CTRI/2022/12/048448招募中3 期
A Phase 3 (Pivotal Stage) Study of NBTXR3 Activated by Investigator’s Choice of Radiotherapy Alone or Radiotherapy in Combination with Cetuximab for Platinum-based Chemotherapy-ineligible Elderly Patients with Locally Advanced Head & Neck Squamous Cell Carcinoma
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 500
- 试验地点
- 6
- 主要终点
- Progression-free Survival (PFS)
研究概览
简要总结
This is a global, open-label, randomized, 2-arm, Investigator’s choice Phase 3 (Pivotal Stage) study to investigate the efficacy/performance and safety of NBTXR3/RT±cetuximab versus RT±cetuximab in treatment-naïve, platinum-ineligible, elderly participants with LA-HNSCC.
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Open Label
入排标准
- 年龄范围
- 65.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- All
入选标准
- •Signed informed consent form (ICF) indicating that the subject understands the purpose of, and procedures required for the study, and is willing to participate in the study.
- •Biopsy-confirmed SCC of the oral cavity, oropharynx, hypopharynx, or supraglottic larynx (archived biopsies are allowed); if no biopsies are available, a new biopsy must be obtained to provide confirmation of SCC 3) For subjects with oropharyngeal cancer, HPV status must be known 4) Tumor categories T3-T4 according to the 8th edition of the American Joint Committee on Cancer Staging Manual (AJCC v8) 5) Has at least 1 tumor lesion that can be accurately measured according to RECIST 1.1 (per the central imaging vendor) and is amenable for intratumoral injection, as determined by the Investigator.
- •A single invaded, biopsy-confirmed, accessible LN in the neck of ≥3 cm and <10 cm and with <180-degree encasement of the carotid artery on MRI or CT scan is eligible for intranodal injection If a LN is selected for injection, 1 of the 2 injected lesions must be the primary tumor itself.
- •Ineligible to receive platinum-based chemotherapy for the treatment of LA-HNSCC as defined by having at least 1 of the following: a) Estimated creatinine clearance ≥30 and <50 mL/min (calculated by Cockcroft and Gault) b) Hearing loss or tinnitus Grade ≥2 c) Grade ≥2 peripheral neuropathy d) ECOG >2 e) Recent cardiac dysfunction (history of unstable angina pectoris, myocardial infarction, or New York Heart Association (NYHA) Class III chronic heart failure <3 years prior to screening) 7) Must be able to tolerate RT with curative intent as determined by the study Investigator 8) Amenable to definitive treatment with RT.
- •For subjects with an oral cavity cancer, the decision for definitive treatment with RT requires consultation with the head and neck surgeon and the site’s multidisciplinary tumor board 9) ECOG performance status of 0 to ≤2 10) Life expectancy ≥6 months 11) Adequate organ and bone marrow function at screening as defined by: a) Hemoglobin >9.0 g/dL b) Platelet count >100,000 cells/mm3 c) Leukocytes >3000 cells/mm3 d) Absolute neutrophil count >1500 cells/mm3 e) ALT ≤3 x upper limit of normal (ULN) f) AST ≤3 x ULN g) Total bilirubin ≤1.5 mg/dL (in subjects with Gilbert’s syndrome, if total bilirubin is >1.5×ULN, measure direct and indirect bilirubin and if direct bilirubin is ≤1.5×ULN, the subject may be eligible) h) Total serum magnesium within normal ranges (1.7-2.2 mg/dL or 0.85 to 1.10 mmol/L) Screening laboratory assessments will be performed by a central laboratory.
排除标准
- •HNSCC category T1, T2, or M1 according to AJCC v8 2) Has received prior antineoplastic systemic therapy or intervention (including pharmacological – both marketed and investigational, RT, or surgery) for the treatment of HNSCC 3) Subjects with known severe Grade 3 or 4 hypersensitivity reactions to cetuximab must be excluded from cetuximab treatment by the Investigator 4) Known history of HIV, active hepatitis B, or active hepatitis C infection 5) Local regionally recurrent HNSCC 6) Ulceration or other characteristics that may, in the opinion of the Investigator, increase the risk of severe tumor bleeding 7) SCC originating in the nasopharynx or paranasal sinus, salivary gland, or thyroid gland, or non-squamous histology (e.g., melanoma or neuroendocrine carcinoma), or SCC of unknown primary origin 8) Prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen 9) Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes, second- or third-degree atrioventricular heart block without a permanent pacemaker in place) 10) Class IV congestive heart failure as defined by the NYHA functional classification system <6 months prior to screening 11) A pregnant or nursing woman, or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception starting from the time that the ICF is signed through 150 days after the last cetuximab dose/RT fraction.
- •A woman who is 2 years postmenopausal or surgically sterile is not considered to be of childbearing potential 12) A known history of areca nut (betel nut) consumption for 10 years or more 13) Any condition that, in the opinion of the Investigator, participation would not be in the best interest of the individual (e.g., compromises the subject’s well-being) or that could prevent, limit, or confound the protocol/CIP-specified assessments 14) Subject participating in another clinical study, except for a non-interventional trial/registry, at the time of signing the ICF.
结局指标
主要结局
Progression-free Survival (PFS)
时间窗: time from randomization to | local-regional recurrence, local-regional | progression, distant progression, or death | from any cause, whichever occurs first
次要结局
- tumor response to NBTXR3 / RT ± cetuximab versus RT ± cetuximab(1) Objective Response Rate (as defined by the RECIST 1.1) rate of CR and partial response)
- Overall Survival (OS)(time from randomization to death from any cause)
- local-regional control of NBTXR3 / RT ± cetuximab versus RT ± cetuximab(Time from randomization to local-regional progression or death, whichever occurs first)
- Distant control of NBTXR3 / RT ± cetuximab versus RT ± cetuximab(Time from randomization to distant progression or death whichever occurs first)
- Cancer-specific survival(time from randomization to cancer-related death)
- Quality of Life over time - QLQ H and N35(Change from baseline over time in symptoms, function, and health related QOL using the European Organisation for Research and Treatment of Cancer (EORTC) questionnaire Head and Neck Cancer Module (QLQ H and N35))
- Quality of Life over time - EQ 5D 5L(Change from baseline over time in symptoms, function, and health related QOL using the 5 level EuroQol 5 dimension (EQ 5D 5L) instrument)
- Cancer-specific event-free survival(time from randomization to local-regional recurrence, local-regional progression, distant progression, or cancer-related death, whichever occurs first)
研究者
研究点 (6)
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