EPIC - A Phase 2, Randomized, Open-label, Multicenter, Controlled Study to Evaluate the Efficacy, Safety, and Tolerability of Extracorporeal Photopheresis (ECP) Versus Best Available Therapy (BAT) in Melanoma or Non-Small Cell Lung Cancer (NSCLC) Patients With Immune-related Colitis Induced by Immune Checkpoint Inhibitor Therapy Who Have Inadequate Response to Steroids
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Proportion of Participants with Remission of ir-colitis at End of Treatment
研究概览
简要总结
The photoactivating agent UVADEX (methoxsalen) is used in conjunction with extracorporeal photopheresis (ECP) as an immunomodulatory therapy approved for the treatment of cutaneous T-cell lymphoma. ECP involves collecting whole blood from the patient, separating white blood cells (WBCs) via centrifugation, combining them with UVADEX, and then exposing them to ultraviolet A (UVA) light. All blood components, including the treated WBCs, are then returned to the patient.
Immune Checkpoint inhibitor (ICI) therapy is used to treat different types of cancer, and one major side-effect of ICI therapy is immune-related colitis (ir-colitis). The main purpose of the study is to evaluate the efficacy of UVADEX in conjunction with ECP versus best available therapy (BAT) in participants with melanoma or NSCLC that suffer from ir-colitis with inadequate response to steroids.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Participants diagnosed with unresectable or metastatic melanoma or unresectable, advanced or metastatic NSCLC, who received ICI treatment with agents like anti-programmed death-1 (PD-1), anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4), and had shown a response to the treatment, based on having a complete response, partial response, or stable disease determined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.
- •Participants diagnosed with ir-colitis of at least Grade 2 severity based on American Society of Clinical Oncology (ASCO) Guidelines (diarrhea with an increase of ≥4 stools more than at baseline) with other causes of diarrhea and colitis ruled out.
- •Participants with endoscopy evidence of ir-colitis based on colonoscopy (modified Mayo Endoscopy Subscore of ≥2).
- •Participants with inadequate response to corticosteroids, defined as no improvement in ir-colitis after at least 72 hours of corticosteroid treatment, or relapse of ir-colitis during or after corticosteroid tapering.
- •Participants who have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Participants who may become pregnant must have a negative serum pregnancy test, agree to use effective birth control methods during the study and for 30 days after the last treatment, and not be breastfeeding.
- •Participants whose sexual partner may become pregnant, must use condoms or other effective contraception, and avoid donating blood, semen, or sperm during the study and for 90 days after the last treatment.
- •Participants must agree to wear UVA-absorbing, wrap-around sunglasses and cover exposed skin or use a sunblock (sun protection factor [SPF] ≥ 15) for the 24-hour period following treatment with UVADEX, whether exposed to direct or indirect sunlight.
排除标准
- •Presence of irAEs and other than ir-colitis, with severity grade > 2 based on ASCO guidelines.
- •Treatment of ir-colitis with any systemic therapy other than corticosteroids.
- •Concurrent conditions that might require treatment with corticosteroids ≥ 1 milligram per kilogram body weight per day (mg/kg BW/day) prednisone equivalent.
- •Concomitant treatment with any chemotherapy or targeted therapy for malignant melanoma, NSCLC, or other cancers.
- •Use of any investigational agent within 5 half-lives of the study treatment.
- •Contraindications to study interventions or procedures (UVADEX, the ECP procedure, infliximab, or vedolizumab).
- •Known allergic reaction to any component of the investigational agents, 8-methoxsalen (UVADEX), infliximab, or vedolizumab.
- •Presence of aphakia or history of light-sensitive diseases such as lupus erythematosus, porphyria cutanea tarda, erythropoietic protoporphyria, variegate porphyria, xeroderma pigmentosum, or albinism.
- •Inability to tolerate the fluid shift associated with the ECP procedure.
- •Positive test for human immunodeficiency virus (HIV).
- •Positive test for tuberculosis (blood test).
- •History of prior allogeneic bone marrow or solid organ transplantation.
- •Previous or current malignancies within the last 3 years, other than unresectable or metastatic melanoma or unresectable, advanced, or metastatic NSCLC treated with ICI. Exceptions include adequately treated basal or squamous cell skin cancer.
- •Note: Other Inclusion/Exclusion criteria also apply.
研究组 & 干预措施
UVADEX in conjunction with extracorporeal photopheresis
Participants will receive UVADEX, in conjunction with ECP procedure twice weekly for four weeks and then every other week for 8 weeks during the 12-week treatment period according to the treatment schedule.
干预措施: Methoxsalen (Drug)
Best available therapy (BAT)
Participants will receive either infliximab or vedolizumab as per the investigator's choice during the 12-week treatment period.
干预措施: Infliximab (Drug)
Best available therapy (BAT)
Participants will receive either infliximab or vedolizumab as per the investigator's choice during the 12-week treatment period.
干预措施: Vedolizumab (Drug)
结局指标
主要结局
Proportion of Participants with Remission of ir-colitis at End of Treatment
时间窗: Week 12 (diarrhea frequency) / Week 13 (colonic mucosal endoscopy score)
Composite endpoint of remission measured by diarrhea frequency (CTCAE grade 0 or 1 at Week 12) and colonic mucosal endoscopy score (modified Mayo Score 0 or 1 at Week 13).
次要结局
- Total Duration of Remission for ir-colitis Based on the Criteria for Diarrhea(Week 64)
- Proportion of Participants with Complete Resolution of Diarrhea(Week 12)
- Proportion of Participants with Complete Resolution of Colonic Endoscopic Changes(Week 13)
- Proportion of Participants with Corticosteroid-free Clinical Remission(Week 12)
- Changes in the Nancy Score(Week 13)
- Proportion of Participants with Stool Calprotectin Level <150 micrograms per gram (μg/g)(Week 26)
- Proportion of Participants with Complete Resolution of Other Symptoms of ir-colitis(Week 64)
- Time to Complete Resolution of ir-colitis Based on Common Terminology Criteria for Adverse Events (CTCAE) Criteria for Colitis(Week 64)
- Time to Complete Resolution of Other Specified Immune-related Adverse Events (irAEs) (other than ir-colitis)(Week 64)
- Time to Complete Discontinuation of Systemic Corticosteroids for at least 1 Week(Week 12)
- Progression Free Survival (PFS) for Melanoma and NSCLC(Week 64)
- Overall Survival (OS)(Week 64)