2024-517565-16-00招募中2 期
A Phase II, Open-Label, Single-Arm, Multicentre Study of Carboplatin, Paclitaxel, and Tislelizumab in Biomarker-Selected Patients with Resectable Locally Advanced Oral Cavity Squamous Cell Carcinoma - PERSEPHONE Trial
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 28
- 试验地点
- 6
- 主要终点
- Activity: rate of Major Pathological Response (MPR, i.e. less than 10% viable tumour cells identified on routine haematoxylin and eosin staining in pathological surgical specimen) in patients with locally advanced oral cavity squamous cell carcinoma treated with tislelizumab + carboplatin + paclitaxel in the neoadjuvant setting.
研究概览
简要总结
To evaluate the anti-tumor activity of the study combination in locally advanced oral cavity squamous cell carcinoma.
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 是
入选标准
- •Patients of both genders, aged ≥18 years
- •Patient has adequate organ and marrow function (absolute neutrophil count ≥ 1500, haemoglobin ≥ 9.0 gram/decilitre (g/dL), platelet count ≥ 100,000, total bilirubin ≤1.5 times institution's upper limit of normal, AST/SGOT and ALT/SPGT ≤ 2.5 times institutional upper limit of normal, albumin ≥ 2.0 g/dL, serum creatinine ≤ 1.5 times institutional upper limit of normal or creatinine clearance ≥ 60 millilitres per minute (mL/min) according to Cockroft-Gault formula, or local institutional standard method)
- •Participant must agree to not donate blood during the study or for 90 days after the last dose of study treatment
- •Women of childbearing potential (according to recommendations of the Clinical Trial Facilitation Group) must have a negative serum pregnancy test at screening and must not be breastfeeding.
- •Women of childbearing potential must agree to use highly effective contraceptive method(s) from ICF signature to 6 months after the last dose of study treatment, whichever is the latest. See Section 5.4 for a list of acceptable birth control methods.
- •Non-sterilized males who are sexually active with a female partner of childbearing potential must agree to use condom and spermicide from ICF signature to 6 months after the last dose of study treatment, whichever is the latest. Because male condom and spermicide is not a highly effective contraception method, it is required that female partners of a male study subject use highly effective contraceptive method(s) throughout this period.
- •Male subjects must refrain from donating sperm during the clinical study and for 6 months after the last dose of study treatment, whichever is the latest. If not done previously, cryopreservation of sperm prior to receiving chemotherapy + tislelizumab is advised to male patients with a desire to have children.
- •Participant must be able to understand the study procedures and agree to participate in the study by providing written informed consent.
- •Willing and able to sign written informed consent prior to study screening
- •Histologically confirmed, squamous cell carcinoma of the oral cavity
- •Disease amenable for local surgery with curative intent
- •Stage III-IV(M0) according to the VIII edition of AJCC staging system
- •Biomolecular inclusion criteria: CPS PDL-1 > 1 tumours and CD8+/FOXP3+ ratio equal or higher than
- •PD-L1 status will be assessed by VENTANA PD-L1 assay and/or 22C3pharmDX. In tumour biopsies performed multiplex-immunofluorescence (mIF) will analyse CD8+/FOXP3+ ratio. The analysis will be carried out by a central laboratory
- •Performance status ECOG 0-1
- •Availability of tumour tissue via biopsy and provided for study purposes. Needle or resected tissue is required; cytological specimens such as fine needle aspirated or cell block are not acceptable
- •Willing to provide blood samples for study purposes
排除标准
- •Patient has recurrent/metastatic disease
- •Participant must not have a serious, uncontrolled medical disorder, non-malignant systemic disease, or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 90 days) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, hypertension (defined as systolic blood pressure >140 mmHg or diastolic blood pressure > 90 mmHg) that has not been adequately controlled or treated; prior history of posterior reversible encephalopathy syndrome, or any psychiatric disorder that prohibits obtaining informed consent
- •Participant must not have known, symptomatic brain or leptomeningeal metastases
- •Participant has a diagnosis of immunodeficiency or has received systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to initiating protocol therapy
- •Any concurrent chemotherapy, Investigational Product, biologic, or hormonal therapy for cancer treatment
