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Fecal Microbial Transplantation in Combination With Immunotherapy in Melanoma Patients (MIMic)

Immunotherapy has helped many cancer patients in the last 5 years by enhancing a patient's immune system to fight cancer. Anti-Programmed Death (PD-1) immunotherapy drugs such as pembrolizumab and nivolumab remove the breaks from cancer-fighting immune cells and have been effective in treating some melanoma patients. Despite the major breakthrough of immunotherapy in oncology treatment, many patients do not respond to this new class of anti-cancer drugs. Recently, evidence suggests that the microorganisms living in a patient's intestines play a major role in modifying the response to anti-PD-1drugs. Patients who respond to these drugs have a unique and healthy group of microorganisms in their gut. Therefore, positive modification of a cancer patient's gut microorganisms to create a more diverse and healthy microbiome may improve the response to immunotherapy. One method of modifying the microbiome is Fecal Microbial Transplantation (FMT) that is already being successfully used in the clinic to treat non-cancer patients with persistent bacterial infections.

In this study, the investigators will combine FMT with the approved immunotherapy drugs pembrolizumab or nivolumab that are the standard of care for the treatment of advanced melanoma. The purpose of this study is to examine the safety of combining these two therapies in melanoma patients. The investigator will use fecal material from a healthy donor selected via our stringent protocol that is Health Canada approved. In addition to assessing the safety of the combination, the investigator will also study the effect of FMT on the immune system and microbial ecosystem of the gut.

研究概览

地位

主动,不招人

条件

研究类型

介入性

注册 (估计的)

20

阶段

  • 阶段1

联系人和位置

本节提供了进行研究的人员的详细联系信息,以及有关进行该研究的地点的信息。

学习地点

    • Ontario
      • London、Ontario、加拿大、N6A 5W9
        • London Regional Cancer Program
      • Montréal、Ontario、加拿大、H2X 0C1
        • CHUM
    • Quebec
      • Montreal、Quebec、加拿大、H3T 1E2
        • Jewish General Hospital

参与标准

研究人员寻找符合特定描述的人,称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

19年 及以上 (成人、年长者)

接受健康志愿者

不

有资格学习的性别

全部

描述

Inclusion Criteria:

  • Patients must be 18-years old or older
  • Patients must have a confirmed diagnosis of unresectable or metastatic cutaneous melanoma (BRAF wild type or mutant)
  • Patients with ECOG performance of 0-2
  • Patients must be able to provide written informed consent and understand the infectious risks associated with FMT administration
  • Must understand non-infectious risks associated with FMT administration
  • Ability to ingest capsules
  • Understand that data regarding the long-term safety risk of FMT are lacking
  • Patients receiving systemic steroids at physiologic doses are permitted to enroll assuming steroid dose is not above the acceptable threshold (> 10 mg prednisone daily or equivalent)
  • Have measurable disease as per RECIST version 1.1

Exclusion Criteria:

  • Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.

  • Current or recent [in the last 90 days] exposure to high dose oral or IV corticosteroids

    o Patients who require intermittent use of bronchodilators or local steroid injections are not excluded from the study

  • Has a diagnosis of immunodeficiency (e.g. HIV, transplantation) or receiving systemic steroid therapy (>10mg prednisone daily or equivalent) or any other form of immunosuppressive therapy prior to trial treatment

  • Ongoing use of antibiotics or previous use of antibiotics in the last two weeks prior to the FMT procedure

  • Presence of a chronic intestinal disease (e.g. Celiac, malabsorption, colonic tumor)

  • Presence of absolute contra-indications to FMT administration

    • Toxic megacolon
    • Severe dietary allergies (e.g. shellfish, nuts, seafood)
    • Inflammatory bowel disease
    • Anatomic contra-indications to colonoscopy
  • Expected to require any other form of systemic or localized anti-neoplastic therapy while on study

  • Has a known history of a hematologic malignancy, primary brain tumor or sarcoma, or of another primary solid tumor, unless the patient has undergone potentially curative therapy with no evidence of that disease for five years

    o NOTE: This time requirement also does not apply to patients who underwent successful definitive resection of basal or squamous cell carcinoma of the skin, superficial bladder cancer, in situ cancers including cervical cancer, breast cancer, melanoma, or other in situ cancers.

