Phase I Trial of ATR Inhibitor Camonsertib Combined With Stereotactic Body Radiation Therapy for Recurrent Head and Neck Squamous Cell Carcinoma
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 39
- 试验地点
- 4
- 主要终点
- Incidence of adverse events (AEs)
研究概览
简要总结
This phase I trial tests the safety, side effects, and best dose of camonsertib in combination with stereotactic body radiation therapy in controlling disease in patients with head and neck squamous cell cancer that has come back after a period of improvement (recurrent) or that cannot be removed by surgery (unresectable). Camonsertib may stop the growth of tumor cells and may kill them by blocking some of the enzymes needed for cell growth. Stereotactic body radiation therapy is a type of external radiation therapy that uses special equipment to position a patient and precisely deliver radiation to tumors in the body (except the brain). The total dose of radiation is divided into smaller doses given over several days. This type of radiation therapy helps spare normal tissue. Giving camonsertib in combination with stereotactic body radiation therapy may help control disease in patients with recurrent or unresectable head and neck squamous cell cancers.
详细描述
PRIMARY OBJECTIVES:
I. To evaluate the safety and tolerability of camonsertib with concurrent head and neck stereotactic body radiotherapy (SBRT) reirradiation for patients with recurrent head and neck squamous cell carcinoma (HNSCC).
II. To determine the recommended phase 2 dose (RP2D) of camonsertib in combination with concurrent SBRT in these patients.
SECONDARY OBJECTIVES:
I. To assess overall response rate within the radiation therapy field for patients treated with camonsertib and SBRT.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- •Patients must have histologically confirmed recurrent or metachronous (second primary) unresectable head and neck squamous cell carcinoma involving the oral cavity, oropharynx, larynx, hypopharynx, and/or paranasal sinus, or cervical lymphadenopathy with unknown primary. Core needle biopsy (preferably at least three 18-gauge cores) or incisional biopsy is preferred over fine needle aspiration (FNA) for diagnosis of recurrent disease or new primary head and neck squamous cell carcinoma to provide sufficient tumor tissue for correlative studies. Unresectable refers both to patients who have declined surgery and patients deemed unresectable by otolaryngology. This includes patients for whom curative resection is medically contraindicated and/or would be associated with excessive surgical risk (as deemed by the consulting otolaryngologist) or undue surgical morbidity (e.g., total glossectomy, laryngectomy, and/or major resection requiring free flap reconstruction). There are no requirements related to prior systemic therapies that patients may have received
- •Patients must have recurrent disease within a previously irradiated area (radiotherapy to dose ≥ 30 gray [Gy] and ≤ 80 Gy; in-field recurrence)
- •Patients must have completed prior radiotherapy at least 6 months prior to enrollment. Due to safety concerns, reirradiation within less than 6 months to the head and neck is very rarely recommended per standard of care
- •Patients must have measurable disease (at least one measurable lesion) as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.
- •Baseline imaging must include neck CT (preferably contrast-enhanced) and chest CT or skullbase to midthigh PET/CT (preferably with contrast-enhanced neck CT if diagnostic contrast-enhanced neck CT not available). Patients who have undergone surgery aside from biopsy may be included if gross disease is present within the surgical resection bed or at another site
- •Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of camonsertib in combination with radiotherapy in patients < 18 years of age, children are excluded from this study
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%)
- •Leukocyte count ≥ 3,000/mcL
- •Absolute neutrophil count ≥ 1,500/mcL
- •Platelets ≥ 100,000/mcL
- •Hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L without transfusion or erythropoietin dependency (within 7 days of assessment)
- •Serum bilirubin ≤ 1.5 × institutional upper limit of normal (ULN) (if total serum bilirubin > 1.5 × institutional ULN, then direct bilirubin must be < ULN)
- •Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) ≤ 3 × institutional ULN
- •Albumin > 2.5 mg/dL
- •Glomerular filtration rate (GFR) ≥ 60 mL/min/1.73 m^2
- •GFR can be measured directly or estimated using the site's institutional standards
- •Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
- •For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
- •Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
- •Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
