A Phase 1 Study of Oral MRX-1024 in Combination With Standard Fractionation Radiation Therapy and High-Dose Cisplatin in Patients With Squamous Cell Carcinoma of the Head and Neck Following Surgical Resection
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 主要终点
- Determine pharmacokinetic parameters of oral MRX-1024.
研究概览
简要总结
Rationale for Study
Oral mucositis is a major complication arising from contemporary chemoradiation treatment of patients with head and neck cancer.
No effective therapy exists to prevent this complication in this population. MRX-1024 is an investigational agent that has demonstrated in in vitro and in vivo experiments to have the potential to exert a protective effect in normal mucosa cells, without interfering with the intended antitumor effect of radiation.
A pilot Phase 1 study of MRX-1024 was conducted in India in patients with head and neck cancer receiving radiation alone or radiation in combination with cisplatin or carboplatin. MRX 1024 doses of 100 mgkg given orally twice a day, five days a week during radiation treatment cycles, were well tolerated and appeared to exert a protective effect against the development of severe mucositis.
Twice daily doses of MRX 1024 impose a certain level of inconvenience to the patient, to their clinic companion, and to the general work flow within radiation oncology clinics.
This study is designed to study the safety and pharmacokinetics of both single daily dose and twice daily dose regimens of oral MRX 1024 given in conjunction with daily radiation fractions and intermittent high-dose cisplatin to patients with high-risk for recurrence head and neck cancer following surgical resection. The study will also document the incidence and severity of oral mucositis that occurs following such therapy. The results will be instrumental in determining the regimen of MRX 1024 to use in subsequent definitive clinical trials.
详细描述
TREATMENT PLAN
Study Phases
Each patient progresses through five study phases.
MRX 1024 Cohorts, Dose Levels and Treatment
Five successive dose levels are planned.
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
- •Biopsy-proved squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx or larynx;
- •Status-post surgical resection of primary disease and meeting criteria for post-operative radiotherapy and chemotherapy by evidence of histologic extracapsular nodal extension, or histologic involvement of >2 regional lymph nodes, or mucosal margin of resection with invasive cancer (limited to microscopic detection only);
- •Able to begin protocol treatment within 8 weeks of first tumor-related surgery;
- •Age >18 years. Because no dosing or adverse event data are currently available on the use of MRX-1024 in combination with radiotherapy and cisplatin or carboplatin, in patients less than 18 years of age, children are excluded from this study, but will be eligible for future pediatric Phase 1 combination studies in appropriate indications when sufficient safety and efficacy data in adults are available.
- •Karnofsky Performance Status of >70 (Appendix I);
- •Normal organ and marrow function as defined herein, determined by laboratory values obtained within seven days prior to receiving the first dose of protocol treatment:
- •Serum creatinine within institutional limits of normal
- •Creatinine clearance >50
- •Total bilirubin within institutional limits of normal
- •AST(SGOT) and ALT(SGPT) <2.5 times the upper limit of normal for the institution
- •White blood cell count >3500 per cubic millimeter
- •Absolute neutrophil count >1500 per cubic millimeter
- •Platelet count >100,000 per cubic millimeter
- •Ability to understand and the willingness to sign an informed consent document in accordance with institutional guidelines.
排除标准
- •Gross (visible or palpable) disease left after surgical resection;
- •Prior chemotherapy or radiation therapy to the head and neck region;
- •Primary site of the lip, nasopharynx or paranasal sinuses;
- •Distant metastases;
- •Known malabsorption syndrome;
- •Pregnancy or breast-feeding. The effects of MRX-1024 on the developing human fetus are unknown at this time. For this reason, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) for the duration of study participation. Should a woman become pregnant or suspect that she is pregnant while participating in this study, she should inform her treating physician immediately;
- •Gastrointestinal tract disease or deformity resulting in an inability to take oral or enteral medication or nutrition;
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, untreated or new cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements;
- •History of taking any investigational medication within 4 weeks prior to receiving the first dose of protocol treatment.
- •Prior malignancy within the previous 5 years, excluding non-melanoma skin cancer and cervical cancer treated with local therapy.
- •Known allergy or sensitivity to polysorbate 80 (Tween).
结局指标
主要结局
Determine pharmacokinetic parameters of oral MRX-1024.
Identify toxicity profile of oral MRX-1024.
safe recommended doses and dose regimen for oral MRX-1024 with concurrent chemoradiation.
次要结局
- Possibly show a trend in activity of MRX-1024 in preventing or reducing oral mucositis.