A Phase 2 Study of the MET RTK Inhibitor GSK1363089 (Formerly XL880) in Subjects With Recurrent or Metastatic Squamous Cell Cancer of the Head and Neck
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 14
- 试验地点
- 1
- 主要终点
- Number of Participants With Abnormalities of Common Toxicity Criteria for Adverse Events (CTCAE) Grade 3 in Laboratory Parameters (Clinical Chemistry and Hematology)
研究概览
简要总结
This study is being conducted to determine the best confirmed response rate, safety, and tolerability of GSK1363089 treatment in adult subjects with squamous cell carcinoma of the head and neck (SCCHN). GSK1363089 is a new chemical entity that inhibits multiple receptor tyrosine kinases (RTKs) with growth-promoting and angiogenic properties. The primary targets of GSK1363089 are the HGF and vascular endothelial growth factor (VEGF) RTK families (eg, MET, VEGFR2/kinase insert domain receptor [KDR]). Since MET overexpression has been associated with poorer prognosis and MET tyrosine kinase mutations have been reported in SCCHN, inhibition of MET receptor and VEGFR2/KDR activation by agents such as GSK1363089 may be of therapeutic benefit in this patient population.
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
- •The subject has a histologically or cytologically confirmed diagnosis of SCCHN and
- •has recurrent and/or metastatic disease
- •is not eligible for curative intent surgery or radiotherapy
- •has no history of uncontrolled tumor bleeding including hemoptysis in patients with documented pulmonary metastasis.
- •The subject has measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as =20 mm with conventional techniques, or as =10 mm with spiral computerized tomography (CT) scan.
- •Subject is capable of swallowing capsules.
- •Fifteen unstained slides of tumor tissue, archival or fresh, or paraffin block are available, and there - confirmation that samples have been sent for analysis at the central laboratory.
- •The subject is at least 18 years old.
- •The subject has an Eastern Cooperative Oncology Group (ECOG) performance status =
- •In the adrenocorticotropic hormone (ACTH) stimulation test, the subject has a serum cortisol level =20 µg/dL (552 nmol/L) 30-90 minutes after injection of ACTH.
- •The subject has organ and marrow function as follows: absolute neutrophil count (ANC) =1500/mm3, platelets =100,000/mm3, hemoglobin =9 g/dL, bilirubin =1.5 mg/dL, serum creatinine =1.5 mg/dL and/or calculated creatinine clearance =60 mL/min, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =2.5 times the upper limit of normal if no liver involvement or =5 times the upper limit of normal with liver involvement.
- •The subject has signed the informed consent document.
- •Sexually active subjects must use a medically accepted method of contraception during the course of the study.
- •Female patients of childbearing potential must have a negative pregnancy test at enrollment.
- •The subject has had no other diagnosis of malignancy (unless non-melanoma skin cancer, in situ carcinoma of the cervix, or a malignancy diagnosed =5 years ago, and has had no evidence of disease for 5 years prior to screening for this study).
排除标准
- •The subject has received radiation to >25% of his or her bone marrow within 30 days of GSK1363089 treatment.
- •The subject has received an investigational drug within 30 days (or <5.5 half lives) of the first dose of study drug.
- •The subject has received more than one regimen of systemic anticancer therapy for disease that has recurred or is metastatic. This may include either single-agent or combination cytotoxic chemotherapy with radiotherapy or anti-EGFR treatment (eg, cetuximab). Adjuvant or neoadjuvant systemic chemotherapy does not count as a regimen for recurrent or metastatic disease.
- •The subject has progressed within 6 months after completion of curative intent (definitive) treatment for localized/locoregionally advanced disease.
- •The subject has not recovered to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0 Grade =1 from adverse events (AEs) due to investigational drugs or other medications that were administered more than 30 days before study enrollment with the sole exception of persistent Grade 2 peripheral neuropathy in patients who have previously received platinum-based therapy.
- •The subject has known brain metastases.
- •The subject has uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, active alcoholism, or psychiatric illness that would limit compliance with study requirements.
- •The subject is pregnant or breastfeeding.
- •The subject is known to be positive for the human immunodeficiency virus (HIV).
- •The subject has an allergy or hypersensitivity to components of the GSK1363089 formulation.