  • Active central nervous system (CNS) metastases and/or leptomeningeal involvement

  • Patients with leptomeningeal disease (leptomeningeal enhancement on MRI/CT imaging and/or positive CSF cytology)

  • Has an active autoimmune disease or a documented history of autoimmune disease or syndrome that requires systemic steroids or immunosuppressive agents.

    o Patients with vitiligo, type I diabetes, resolved childhood asthma/atopy are exceptions to this rule

  • A history of (non-infectious) pneumonitis that required steroids or current pneumonitis

  • Has serious concomitant illnesses, such as: cardiovascular disease (uncontrolled congestive heart failure, hypertension, cardiac ischemia, myocardial infarction, and severe cardiac arrhythmia), bleeding disorders, autoimmune diseases, severe obstructive or restrictive pulmonary diseases, active systemic infections, and inflammatory bowel disorders

    o This includes HIV or AIDS-related illness, or active HBV and HCV

  • Has an active infection requiring systemic therapy.

  • Patient has received a live vaccine within 4 weeks prior to the first dose of treatment

    o Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.

  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial

学习计划

本节提供研究计划的详细信息,包括研究的设计方式和研究的衡量标准。

研究是如何设计的?

设计细节

  • 主要用途:治疗
  • 分配:不适用
  • 介入模型:单组作业
  • 屏蔽:无(打开标签)

武器和干预

参与者组/臂
干预/治疗
实验性的:Study Intervention

Fecal Microbial Transplantation - all patients registered on study will receive one dose (80-100mg) of FMT. This is a single arm, unblinded study.

All patients in this trial will receive FMT at least one week prior to treatment with approved immunotherapy (either pembrolizumab or nivolumab). Samples for FMT are sourced at and by the microbiology group under the supervision of Dr. Silverman at St Joseph's Hospital. Donor screening procedures are described in appendix 4. Transplant will be from one single donor for all participants unless Dr. Silverman's lab considers the need for more than one donor based on availability of donors. There will be no "mixture" of donor samples.

Donor samples are manufactured into capsules according to Kao et al, 2017.

研究衡量的是什么?

主要结果指标

结果测量
措施说明
大体时间
To evaluate the safety of combining Fecal Microbial Transplantation (FMT) using intestinal bacteria existing in the stool of healthy donors with immunotherapy in melanoma patients.
大体时间:60 months

Toxicity assessments and concurrent medication review will occur at every visit throughout immunotherapy treatment. Any adverse events after FMT administration will be followed until resolution or until judged stable by the investigator.

60 months

次要结果测量

结果测量
措施说明
大体时间
Assess Objective Response Rate
大体时间:At baseline and every 12 weeks thereafter up to 60 months

To evaluate whether combination of FMT and immunotherapy can enhance antitumor effect in melanoma patients by assessing the objective response rate (ORR; the rate of complete response plus partial response) as per the RECIST 1.1 criteria including immune-related response criteria.

At baseline and every 12 weeks thereafter up to 60 months
To Evaluate the effect(s) combination FMT and immunotherapy has on the gut microbiome
大体时间:At baseline, prior to 1st dose of immunotherapy (1 week post FMT) and 2nd dose of immunotherapy (2, 3, or 4 weeks post FMT depending on type of immunotherapy received), and at the 3 month follow-up visit

Stool sample for microbiome analysis will be collected in the form of used (visibly soiled) toilet paper packed in a labeled biohazard bad and brought with the participant to clinic. The stool sample can be obtained by the patient from a bowel movement up to 3 days prior to the visit.

