Efficacy and Safety Evaluation of VS-101 in Combination With Chemoradiotherapy in Patients With Head and Neck Cancer

Официальное название

A Multi-center, Randomized, Open-label, Parallel-group, Phase 2 Study to Evaluate the Efficacy and Safety of VS-101 in Combination With Chemoradiotherapy (CRT) in Patients With Head and Neck Cancer

Обзор

This will be a multi-center, randomized, open-label, parallel-group study in adult patients with head and neck cancer.

Вмешательства

• Препарат VS-101
  VS-101
• Препарат Cisplatin
  Cisplatin
• Лучевая терапия Radiation
  Radiation

Первичные конечные точки

• Objective response rate (ORR) [Срок оценки: 6 months and 12 months]

Вторичные конечные точки (9)

• Disease control rate (DCR) [Срок оценки: 6 months and 12 months]
• Best overall response (BOR) [Срок оценки: 6 months and 12 months]
• Progression-free survival (PFS) [Срок оценки: At 6 month and 1 year]
• Locoregional control (LRC) [Срок оценки: At 6 month and 1 year]
• Distant metastasis (DM) [Срок оценки: through study completion, at most 1 year]
• Overall survival (OS) [Срок оценки: 1 year]
• Changes in tumor size [Срок оценки: through study completion, at most 1 year]
• Number and severity of treatment-emergent adverse events (TEAEs), treatment-related AEs, and serious adverse events (SAEs) for all dose groups according to the NCICTCAE version 5.0 [Срок оценки: through study completion, at most of 1 year]
• Health-related quality of life (HR-QoL) [Срок оценки: at week1, week8, week11, week 19, week 27 and week 52]

Критерии участия

Критерии включения

• Males or females aged more than 18 years at the time of ICF signing
• Diagnosed based on position emission tomography (PET), computed tomography (CT), or magnetic resonance imaging (MRI) with pathologically confirmed (histologic or cytological) head and neck squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx
• Defined by American Joint Committee on Cancer \[AJCC\] Guidelines 8th Edition:

• Oral cavity, hypopharynx, or larynx (independent of p16): Stage III, IVa, IVb per TNM guidelines; or
• Oropharyngeal p16 negative disease: Stage III, IVa, IVb per TNM guidelines; or
• Oropharyngeal p16 positive disease: Stage III per TNM guidelines
• Have measurable disease based on RECIST 1.1
• Participants with head and neck cancer who have limited to those receiving definitive CRT without surgical excision
• Participants prescribed standard intensity-modulated radiation therapy (IMRT) with a cumulative planned dose of approximately 70 Gy
• Participants with Eastern Cooperative Oncology Group (ECOG) Performance Statue (PS) of 0 \~ 2
• Participants with the status of National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI CTCAE) version 6.0 Grade 2 if stable and not clinically significant, or lower for acute or chronic adverse reaction at the time of screening
• Participants with an expected survival period of at least 20 weeks
• Participants who can comply with the requirements of the clinical trial protocol
• Ability to understand and willingness to sign a written informed consent document

Критерии исключения

• Medical History

• Patients with a history of prior radiation to the head and neck region which overlap with the planned radiation fields (or cumulative doses exceed the constraints for organs-at-risk \[OAR\]) or with a known susceptibility to radiation.
• Patients with active or uncontrolled or clinically significant medical or psychiatric disorders that, in the investigator's opinion, may interfere with informed consent, adherence, or patient safety. Stable medical or psychiatric conditions under a stable dose regimen are permitted.
• Patients with a history of uncontrolled seizure disorder. Patients with a remote history of a single provoked seizure or well-controlled seizures on stable monotherapy may be eligible.
• Patients who are unable to swallow the study tablet at the screening visit, unless a nasogastric (NG) tube or percutaneous endoscopic gastrostomy (PEG) tube is already in place for clinically indicated reasons and the patient is clinically stable.
• Patients who show abnormalities in the following test results at the time of screening:

• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2.5 × upper limit of normal (ULN)
• Creatine clearance ≤50 mL/min (using Cockcroft-Gault (C-G) formula)
• Absolute neutrophil count (ANC) <1,500/µL
• Platelets <100,000/µL
• Hemoglobin <9 g/dL
• Serum calcium >1.5 × ULN
• Total bilirubin > 2 × ULN
• Prothrombin time (PT) (International Normalized Ratio \[INR\]) >1.5 × ULN or activated partial thromboplastin time (aPTT) (sec)
• Positive result for serum tests (hepatitis B or C virus, human immunodeficiency virus \[HIV\], rapid plasma reagin \[RPR\] test)
• Patients who show significant abnormalities in electrocardiogram (ECG) test results (e.g.,QTcF > 450 msec)
• Patients who received hypofractionated chemoradiation regimens (> 2 Gy per day) Note：If it is established that the abnormal lab values are a consequence of their underlying malignant disease rather than any other co-existing condition, reflect minor variations attributable to individual differences or testing conditions, and is not considered clinically significant, the Principal Investigator (PI) may discuss the case with the Medical Monitor to determine eligibility.
• Patients with known hypersensitivity to components or excipients of clinical investigational drugs
• Participants with a history of drug addiction within 3 months before ICF signing, unless a Urine drug screen negative result is obtained prior to randomization
• Contraindicated Drugs and Treatments:

• Participants who have administered strong cytochrome P450 (CYP) 3A4 or CYP2D6 inducers or inhibitors within 14 days of baseline or 5 times the drug's half-life, whichever is longer.
• Participants who received chemotherapy within 14 days of baseline (drugs or treatment known to have anticancer effects such as cytotoxic chemotherapy, antihormonal therapy, and targeted therapy).
• Participants who required intravenous antibiotics, antivirals, or antifungals for active or uncontrolled infection at baseline.
• Participants who have administered benzodiazepines (e.g., lorazepam) that causes clinically significant sedation (stable low dose is permitted).
• Participants who participated in another clinical trial within 4 weeks of the baseline and administered the clinical trial drug
• Participants and their spouses (or partners) with childbearing potential who are not using medically acceptable methods of contraception for the duration of the trial and for 14 months (in female participants) and 11 months (in male participants) after the last dose of cisplatin treatment
• Participants who, in the judgment of other investigators, are not suitable to participate in the study"

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 2 центра

• Yale Cancer Center — New Haven
• NYU Langone Health — Manhattan

Идентификаторы

NCT: NCT06959082 · VS-101-C3

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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