A Randomized Phase II Trial of Cisplatin With or Without Wee1 Kinase Inhibitor AZD1775 (MK-1775) for First-line Treatment of Recurrent or Metastatic Squamous Cell Cancer of the Head and Neck (RM-SCCHN)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 6
- 试验地点
- 3
- 主要终点
- Overall Response Rate (Complete Plus Partial Response) Using RECIST Criteria v1.1
研究概览
简要总结
This randomized phase II trial studies how well cisplatin with or without WEE1 inhibitor MK-1775 works in treating patients with head and neck cancer that has come back or has spread to other parts of the body. Drugs used in chemotherapy, such as cisplatin, may prevent tumor cells from multiplying by damaging their deoxyribonucleic acid (DNA), which in turn stops the tumor from growing. WEE1 inhibitor MK-1775 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether cisplatin is more effective with or without WEE1 inhibitor MK-1775 in treating patients with head and neck cancer.
详细描述
PRIMARY OBJECTIVES:
I. To compare the overall response rate assess the efficacy of MK-1775 (WEE1 inhibitor MK-1775) in combination with cisplatin to cisplatin alone in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) as per overall response rate (using Response Evaluation Criteria in Solid Tumors [RECIST] criteria version [v]1.1).
SECONDARY OBJECTIVES:
I. Assess secondary measures of efficacy (progression free survival at 6 months and 12 months, overall survival rate at 12 months).
II. Assess measures of efficacy by tumor protein (p)53 status. III. Evaluate safety and tolerability. IV. Explore predictive and pharmacodynamic biomarkers.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 19 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must have histologically or cytologically confirmed SCCHN that is recurrent and/or metastatic and not amendable to curative therapy by surgery or radiation; SCCHN originating from the following sites are eligible: oral cavity, oropharynx, larynx, hypopharynx and paranasal sinus; for patients with a diagnosis of SCCHN of unknown origin, their eligibility must be reviewed and approved by the principal investigator
- •No prior systemic chemotherapy or WEE1 kinase inhibitor therapy for metastatic or recurrent disease will be allowed; patients are permitted to have received prior systemic chemotherapy as a part of the initial multimodality treatment for locally advanced disease if this treatment was completed more than 6 months prior to enrollment
- •Patients must have disease amenable to biopsy and must be medically fit to undergo a biopsy
- •Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as > 10 mm with computed tomography (CT) scan; indicator lesions must not have been previously treated with surgery, radiation therapy or radiofrequency ablation unless there is documented progression after therapy
- •Patients must have completed any previous surgery or radiotherapy >= 4 weeks prior to enrollment
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (Karnofsky > 60%)
- •Life expectancy of greater than 12 weeks
- •Leukocytes >= 3,000/mcL
- •Absolute neutrophil count >= 1,500/mcL
- •Platelets >= 100,000/mcL
- •Hemoglobin >= 9 g/dL
- •Total bilirubin within normal institutional limits
- •Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 × institutional upper limit of normal
- •Prothrombin time (PT)/partial thromboplastin time (PTT)/international normalized ratio (INR) =< 1.5 upper limit of normal (ULN)
- •Creatinine within normal institutional limits OR calculated creatinine clearance >= 60 mL/min/1.73 m^2 for patients with levels above institutional normal using modified Cockcroft-Gault
- •Cardiac function: 12-lead electrocardiogram (ECG) with normal tracing, or non-clinically significant changes that do not require medical intervention; corrected QT (QTc) interval is to be < 470 msec
- •Women of childbearing potential and men must be surgically sterilized, practicing abstinence, or agree to use 2 birth control methods prior to study entry and for the duration of study participation including up to 30 days after the last dose of MK-1775; the 2 methods of birth control can be either 2 barrier methods or a barrier method plus a hormonal method to prevent pregnancy; the following are considered adequate barrier methods of contraception: diaphragm or sponge, and condom; other methods of contraception such as copper intrauterine device or spermicide may be used; appropriate hormonal contraceptives will include any registered and marketed contraceptive agent that contains an estrogen and/or a progestational agent (including oral, subcutaneous, intrauterine, or intramuscular agents); should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
