information about the study, the patient must provide signed informed consent before any study related activity is carried out
排除标准
- •Prior radiotherapy to the head and neck area
- •Prior chemotherapy administered for cancer in the head and neck area
- •Prior targeted therapy (e.g. EGFR antibodies or EGFR inhibitors)
- •Received the following treatments within 4 weeks prior to Visit 2:
- •Retinoic acid
- •Other immunosuppressive drugs (e.g. drugs interfering with the functions of T cells, IL-2 or equivalent)
- •Any non-marketed drug substance
- •Past or current malignancy other than SCCHN, except for:
- •Cervical carcinoma Stage 1B or less
- •Non-invasive basal cell skin carcinoma
- •Squamous cell skin carcinoma
- •Stage 1 or 2 treated prostate cancer with PSA in the normal range for >2 years post treatment
- •Malignant melanoma with a complete response duration of > 10 years
- •Other cancer diagnoses with a complete response duration of > 5 years
- •Metastatic SCCHN disease
- •Chronic or current infectious disease such as, but not limited to, chronic renal infection and tuberculosis
- •Clinically significant cardiac disease including unstable angina, acute myocardial infarction within six months before Visit 1, congestive heart failure, and arrhythmia requiring anti-arrhythmic therapy, with the exception of extra systoles or minor conduction abnormalities
- •Significant concurrent, uncontrolled medical condition including, but not limited to,hepatic, hematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease considered to preclude trial treatment and/or compliance according to the Investigator's opinion, or any other condition preventing therapy according to the Investigator's opinion
- •Known HIV positive
- •Known active hepatitis B and/or hepatitis C
- •Screening laboratory values:
- •Neutrophils < 1.5 x 109/L
- •Platelets < 100 x109/L
- •Hemoglobin < 6 mmol/L
- •Current participation in any other interventional clinical study
- •Patients known or suspected of not being able to comply with a study protocol (e.g. due to alcoholism, drug dependency, or psychological disorder)
- •Known or suspected hypersensitivity to components of the investigational medicinal Product
- •Breast feeding women or women with a positive pregnancy test at screening blood Sample
- •Males not willing to use adequate contraception during study and for 12 months after last dose of zalutumumab or women of childbearing potential not willing to use adequate contraception as hormonal birth control or intrauterine device during study and for 12 months after last dose of zalutumumab
研究组 & 干预措施
Zalutumumab 4 mg/kg
Zalutumumab in combination with radiotherapy for 8 weeks. The treatment period of 8 weeks is followed by a 3 week follow-up period where all adverse events are collected and then additionally a 2 year follow-up period where only serious adverse events are collected.
干预措施: Zalutumumab (Drug)
Zalutumumab 8 mg/kg
Zalutumumab in combination with radiotherapy for 8 weeks. The treatment period of 8 weeks is followed by a 3 week follow-up period where all adverse events are collected and then additionally a 2 year follow-up period where only serious adverse events are collected.
干预措施: Zalutumumab (Drug)
结局指标
主要结局
Number of Participants With Adverse Events (AEs)
时间窗: From first dose date up to end of the safety follow up period (Up to 2 years)
Number of participants with at least one adverse event. All adverse events are collected during 12 weeks and all serious adverse events are collected during 2 years.
次要结局
- Number of Participants With Best Overall Tumour Response(Up to 2 years)
- Number of Participants With Objective Response(Up to 2 years)