NCT05251389招募中1 期
Conversion of Unresponsiveness to Immunotherapy by Fecal Microbiota Transplantation in Patients With Metastatic Melanoma: a Randomized Phase Ib/IIa Trial
适应症
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 24
- 试验地点
- 2
- 主要终点
- Efficacy, defined as clinical benefit (stable disease (SD), partial response (PR), complete response (CR)
研究概览
简要总结
In this study the aim is to investigate whether transfer of the microbiota of either responder or non-responder patients via fecal microbiotica transplantation (FMT) can convert the response to immunotherapy in immune checkpoint inhibitors (ICI) refractory metastatic melanoma patients.
This is a randomized double-blind intervention phase Ib/IIa trial in ICI refractory metastatic melanoma patients receiving either FMT of an ICI responding or FMT from an ICI non-responding donor, in combination with ICI.
Following randomization, patients will receive vancomycin 250 mg, four times daily for 4 days (day -5 up until day -2), and undergo bowel clearance on day -1 (in total 1L MoviPrep). The FMT, either derived from donor group R (who showed a good response on anti-PD-1 therapy) or donor group NR (who showed progression on anti-PD-1 therapy), will be performed by a gastroenterologist using esophagogastroduodenoscopy. A total amount of 198mL (containing a total of 60 gram feces) will be used for transplantation. Anti-PD-1 treatment will be continued according to the patient's regular treatment schedule. Evaluation of safety and response to treatment will be performed.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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 should be 18 years or older
- •Patients have pathologically confirmed advanced stage cutaneous melanoma (stage III or IV) requiring systemic treatment with anti-PD-1
- •In case of stage IV disease, only patients with M1a or M1b disease are eligible.
- •Patients have confirmed disease progression (≥20% increase according to RECIST1.1) on two consecutive scans with a four week interval while on anti-PD-1 treatment, of which the second scan has to be performed within 3 weeks prior to signing informed consent.
- •Patients must have measurable disease per RECIST 1.1 criteria
- •Patients have an ECOG performance status of 0-1 (appendix D)
- •Patients have a life expectancy of >3 months
- •Patients have adequate organ function as determined by standard-of-care pre-checkpoint inhibitor infusion lab (including serum ALAT/ASAT less than three times the upper limit of normal (ULN); serum creatinine clearance 50ml/min or higher; total bilirubin less than or equal to 20 micromol/L, except in patients with Gilbert's Syndrome who must have a total bilirubin less than 50 micromol/L)
- •Patients have an LDH level of ≤1 times ULN
- •Patients of both genders must be willing to use a highly effective method of birth control during treatment
- •Patients must be able to understand and sign the Informed Consent document
排除标准
- •Patients with acral, uveal or mucosal melanoma, or patients with an unknown primary
- •Patients who have received treatment for their melanoma other than anti-PD-1 treatment.
- •Stage IV patients with M1c or M1d disease.
- •Patients with autoimmune diseases: patients with a history of inflammatory bowel disease, including ulcerative colitis and Crohn's disease, are excluded from this study (except Hashimoto thyroiditis, vitiligo, history of psoriasis, but no active disease)
- •Patients with any grade 3 or 4 immune-related adverse events still requiring active immunosuppressive medication, apart from endocrinopathies that are stable under hormone replacement therapy. Patients who had developed grade 3-4 immune related toxicity, which has reverted to grade I with immunosuppressive drugs and who are off immunosuppression at least two weeks prior to enrollment are eligible
- •Patients with brain or LM metastasis.
- •Patients with an elevated LDH level
- •Patients that have undergone major gastric/esophageal/bowel surgery (like Wipple, subtotal colectomy)
- •Severe food allergy (e.g. nuts, shellfish)
- •Patients with a swallowing disorder or expected bowel passage problems (ileus, fistulas, perforation)
- •Severe dysphagia with incapability of swallowing 2 liters of bowel lavage
- •Patients with a life expectancy of less than three months
- •Patients with severe cardiac or pulmonary comorbidities (per judgement of the investigator)
- •Women who are pregnant or breastfeeding
- •Patients with any active systemic infections, coagulation disorders or other active major medical illnesses
- •Patients with other malignancies, except adequately treated and a cancer-related life-expectancy of more than 5 years
- •Patients who received treatment with antibiotics in the three months prior to study enrolment, or patients we are expected to receive systemic antibiotics during the course of this study
结局指标
主要结局
Efficacy, defined as clinical benefit (stable disease (SD), partial response (PR), complete response (CR)
时间窗: At 12 weeks after FMT
次要结局
- Safety, measured as the occurrence of toxicity of grade 3 or higher(At screening, and 2 weeks, 6 weeks, 12 weeks and 16 weeks after FMT)
- Progression free survival (PFS)(Up to one year post-FMT)
- The change in gut microbiome following FMT and the duration and stability over time(At screening, and 2 weeks, 6 weeks, 12 weeks and 16 weeks after FMT)
- The change in metabolome following FMT and the duration and stability over time(At screening, and 2 weeks, 6 weeks, 12 weeks and 16 weeks after FMT)
- The immune changes; changes in cell populations (absolute, relative, phenotypical), in chemokine/cytokine levels and in the tumor-microenvironment(At screening, and 2 weeks, 6 weeks, 12 weeks and 16 weeks after FMT)
研究者
研究点 (2)
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