A 2 Cohort, Non-comparative, Pivotal Study Evaluating the Efficacy of Tipifarnib in Patients With Head and Neck Squamous Cell Carcinoma (HNSCC) With HRAS Mutations (AIM-HN) and the Impact of HRAS Mutations on Response to First Line Systemic Therapies for HNSCC (SEQ-HN)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 296
- 试验地点
- 101
- 主要终点
- Objective Response Rate (ORR) in High Variable Allele Frequency (VAF) Population, as Assessed by Independent Review Facility (IRF)
研究概览
简要总结
An international, multicenter, open-label, 2 cohort, non-comparative, pivotal study evaluating the efficacy of tipifarnib in HRAS mutant HNSCC (AIM-HN). The first cohort will assess the objective response rate (ORR) of tipifarnib in subjects with HNSCC with HRAS mutations. The second study cohort, SEQ-HN, is an observational sub-study including HNSCC patients in whom HRAS mutations were not identified (wild type HRAS HNSCC) and who consent to provide first line outcome data and additional follow up.
详细描述
KO-TIP-007 is an international, multicenter, open-label, 2 cohort, non-comparative, pivotal study evaluating the efficacy of tipifarnib in HRAS mutant HNSCC (AIM-HN) and the impact of HRAS mutations on response to first line systemic therapies for HNSCC (SEQ-HN). KO-TIP-007 has 2 study cohorts. The first study cohort, named AIM-HN, includes HNSCC subjects with HRAS mutations. AIM-HN subjects will receive treatment with tipifarnib and the outcome of this cohort will be evaluated for ORR by an independent review facility.
The second study cohort, SEQ-HN, is an observational sub-study including HNSCC patients in whom HRAS mutations were not identified (wild type HRAS HNSCC) and who consent to provide first line outcome data and additional follow up.
HNSCC patients in whom HRAS mutations are identified and who meet eligibility criteria will be offered participation in AIM-HN. HNSCC patients in whom HRAS mutations are not identified may participate in SEQ-HN only. These patients will be followed and the comparison of outcomes of HRAS mutant and HRAS wild type HNSCC will address the exploratory objective to determine the effect of HRAS mutation on the ORR of first line systemic therapy in patients with recurrent/metastatic HNSCC. Outcome data from subsequent lines of therapy will be collected.
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
- •At least 18 years of age.
- •Histologically confirmed head and neck cancer (oral cavity, pharynx, larynx, sinonasal, nasopharyngeal, or unknown primary) of squamous histology not amenable to local therapy with curative intent (surgery or radiation therapy with or without chemotherapy).
- •Documented treatment failure from most recent prior therapy (e.g. tumor progression, clinical deterioration, or recurrence), and from at least one prior platinum-containing regimen, in any treatment setting.
- •Known tumor missense HRAS mutation.
- •Measurable disease by RECIST v1.
- •ECOG performance status of 0-
- •Acceptable liver, renal and hematological function
- •Other protocol defined inclusion criteria may apply.
排除标准
- •Histologically confirmed salivary gland, thyroid, (primary) cutaneous squamous or nonsquamous histologies (e.g. mucosal melanoma).
- •Received treatment for unstable angina within prior year, myocardial infarction within the prior year, cerebro-vascular attack within the prior year, history of New York Heart Association grade III or greater congestive heart failure, or current serious cardiac arrhythmia requiring medication except atrial fibrillation.
- •Non-tolerable Grade 2 or ≥ Grade 3 neuropathy or evidence of unstable neurological symptoms within 4 weeks of Cycle 1 Day
- •Active, uncontrolled bacterial, viral or fungal infections requiring systemic therapy. Known history of infection with human immunodeficiency virus or an active infection with hepatitis B or hepatitis C.
- •Received treatment for non-cancer related liver disease within prior year.
- •Other protocol defined exclusion criteria may apply
- •Inclusion Criteria: SEQ-HN
- •At least 18 years of age.
- •Histologically confirmed head and neck cancer (oral cavity, pharynx, larynx, sinonasal, nasopharyngeal, or unknown primary) of squamous histology.
- •Will or has received at least one systemic anti-cancer therapy for recurrent or metastatic HNSCC.
- •HRAS wildtype (i.e., have no identified tumor missense HRAS mutation).
- •Other protocol defined inclusion criteria may apply
- •Exclusion Criteria: SEQ-HN
- •Histologically confirmed salivary gland, thyroid, (primary) cutaneous squamous or nonsquamous histologies (e.g. mucosal melanoma).
- •Other protocol defined exclusion criteria may apply
研究组 & 干预措施
AIM-HN
Tipifarnib, Oral Tablet. Dose Level 1 orally, bid on days 1-7 and 15-21 of 28-day treatment cycles
干预措施: Tipifarnib (Drug)
AIM-HN
Tipifarnib, Oral Tablet. Dose Level 1 orally, bid on days 1-7 and 15-21 of 28-day treatment cycles
干预措施: HRAS Detection Assay (Device)
结局指标
主要结局
Objective Response Rate (ORR) in High Variable Allele Frequency (VAF) Population, as Assessed by Independent Review Facility (IRF)
时间窗: Up to approximately 28 months
ORR was defined as the percentage of participants who experienced a best overall response (BOR) of complete response (CR; disappearance of all target lesions) or partial response (PR; at least a 30% decrease in the sum of diameters of target lesions) and was assessed using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by IRF. 95% confidence interval (CI) was calculated by the exact binomial (Clopper-Pearson) method.
次要结局
- Progression Free Survival (PFS) in High VAF Population, as Assessed by IRF(Up to approximately 28 months)
- ORR in All VAF Population, as Assessed by IRF(Up to approximately 28 months)
- Duration of Response (DoR) in High VAF Population, as Assessed by IRF(Up to approximately 28 months)
- DoR in All VAF Population, as Assessed by IRF(Up to approximately 28 months)
- PFS in All VAF Population, as Assessed by IRF(Up to 28 approximately months)
- PFS Rate in High VAF Population, as Assessed by IRF(6 months and 9 months)
- PFS Rate in All VAF Population, as Assessed by IRF(6 months and 9 months)
- Overall Survival (OS) in High VAF Population(Up to approximately 28 months)
- OS in All VAF Population(Up to approximately 28 months)
- OS Rate at 12 Months in High VAF Population(12 months)
- OS Rate at 12 Months in All VAF Population(12 months)
- Time to Response (TTR) in High VAF Population, as Assessed by IRF(Up to approximately 28 months)
- TTR in All VAF Population, as Assessed by IRF(Up to approximately 28 months)
- Number of Participants Who Experienced Treatment-Emergent Adverse Events (TEAEs)(Up to approximately 28 months)
- Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Head and Neck Module 35 (EORTC QLQ-H&N35) Subscales(Baseline and End of Treatment Visit (up to approximately 28 months))
- Change From Baseline in the EuroQol-Visual Analog Scale (EQ-VAS) Score(Baseline and End of Treatment Visit (up to approximately 28 months))