- •Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class II or better
- •Ability to take pills by mouth
- •The effects of camonsertib on the developing human fetus are unknown. For this reason and because ATR inhibitors and radiation are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 6 months after completion of camonsertib administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
- •Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants
排除标准
- •Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > grade 1), with the exception of alopecia
- •Patients who are receiving any other investigational agents for a current cancer diagnosis
- •Patients with distant metastatic disease
- •Patients who have received more than one prior course of head and neck radiotherapy overlapping the region to be treated with the current diagnosis of head and neck cancer
- •Patients who have disease surrounding > 180 degrees of the carotid artery
- •Patients with tumors invading the mandible or tumors with gross skin involvement (i.e., tumor ulceration through the skin)
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to camonsertib or radiation
- •Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make participation in this protocol unreasonably hazardous
- •Pregnant women are excluded from this study because camonsertib is an ATR inhibitor with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with camonsertib, breastfeeding should be discontinued if the mother is treated with camonsertib. These potential risks may also apply to other agents used in this study
- •Patients diagnosed with scleroderma
- •Concomitant use of strong CYP3A4/5 inhibitors and inducers, and strong P-gp and BCRP inhibitors
- •Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
研究组 & 干预措施
Treatment (camonsertib, SBRT)
Patients undergo 4 or 5 treatment fractions of SBRT twice weekly, 2-3 days apart between fractions, over 3 weeks. Patients receive camonsertib PO QD on the day of and the day after each radiation therapy treatment. Patients also undergo PET/CT or CT and collection of blood samples throughout the trial.
干预措施: Biospecimen Collection (Procedure)
Treatment (camonsertib, SBRT)
Patients undergo 4 or 5 treatment fractions of SBRT twice weekly, 2-3 days apart between fractions, over 3 weeks. Patients receive camonsertib PO QD on the day of and the day after each radiation therapy treatment. Patients also undergo PET/CT or CT and collection of blood samples throughout the trial.
干预措施: Positron Emission Tomography (Procedure)
Treatment (camonsertib, SBRT)
Patients undergo 4 or 5 treatment fractions of SBRT twice weekly, 2-3 days apart between fractions, over 3 weeks. Patients receive camonsertib PO QD on the day of and the day after each radiation therapy treatment. Patients also undergo PET/CT or CT and collection of blood samples throughout the trial.
干预措施: Camonsertib (Drug)
Treatment (camonsertib, SBRT)
Patients undergo 4 or 5 treatment fractions of SBRT twice weekly, 2-3 days apart between fractions, over 3 weeks. Patients receive camonsertib PO QD on the day of and the day after each radiation therapy treatment. Patients also undergo PET/CT or CT and collection of blood samples throughout the trial.
干预措施: Computed Tomography (Procedure)
Treatment (camonsertib, SBRT)
Patients undergo 4 or 5 treatment fractions of SBRT twice weekly, 2-3 days apart between fractions, over 3 weeks. Patients receive camonsertib PO QD on the day of and the day after each radiation therapy treatment. Patients also undergo PET/CT or CT and collection of blood samples throughout the trial.
干预措施: Stereotactic Body Radiation Therapy (Radiation)
结局指标
主要结局
Incidence of adverse events (AEs)
时间窗: During dose escalation phase
The safety and tolerability of camonsertib will be evaluated during the dose escalation phase. The frequency and percentage of AEs will be provided overall and by dose level for any grade and attribution as well as for grade 3 or greater AEs, at least possibly related to treatment.
Maximum tolerated dose (MTD) of camonsertib and concurrent stereotactic body radiation therapy (SBRT) reirradiation
时间窗: During dose escalation phase
The dose-escalation phase will utilize a Bayesian Optimal Interval Design to determine the MTD for combined camonsertib and SBRT.
Incidence of late toxicities (dose expansion phase)
时间窗: Within 1 year of treatment initiation
The proportions of total patients experiencing late toxicities will be estimated. The frequency and percentage of AEs will be provided overall and by dose level for any grade and attribution as well as for grade 3 or greater AEs, at least possibly related to treatment.
次要结局
- Overall response rate(Up to 55 weeks)
- Progression-free survival (PFS)(From the start of treatment regimen until documented local or distal failure or death from any cause, assessed up to 55 weeks)