At baseline, prior to 1st dose of immunotherapy (1 week post FMT) and 2nd dose of immunotherapy (2, 3, or 4 weeks post FMT depending on type of immunotherapy received), and at the 3 month follow-up visit
Evaluate the effect(s) combination FMT and immunotherapy has on changes in immune blood biomarkers
大体时间:At baseline, prior to 1st dose of immunotherapy (1 week post FMT) and 2nd dose of immunotherapy(2, 3, or 4 weeks post FMT depending on type of immunotherapy received), and at the 3 month follow-up visit

blood samples will be collected to assess changes in immune blood biomarkers before and after FMT administration by assessing Complete Blood Counts (WBC, HGB, platelets, neutrophils, lymphocytes, monocytes, eosinophils, basophils)

At baseline, prior to 1st dose of immunotherapy (1 week post FMT) and 2nd dose of immunotherapy(2, 3, or 4 weeks post FMT depending on type of immunotherapy received), and at the 3 month follow-up visit
Evaluate the effect(s) combination FMT and immunotherapy has on changes in immune blood biomarkers
大体时间:At baseline, prior to 1st dose of immunotherapy (1 week post FMT) and 2nd dose of immunotherapy(2, 3, or 4 weeks post FMT depending on type of immunotherapy received), and at the 3 month follow-up visit

blood samples will be collected to assess changes in immune blood biomarkers before and after FMT administration by assessing circulating T cells

At baseline, prior to 1st dose of immunotherapy (1 week post FMT) and 2nd dose of immunotherapy(2, 3, or 4 weeks post FMT depending on type of immunotherapy received), and at the 3 month follow-up visit
Evaluate the effect(s) combination FMT and immunotherapy has on changes in immune blood biomarkers
大体时间:At baseline, prior to 1st dose of immunotherapy (1 week post FMT) and 2nd dose of immunotherapy(2, 3, or 4 weeks post FMT depending on type of immunotherapy received), and at the 3 month follow-up visit

blood samples will be collected to assess changes in immune blood biomarkers before and after FMT administration by assessing checkpoint molecules including PD-1, PD-L1, TIM-3, LAG-3, TIGIT

At baseline, prior to 1st dose of immunotherapy (1 week post FMT) and 2nd dose of immunotherapy(2, 3, or 4 weeks post FMT depending on type of immunotherapy received), and at the 3 month follow-up visit
Evaluate the effect(s) combination FMT and immunotherapy has on changes in immune blood biomarkers
大体时间:At baseline, prior to 1st dose of immunotherapy (1 week post FMT) and 2nd dose of immunotherapy(2, 3, or 4 weeks post FMT depending on type of immunotherapy received), and at the 3 month follow-up visit

blood samples will be collected to assess changes in immune blood biomarkers before and after FMT administration by assessing immune markers such as HLA-DR CD38 and CD28

At baseline, prior to 1st dose of immunotherapy (1 week post FMT) and 2nd dose of immunotherapy(2, 3, or 4 weeks post FMT depending on type of immunotherapy received), and at the 3 month follow-up visit
Evaluate the effect(s) combination FMT and immunotherapy has on patient's metabolomics
大体时间:At baseline, prior to 1st dose of immunotherapy (1 week post FMT) and 2nd dose of immunotherapy (2, 3, or 4 weeks post FMT depending on type of immunotherapy received), and at the 3 month follow-up visit

A urine sample will be collected for metabolomics analysis.

At baseline, prior to 1st dose of immunotherapy (1 week post FMT) and 2nd dose of immunotherapy (2, 3, or 4 weeks post FMT depending on type of immunotherapy received), and at the 3 month follow-up visit

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

调查人员

  • 首席研究员:John Lenehan, MD、London Regional Cancer Program

出版物和有用的链接

负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查,以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (实际的)

2019年3月27日

初级完成 (实际的)

2021年9月14日

研究完成 (估计的)

2027年2月1日

研究注册日期

首次提交

2018年11月16日

首先提交符合 QC 标准的

2018年12月10日

首次发布 (实际的)

2018年12月11日

研究记录更新

最后更新发布 (实际的)

2026年11月4日

上次提交的符合 QC 标准的更新

2026年11月2日

最后验证

2026年10月1日

更多信息

与本研究相关的术语

药物和器械信息、研究文件

研究美国 FDA 监管的药品

不

研究美国 FDA 监管的设备产品

不

此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.

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