A Phase II Study of Induction/Window of Opportunity Toripalimab Followed by Definitive Chemoradiotherapy (CRT) and Adjuvant Toripalimab for Patients With Locally Advanced Esophageal Squamous Cell Carcinoma (ESCC)
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- To determine the clinical complete response rate to proportion of patients with complete clinical response (cCR) 4-12 weeks after completion of standard-of-care (SOC) dCRT.
研究概览
简要总结
This is a phase 2/window of opportunity study to determine the efficacy, by clinical complete response, and safety of induction toripalimab (PD-1 inhibitor) followed by definitive chemoradiotherapy (dCRT) and adjuvant toripalimab (up to one year) in patients with stage II - IVA ESCC. Tumor biopsies (tumor tissue, adjacent normal tissue), blood including ctDNA, and saliva will be obtained before, during, and after the induction phase. These tissues will be assessed for clinical and research associated markers and processes that may provide information regarding the role of toripalimab in tumor related processes.
详细描述
Intravenous (IV) toripalimab infusions on Day 1 of each 21-day treatment cycle for 2 doses prior to dCRT followed by adjuvant toripalimab for up to 1 year. No toripalimab will be given during SOC dCRT.
After dCRT, all patients can progress to adjuvant toripalimab or resection followed by adjuvant toripalimab. After adjuvant toripalimab, routine surveillance will involve serial esophagogastroduodenoscopies (EGDs) and imaging.
Treatment will continue for up to an additional year with adjuvant toripalimab infusions, until disease progression, or intolerable toxicity. Patients will be followed for OS and subsequent anticancer therapy for up to 3 years after ending study treatment.
Note: Toripalimab will be provided to the study by Coherus. Each site will obtain carboplatin and paclitaxel from commercial supply to administer as standard of care.
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 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed and dated written informed consent.
- •Age ≥ 18 years the day of signing informed consent.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 -
- •Previously untreated, resectable, histologically confirmed stage II-IVA esophageal squamous cell carcinoma according to the 8th TNM staging system of the American Joint Committee on Cancer.
- •Has provided archival or newly obtained core or excisional biopsy tissue (fine needle aspirate [FNA] is not adequate) of a tumor lesion for local standard of care biomarker analysis. Repeat samples may be required if adequate tissue is not provided. Note: Formalin-fixed, paraffin embedded tissue blocks are preferred to slides.
- •Adequate organ and bone marrow function resulted ≤ 28 days prior to first dose of protocol-indicated treatment:
- •Absolute neutrophil count (ANC) ≥ 1500/µL.
- •Platelets ≥ 100,000/µL.
- •Hemoglobin ≥ 7.0 g/dL
- •Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min (as calculated by the Cockcroft-Gault Formula or calculated/measured by an alternative established institutional standard consistently applied across participants at the site) or serum creatinine ≤ 1.5x upper limit of normal (ULN)
- •Total bilirubin ≤ 1.5 times institutional ULN
- •AST (SGOT) and ALT (SGPT) ≤ 2.5 times institutional ULN.
- •Serum albumin ≥ 2.8 g/dL
排除标准
- •Locally advanced and incurable or metastatic disease is deemed incurable.
- •History of another malignancy within 3 years prior to screening, except for non-melanoma skin carcinoma, low-grade localized prostate cancer, superficial bladder cancer, ductal carcinoma in situ (CIS) of the breast, CIS of the cervix, or stage I uterine cancer.
- •Multiple primary esophageal cancers.
- •Previous radiotherapy of the thorax.
- •Previous immune checkpoint inhibitor therapy (including agents targeting PD-1, PD-L1/PD-L2, CTLA-4, LAG-3, TIGIT).
- •Active autoimmune disease, solid organ transplant recipient, or prednisone dose (or a steroid equivalent) of more than 10mg daily.
- •Previous non-infectious pneumonitis or interstitial lung disease.
- •Any severe comorbidity (e.g. uncontrolled diabetes or decompensated heart failure) which in the determination of the treating physician would preclude the patient from receiving this experimental treatment regimen.
- •Contraindication to ICI or suspected allergy/hypersensitivity to monoclonal antibodies or any ingredients of toripalimab.
- •Known allergy/hypersensitivity to carboplatin or paclitaxel.
- •Inability to provide informed consent due to psychological, familial, social, or other factors.
- •Presence of CTCAEv6 grade ≥ 2 neuropathy.
- •Pregnant or breastfeeding.
研究组 & 干预措施
Toripalimab + CRT
Intravenous (IV) toripalimab infusions on Day 1 of each 21-day treatment cycle for 2 doses prior to dCRT followed by adjuvant toripalimab for up to 1 year. No toripalimab will be given during SOC dCRT.
After dCRT, all patients can progress to adjuvant toripalimab or resection followed by adjuvant toripalimab. After adjuvant toripalimab, routine surveillance will involve serial esophagogastroduodenoscopies (EGDs) and imaging.
Treatment will continue for up to an additional year with adjuvant toripalimab infusions, until disease progression, or intolerable toxicity. Patients will be followed for OS and subsequent anticancer therapy for up to 3 years after ending study treatment.
Note: Toripalimab will be provided to the study by Coherus. Each site will obtain carboplatin and paclitaxel from commercial supply to administer as standard of care.
干预措施: Carboplatin + Paclitaxel (Drug)
Toripalimab + CRT
Intravenous (IV) toripalimab infusions on Day 1 of each 21-day treatment cycle for 2 doses prior to dCRT followed by adjuvant toripalimab for up to 1 year. No toripalimab will be given during SOC dCRT.
After dCRT, all patients can progress to adjuvant toripalimab or resection followed by adjuvant toripalimab. After adjuvant toripalimab, routine surveillance will involve serial esophagogastroduodenoscopies (EGDs) and imaging.
Treatment will continue for up to an additional year with adjuvant toripalimab infusions, until disease progression, or intolerable toxicity. Patients will be followed for OS and subsequent anticancer therapy for up to 3 years after ending study treatment.
Note: Toripalimab will be provided to the study by Coherus. Each site will obtain carboplatin and paclitaxel from commercial supply to administer as standard of care.
干预措施: Toripalimab (Drug)
结局指标
主要结局
To determine the clinical complete response rate to proportion of patients with complete clinical response (cCR) 4-12 weeks after completion of standard-of-care (SOC) dCRT.
时间窗: 4-11 weeks after completion of standard-of-care (SOC) dCRT.
Determine cCR score by achieving all of these:1 * No lesion, budding, or ulceration identified on esophagogastroduodenoscopy (EGD). * Bite-on-bite biopsies with no residual tumor. * EGD with endoscopic ultrasound (EUS) and fine needle aspiration (FNA) of suspicious lymph nodes (LNs) shows no residual tumor. If patients have suspicious LNs unable to be reached by FNA, they will not be classified as clinical complete responders.
次要结局
- To determine Disease-free survival (DFS(from start of treatment until 1, 2, and 3yrs post treatment)
- To determine Overall survival (OS)(from start of treatment until 2 and 3yrs post treatment)
- To determine frequency of Adverse Events (AEs)(through study completion, an average of 1 year)
- To determine Quality of life (QOL) measurements((during screening), after induction (post-induction assessment), after dCRT (post-CRT assessment), at EOT visit, and then at coinciding follow-up visits for up to 3 years)
研究者
Michael K. Gibson
Principal Investigator
Vanderbilt-Ingram Cancer Center