研究组 & 干预措施
Single Arm
Participants who qualified for study entry received 240 mg of GSK1363089 (foretinib) on a 5-day on 9-day off schedule every 2 weeks.
干预措施: GSK1363089 (foretinib) (Drug)
结局指标
主要结局
Number of Participants With Abnormalities of Common Toxicity Criteria for Adverse Events (CTCAE) Grade 3 in Laboratory Parameters (Clinical Chemistry and Hematology)
时间窗: Up to 20 months
The National Cancer Institute -CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each toxicity based on the following general guideline: Grade 1: Mild AE, Grade 2: Moderate AE, Grade 3: Severe AE, Grade 4: Life-threatening or disabling AE and Grade 5: Death related to AE. Number of participants with abnormalities of CTCAE grade 3 in clinical chemistry parameters: alanine aminotransferase (ALT), γ-glutamyl transferase (GGT), phosphate, low sodium and hematology parameters: Leukocyte and Lymphocytes were presented.
Number of Participants Achieving Best Overall Response
时间窗: Approximately up to 1 year
Best overall response was assessed by the investigator per response evaluation criteria in solid tumors (RECIST). Per RECIST v1.0 for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. Tumor size was recorded at Baseline, and tumor response were recorded approximately every 8 weeks. Tumor response were classified by the investigator using RECIST criteria participant's best response whether observed in the study treatment period or the treatment extension period was considered. The best overall response was the best response recorded from the start of treatment until disease progression/recurrence. Number of participants who achieved best overall response were recorded.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: Up to 20 months
Data for number of participants who presented one or more adverse events (serious or non serious) was reported. An AE was defined as any untoward medical occurrence (MO) in a participant temporally associated with the use of a medicinal product (MP), whether or not considered related to the MP and can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with its use. The SAE was any untoward MO that, at any dose, results in death, life threatening, persistent or significant disability/incapacity, results in or prolongs inpatient hospitalization, congenital abnormality or birth defect, that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition.
Percentage of Participants With Objective Response Rate (ORR)
时间窗: Approximately up to 1 year
ORR was defined as the proportion of participants achieving best overall response of confirmed CR or PR divided by the total number of participants who received treatment. Per RECIST v1.0 for target lesions and assessed by MRI: CR, Disappearance of all target lesions; Partial Response PR, \>=30% decrease in the sum of the longest diameter of target lesions; OR = CR + PR. Participants were evaluated for tumor response per RECIST. Percentage of participants with ORR were reported.
Number of Participants With Abnormalities in Urinalysis
时间窗: Week 5 [Day 29]
Urinalysis parameters like appearance, color, pH, specific gravity, ketones, protein, glucose, bilirubin, nitrite, urobilinogen, and occult blood were performed. Number of participants with abnormalities are reported. In case of no abnormalities observed then it is reported as zero.
次要结局
- Duration of Progression-free Survival(Approximately up to 1 year)
- Duration of Overall Survival(Approximately up to 1 year)
- Duration of Stable Disease(Approximately up to 1 year)
- Percentage Participants With Disease Stabilization Rate(Approximately up to 1 year)
- Maximum Plasma Concentration (Cmax) of Foretinib in Participants With Squamous Cell Carcinoma of the Head and Neck (SCCHN)(Day 1, 5, 19, 33, 43, 47 (pre-dose15 min) and 4 h (± 30 min) post-dose)
- Time to Maximum Plasma Concentration (Tmax) of Foretinib in Participants With SCCHN(Day 1, 5, 19, 33, 43, 47 (pre-dose15 min) and 4 h (± 30 min) post-dose)
- Area Under the Concentration-time Curve (AUC) of Foretinib in Participants With SCCHN(Day 1, 5, 19, 33, 43, 47 (pre-dose15 min) and 4 h (± 30 min) post-dose)
- Elimination Half-life (t1/2) of Foretinib in Participants With SCCHN(Day 1, 5, 19, 33, 43, 47 (pre-dose15 min) and 4 h (± 30 min) post-dose)
- Apparent Oral Clearance(Day 1, 5, 19, 33, 43, 47 (pre-dose15 min) and 4 h (± 30 min) post-dose)
- Apparent Volume of Distribution(Day 1, 5, 19, 33, 43, 47 (pre-dose15 min) and 4 h (± 30 min) post-dose)