- •Ability to understand and the willingness to sign a written informed consent document
排除标准
- •Past or current malignancy other than SCCHN, except for:
- •Cervical carcinoma stage 1B or less
- •Non-invasive basal cell and squamous cell skin carcinoma
- •Malignant melanoma with a complete response of a duration of > 10 years
- •Radically treated prostate cancer (prostatectomy or radiotherapy) with normal prostate specific antigen (PSA), and not requiring ongoing anti-androgen hormonal therapy
- •Other cancer diagnosis with a complete response of duration of > 5 years
- •Patients may not be receiving any other investigational agents
- •Patients with known brain metastases should be excluded from this clinical trial
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to MK-1775 or cisplatin
- •Patients who are unable to take oral medications and/or who have a clinical or radiological diagnosis of bowel obstruction are ineligible
- •Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, active peptic ulcer disease, myocardial infarction within 6 months prior to entry, congestive heart failure, symptomatic congestive heart failure, active cardiomyopathy, unstable angina pectoris, cardiac arrhythmia, uncontrolled hypertension or psychiatric illness/social situations that would limit compliance with study requirements
- •Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with MK-1775
- •Human immunodeficiency virus (HIV)-positive patients are ineligible
- •Patients taking the following prescription or non-prescription drugs or other products (i.e. grapefruit juice) are ineligible: sensitive cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) substrates, CYP3A4 substrates with a narrow therapeutic index, moderate to potent inhibitors/inducers of CYP3A4; patients would be eligible if the medications can be discontinued two weeks prior to day 1 of dosing and withheld throughout the study until 2 weeks after the last dose of study medication
研究组 & 干预措施
Arm I (WEE1 inhibitor MK-1775, cisplatin)
Patients receive WEE1 inhibitor MK-1775 PO BID for 5 doses beginning on day 1 and cisplatin IV over 1 hour on day 1.
干预措施: Cisplatin (Drug)
Arm I (WEE1 inhibitor MK-1775, cisplatin)
Patients receive WEE1 inhibitor MK-1775 PO BID for 5 doses beginning on day 1 and cisplatin IV over 1 hour on day 1.
干预措施: Laboratory Biomarker Analysis (Other)
Arm I (WEE1 inhibitor MK-1775, cisplatin)
Patients receive WEE1 inhibitor MK-1775 PO BID for 5 doses beginning on day 1 and cisplatin IV over 1 hour on day 1.
干预措施: Pharmacological Study (Other)
Arm I (WEE1 inhibitor MK-1775, cisplatin)
Patients receive WEE1 inhibitor MK-1775 PO BID for 5 doses beginning on day 1 and cisplatin IV over 1 hour on day 1.
干预措施: WEE1 Inhibitor AZD1775 (Drug)
Arm II (placebo, cisplatin)
Patients receive placebo PO BID for 5 doses beginning on day 1 and cisplatin IV over 2 hour on day 1.
干预措施: Cisplatin (Drug)
Arm II (placebo, cisplatin)
Patients receive placebo PO BID for 5 doses beginning on day 1 and cisplatin IV over 2 hour on day 1.
干预措施: Laboratory Biomarker Analysis (Other)
Arm II (placebo, cisplatin)
Patients receive placebo PO BID for 5 doses beginning on day 1 and cisplatin IV over 2 hour on day 1.
干预措施: Pharmacological Study (Other)
Arm II (placebo, cisplatin)
Patients receive placebo PO BID for 5 doses beginning on day 1 and cisplatin IV over 2 hour on day 1.
干预措施: Placebo (Other)
结局指标
主要结局
Overall Response Rate (Complete Plus Partial Response) Using RECIST Criteria v1.1
时间窗: Up to 1 year
Per Response Evaluation Criteria in solid Tumors (RECIST1.1) Target lesions are assessed as Complete Response(CR), Disappearance of all target lesions; Partial Response (PR),30% decrease in the sum of the diameters of target lesions; Progressive Disease (PD), At least a 20% increase (minimum 5 mm) from smallest sum (nadir); Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Nontarget lesions are assessed as Complete Response (CR), Disappearance of all non-target lesions; Non-CR/Non-PD, Persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits; Progressive Disease (PD),Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions; Overall Response(OR); PR=CR+non-CR/non-PD,SD=SD+non-PD; PD=PD+presence of any non-target lesions
次要结局
- Levels of Predictive Biomarkers(Up to day 4 of course 1)
- Overall Survival(12 months)
- Progression Free Survival(Time from start of treatment to time of progression or death, whichever occurs first, assessed at 12 months)
- Incidence of Adverse Events Using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0(Up to 1 year)
- Levels of Pharmacodynamic Biomarkers(Pre-dose, at 4-8 hours on day 3 or 20-24 hours on day 4)