- •Subjects with previous malignancies (except non-melanoma skin cancers, and the following in situ cancers: bladder, gastric, oesophageal, colon, endometrial, cervical/dysplasia, melanoma, or breast) unless a complete remission was achieved at least 2 years prior to study entry AND no additional therapy is required during the study period
- •Subjects with an active, known or suspected autoimmune disease. Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enrol
- •Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of enrolment. Inhaled or topical steroids, and adrenal replacement steroid > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease
- •Subjects with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity
- •Known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the trial
- •Known active Hepatitis B infection (defined as presence of HBsAg and/or HBV DNA), active hepatitis C infection (defined as positive HCV RNA), unless it is under stable treatment and/or with undetectable viral load and/or known Human Immunodeficiency Virus (HIV). Patients with HIV who have a normal CD4 count (≥ 200) and an undetectable viral load are not excluded
- •Patient with locally advanced disease not amenable of surgery with curative intent
- •Pregnant or breast-feeding patients. Women of childbearing potential must have a negative pregnancy test performed within 72 hours before treatment start. Both men and women enrolled in this trial must use adequate barrier birth control measures during the course of the trial and 6 months after the last dose of study treatment
- •Known medical condition that, in the investigator’s opinion, would increase the risk associated with study participation or study drug administration or interfere with the interpretation of safety results
- •History or current evidence of any condition that, in the opinion of the treating investigator, might interfere with the subject's participation for the full duration of the trial
- •Participant has received a live vaccine within 14 days of initiating protocol therapy.
- •Patient has received prior local or systemic treatment for HNSCC
- •Patient must not be simultaneously enrolled in an interventional clinical trial
- •Patient must not have had major surgery ≤3 weeks prior to initiating protocol therapy and patient must have recovered from any surgical effects
- •Participant must not have received investigational therapy ≤ 4 weeks, or within a time interval less than at least 5 half-lives of the investigational agent, whichever is longer, prior initiating protocol therapy
- •Participant has had radiation therapy encompassing >20% of the bone marrow within 2 weeks; or any radiation therapy within 1 week prior to Day 1 of protocol therapy
- •Participant must not have a known allergy to tislelizumab, paclitaxel or carboplatin components or excipients
- •Participant must not have received a transfusion (platelets or red blood cells) ≤ 4 weeks prior to initiating protocol therapy
结局指标
主要结局
Activity: rate of Major Pathological Response (MPR, i.e. less than 10% viable tumour cells identified on routine haematoxylin and eosin staining in pathological surgical specimen) in patients with locally advanced oral cavity squamous cell carcinoma treated with tislelizumab + carboplatin + paclitaxel in the neoadjuvant setting.
Activity: rate of Major Pathological Response (MPR, i.e. less than 10% viable tumour cells identified on routine haematoxylin and eosin staining in pathological surgical specimen) in patients with locally advanced oral cavity squamous cell carcinoma treated with tislelizumab + carboplatin + paclitaxel in the neoadjuvant setting.
次要结局
- Safety: Number of adverse events and percentages, stratified for grade, of the neoadjuvant treatment with tislelizumab + carboplatin + paclitaxel measured by Common Terminology Criteria for Adverse Events (CTCAE) v 5.0.
- Survival a) 3-year overall survival (OS); b) 3-year disease free survival (DFS), defined as the time from treatment assignment to cancer recurrence, second cancer or death from any cause.
- Exploratory endpoint: To evaluate longitudinal modification in circulating-DNA (ctDNA) and immune infiltrates in tumour samples and to correlate them with pathological response after neoadjuvant therapy;
- Exploratory endpoint: Identification, quantification and correlation of specific biomarkers (e.g., protein expression patterns, immune cell phenotypes) associated with treatment response, measured via IMC in pre-treatment and post-treatment tissue samples
- Exploratory endpoint: Overall survival (OS), progression-free survival (PFS) and longitudinal ctDNA levels evaluated in the subgroup of patients who lack bio-molecular eligibility but meet other clinical criteria.
研究者
Paolo Bossi
Scientific
Gruppo Oncologico Del Nord Ovest
研究点 (6)
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