Anti PD-1 Plus Postbiotic Versus Anti PD-1 Alone in Locally Advanced or Metastatic, Treatment naïve, Cutaneous Melanoma: a Phase II Randomized Study With Correlative Biomarkers' Analysis:
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 35
- 试验地点
- 5
- 主要终点
- Biological response rate
研究概览
简要总结
The association between microbiota and response to ICI-based therapy reflects the ability of bacterial metabolites to upregulate MHC class I APM component expression and/or function in cancer cells, leading to their elimination by the host's immune system.
Thus, the aim of this project is to evaluate the ability of anti PD-1 combined with postbiotic, that here will be a coadjuvant of a standard immunotherapy to upregulate MHC class I APM component expression and/or function in cancer cells compared to anti PD-1 alone in first line advanced melanoma patients.
详细描述
The study is designed for the primary endpoint as a non-comparative calibrated phase II clinical trial. Patients assigned to the anti PD-1 alone arm will be considered as the calibration group. . Results obtained in the calibration arm will be used to judge the results obtained in the experimental arm.
This is a study protocol settled up on a biological primary endpoint To evaluate the activity of the combination of anti PD-1 plus postbiotic in terms of upregulation of MHC class I APM component expression and/or function in advanced, treatment naïve, cutaneous melanoma patients. The Clinical Objectives is to evaluate the activity of the combination of anti PD-1 plus postbiotic compared to anti PD-1 alone in terms of overall response rate (ORR).
To evaluate the efficacy of the combination of anti PD-1 plus postbiotic compared to anti PD-1 alone in terms of PFS.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 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
- •Patients 18 years or older
- •Histologically confirmed, unresectable stage IIIC or IV metastatic melanoma;
- •Eastern Cooperative Oncology Group performance status of 0 or 1;
- •The patient must treatment naïve for metastatic disease
- •Patients who have received anti-PD-1 therapy or anti BRAF/MEK in adjuvant setting and relapsed after 6 months of ending adjuvant therapy are allowed to enter clinical study.
- •Patient has at least one measurable lesion that qualifies as a target lesion based on RECIST 1.
- •Tumor lesions situated in a previously irradiated area, or in an area subjected to other loco-regional therapy, are not considered measurable unless there has been demonstrated progression in the lesion.
- •Patient is willing to undergo a pretreatment tumor biopsy or provide qualifying archival tumor tissue. To qualify, archival tissue must have been sampled after last exposure to any systemic anti-neoplastic agent (including TVEC or anti-PD-L1 therapy whichever is last). Patients unable to undergo a biopsy may be enrolled if risk/benefit ratio of biopsy is considered unfavorable and/or when a biopsy would likely lead to significant delays in care. This decision must be accompanied by supporting documentation from the Investigator and performed in consultation with Medical Monitor. All pretreatment tissue must have been collected no more than 120 days prior to screening.
- •Patient has recovered from the effects of any previous chemotherapy, immunotherapy, other prior systemic anticancer therapy, radiotherapy, and/or surgery (ie, residual toxicity no worse than Grade 1 [Grade 2 treatment-associated peripheral neuropathy and/or any grade of alopecia are acceptable assuming all other inclusion criteria are met]).
- •Patient who has received prior systemic anti-neoplastic agent(s) must wait at least 5 half-lives or 4 weeks (whichever is shorter) following prior therapy before enrollment into the study, or 4 weeks if the half-life of a given investigational agent is not known.
- •Patient has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1 within 5 days before the first dose of study drug and an estimated life expectancy of at least 3 months.
- •Patient has adequate hematologic reserve as evidenced by:
- •Absolute neutrophil count (ANC) of ≥1000/μL, Absolute lymphocyte count of
- •≥500/μL, Platelet count of ≥75,000/μL, and Hemoglobin of ≥9 g/dL (patients may be transfused to this level, if necessary, but transfusion must occur >1 week prior to the first dose of study drug).
- •Patient has adequate hepatic function as evidenced by aspartate transaminase and alanine transaminase values ≤3 × the upper limit of normal (ULN) and serum total bilirubin values of ≤1.5 × ULN (≤2 × ULN for patients with known Gilbert's syndrome) for the reference laboratory measured within 7 days prior to the first dose of study drug. For patients with documented baseline liver metastasis, the following limits will apply: 5 × ULN for transaminase and 2 × ULN for bilirubin.
- •Patient has adequate renal function as evidenced by a serum creatinine ≤1.5 × the ULN for the reference laboratory or a calculated creatinine clearance of ≥45 mL/min by the Cockcroft-Gault Equation measured within 7 days prior to the first dose of study drug.
- •Patient has international normalized ratio (INR) AND/OR prothrombin time (PT) AND activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless the patient is receiving anticoagulant therapy, in which case INR and/or PT and aPTT must be within the desired therapeutic range of intended use for such anticoagulants.
- •Patient agrees to abide by the contraceptive requirements detailed in the protocol.
- •Women of childbearing potential (WOCBP) must have a negative pregnancy test (serum or urine) within 3 days before the first dose of study drug (see the protocol for the definition of WOCBP).
- •Life expectancy more than 3 months
- •Presence of instrumentally or clinically measurable or evaluable lesions Informed consent obtained
排除标准
- •Patients with mucosal or with a primary ocular melanoma
- •Active symptomatic or asymptomatic brain metastases
- •Patients with the following disorders: active, known, or suspected autoimmune disease (except for some non-serious disorders, such as vitiligo and type 1 diabetes mellitus, as specified in the study protocol);
- •Previous malignancies (exceptions skin basocellular or squamocellular carcinoma radically resected, in situ uterine cervix in situ carcinoma radically resected) in the previous 2 years.
研究组 & 干预措施
Postbiotic+AntiPD1
patient will be treated with the postbiotic agent and AntiPD1 choose as for standard practice
干预措施: Postbiotic (Dietary Supplement)
Postbiotic+AntiPD1
patient will be treated with the postbiotic agent and AntiPD1 choose as for standard practice
干预措施: AntiPD1 (Drug)
AntiPD1
patient will be treated with AntiPD1 as per clinical standard practice
干预措施: AntiPD1 (Drug)
结局指标
主要结局
Biological response rate
时间窗: 18 months
proportion of responder patients at 12 weeks from treatment start. The response to treatment is based on the IHC level of HLA and NRLC5 at baseline and after 12 weeks from treatment start. An IHC level equal to 0 or 1+ is defined as low, while a IHC value equal to 2+ or 3+ is defined as high
次要结局
- Objective Response Rate(18 months)
研究者
Mario Mandalà
Director of Department
Azienda Ospedaliera di Perugia