A Phase 1/2a Multicenter, Open-Label, Dose-Escalation, Combination Study of RM-1929 and Photoimmunotherapy in Patients With Recurrent Head and Neck Cancer, Who in the Opinion of Their Physician, Cannot Be Satisfactorily Treated With Surgery, Radiation or Platinum Chemotherapy
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 14
- 主要终点
- Part I: Photosafety (sunburn) Testing
研究概览
简要总结
This is a two-part clinical study of patients with recurrent Head and Neck Cancer (HNC), who in the opinion of their physician, cannot be satisfactorily treated with surgery, radiation or platinum chemotherapy. The purpose of the study is to determine the safety and anti-cancer activity of various doses and repeated cycles of the experimental treatment using the study drug RM-1929 and fixed amounts of red light applied at the tumor site to activate the pharmacodynamics of the drug.
The part 1 of the study has been completed and consisted in a single cycle, 3+3 dose escalation safety study of the experimental drug RM-1929 using a fixed amount of 690 nm red light. The part 1 was designed to determine the safety of the treatment as set by the maximal feasible dose or the maximal tolerable dose of RM-1929. From the part 1 results, the maximal feasible dose of RM-1929 was determined.
The part 2 of the study is currently ongoing and it is evaluating the safety and anticancer efficacy of up to four repeated treatments of Photoimmunotherapy with RM-1929 at the maximal feasible dose of RM-1929 activated with a fixed amount of red light.
详细描述
Photoimmunotherapy (PIT) is a new cancer targeted technology invented at the National Cancer Institute, USA. This clinical study evaluates the treatment of the experimental drug RM-1929 with Photoimmunotherapy (PIT).
The experimental drug, RM-1929, is a parental formulation consisting of a chemical conjugate of the dye IR700 with the FDA approved antibody, Erbitux® (Cetuximab), that targets EGFR receptors (EGFR is a cancer expressed protein, a cancer antigen). EGFR is highly expressed in squamous cell carcinomas of the head and neck (HNSCC). It is expected that systemic administration of RM-1929 will lead to tumor accumulation and binding to EGFR expressed at cancer cells. It is expected that treatment with RM-1929 and Photoimmunotherapy can lead to the selective destruction of the HNSCC cancer cells and provide an effective therapy to manage the disease.
The treatment using RM-1929 with Photoimmunotherapy requires two steps:
(i) the administration by infusion of the drug RM-1929 targeting the cancer protein EGFR
AND
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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 must meet the following criteria to be eligible for study participation:
- •Patients with recurrent squamous carcinoma of the Head and Neck, who in the opinion of their treating physician, cannot be satisfactorily treated with surgery, radiation, or platinum chemotherapy. Diagnosis must be confirmed by biopsy and histopathology.
- •Patient must have received prior systemic platinum-based chemotherapy for treatment of their head and neck cancer, unless in the opinion of the medical oncologist, the use of platinum-based chemotherapy is contraindicated or not recommended, e.g., renal impairment, allergy to platinum compounds, age, liver disease, myelosuppression, neuropathy, hearing loss, etc.
- •Patients must have life expectancy > 6 months based on investigator judgment.
- •Male or female patients at least 18 years old. Female patients must not be pregnant or breast feeding and must be practicing a medically acceptable form of birth control, be sterile, or post-menopausal. Females of childbearing potential (FCBP) is defined as premenopausal women capable of becoming pregnant. This includes women who are post-menopausal for at least 12 months after the last menses. FCBP must agree to use a medically acceptable form of birth control during the study and for at least 6 months after discontinuation of Erbitux® or study medication. Females must agree not to breast feed during the study and for at least two months after discontinuation of Erbitux® or study medication. Male patients should be using a double barrier protection method that is a medically acceptable form of birth control during the study or be sterile.
- •Patients must have an ECOG score of 0 -
- •Patient must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure.
排除标准
- •Patients with any of the following will be excluded from participation in the study:
- •Patients with a history of significant Erbitux infusion reactions (≥ Grade 3).
- •Patients on chemotherapy or Erbitux® therapy or radiation therapy within 4 weeks of enrollment.
- •Tumor invading a major blood vessel (such as the carotid artery) unless the vessel has been embolized, stented or surgically ligated to prevent hemorrhage.
- •Tumor is not clearly shown on a CT scan or clinically measurable.
- •Location and extension of the tumor precludes an effective PIT.
- •Patients with impaired hepatic function (ALP (hepatic), AST and/or ALT >3 times the upper normal limits, or total serum bilirubin > 2 mg/dL.
- •Patients with impairment of renal function (serum creatinine >2 mg/dL).
- •Unwilling or unable to follow protocol requirements.
- •Any condition which in the Investigator's opinion deems the patient an unsuitable candidate to receive study drug.
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- •Patient requires examinations or treatments within 4 weeks after study drug administration where they would be exposed to significant light, e.g., eye examinations, surgical procedures, endoscopy, etc.
结局指标
主要结局
Part I: Photosafety (sunburn) Testing
时间窗: 1 month
Determination of skin Minimal Erythema Dose (MED) following infusion of RM-1929
Part I: Maximum Tolerated Dose (MTD) or Maximum Feasible Dose (MFD) of RM-1929, whichever is lowest
时间窗: 1 month
Determine the MTD or MFD of RM-1929
Part I: Adverse Event profile for each drug dose of RM-1929
时间窗: 1 month
Assessment of safety of the combination of drug dose with low energy localized light irradiation
Part II: Maximum Tolerated Dose (MTD) or Maximum Feasible Dose (MFD) of a fixed drug dose with fixed light dose
时间窗: 1 month
Determination of MTD or MFD of fixed drug dose with fixed light dose
Part II: Safety with repeat dosing
时间窗: 2 years or until death
Safety parameters associated with repeat dosing
次要结局
- Part I: Pharmacokinetics of RM-1929 and for both RM-1929 and unconjugated IRDye 700DX (Cmax, T 1/2, AUC, CL and Vss)(1 month)
- Part I: Immunogenic response to RM-1929(2 month)
- Part II: Tumor Response(2 months)
- Part I: Tumor response(2 months)
- Part II: Tumor Reduction(2 months)
- Part 1: Tumor reduction/necrosis(2 month)
- Part II: Immunogenic response to RM-1929(2 months)