An Open-label, Single-arm, Phase 1 Study of the Combination of FMT and Gemcitabine with Nab-paclitaxel As First-line Therapy in Patients with Advanced Pancreatic Ductal Adenocarcinoma.
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- John Lenehan
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Adverse Events
研究概览
简要总结
To confirm the safety of combining oral fecal microbiota transplantation (FMT) with gemcitabine and nab-paclitaxel chemotherapy as first line treatment in patients with unresectable or metastatic pancreatic ductal adenocarcinoma.
详细描述
This is a phase 1 open-labelled, non-randomized safety trial examining oral fecal microbiota transplantation (FMT) with healthy donor stool in combination with standard of care (SOC) gemcitabine and nab-paclitaxel (GnP) in patients with advanced (unresectable and metastatic) pancreatic ductal adenocarcinoma (PDAC) as first-line therapy. A total of 20 eligible patients will be treated with study treatment. The purpose of the trial is to confirm the safety of combined therapy, assess clinical outcomes, perform gut microbiome analysis, systemic immune profiling, and explore patient-related outcomes. This trial will be conducted at the Verspeeten Family Cancer Centre (formerly known as the London Regional Cancer Program) at London Health Sciences Centre.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must be 18-years old or older
- •Patients must have a confirmed diagnosis of unresectable or metastatic pancreatic ductal adenocarcinoma. Diagnosis confirmation may include pathologic assessment or radiographic/biomarker determination of PDAC when obtaining a tumour sample is not feasible/successful. The latter case requires review at the Pancreas Multi-disciplinary Case Conference (MCC)
- •Patients with ECOG performance of 0-2
- •Patients who have consented to treatment with first-line gemcitabine with nab-paclitaxel at the discretion of their primary oncologist. Patients must receive at least one dose of both chemotherapy agents to be considered eligible for evaluation.
- •Patients must be able to provide written informed consent and understand the infectious risks associated with FMT administration
- •Patients must understand that there are non-infectious risks associated with FMT administration
- •Ability to ingest capsules
- •Understand that data regarding the long-term safety risk of FMT are lacking
- •Have evaluable disease as per RECIST version 1.1
- •Patients may receive other localized therapies with palliative intent while on therapy to include external beam radiation to areas of metastatic disease. Stratification of outcomes will include identifying patients that receive palliative radiation to the primary tumour itself.
排除标准
- •Previously received cytotoxic chemotherapy with curative or non-curative intent for PDAC
- •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
- •Has a diagnosis of immunodeficiency (e.g. HIV, organ transplantation)
- •Ongoing use of antibiotics or previous use of antibiotics within 7 days prior to the FMT procedure
- •Probiotic supplements and food products labeled as containing probiotics must be discontinued a minimum of 72 hours before FMT administration and are not permitted during the first 3 months of chemotherapy treatment
- •Presence of a chronic intestinal disease (e.g. Celiac, malabsorption, primary colonic tumor)
- •Presence of absolute contra-indications to FMT administration
- •Toxic megacolon
- •Severe dietary allergies (e.g. shellfish, nuts, seafood)
- •Inflammatory bowel disease
- •Has serious concomitant illnesses, such as: cardiovascular disease (uncontrolled congestive heart failure, uncontrolled 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
- •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
- •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
- •Special considerations include patients who are unable to tolerate the combination of gemcitabine with nab-paclitaxel, and subsequently after starting chemotherapy are transitioned to gemcitabine alone at the discretion of their treating oncologist. Such patients will not be removed or disqualified from continuing in the study but their clinical outcomes will be stratified between those who received nab-paclitaxel with gemcitabine and those who transitioned to gemcitabine alone. In general, this scenario is not expected to commonly occur in this trial.
研究组 & 干预措施
Fecal Microbiota Transplantation
A single Fecal Microbiota Transplantation (FMT) with 100 g of healthy stool in 36-40 oral capsules once 24 hours after Polyethylene Glycol laxative preparation, followed by gemcitabine 1000 mg/m2 intravenously (IV) and nab-paclitaxel 125 mg/m2 IV on Day 1, Day 8, and Day 15 of each 28-day cycle at least 7 days after FMT.
干预措施: Fecal Microbiota Transplantation (Drug)
Fecal Microbiota Transplantation
A single Fecal Microbiota Transplantation (FMT) with 100 g of healthy stool in 36-40 oral capsules once 24 hours after Polyethylene Glycol laxative preparation, followed by gemcitabine 1000 mg/m2 intravenously (IV) and nab-paclitaxel 125 mg/m2 IV on Day 1, Day 8, and Day 15 of each 28-day cycle at least 7 days after FMT.
干预措施: PEG3350 (Drug)
Fecal Microbiota Transplantation
A single Fecal Microbiota Transplantation (FMT) with 100 g of healthy stool in 36-40 oral capsules once 24 hours after Polyethylene Glycol laxative preparation, followed by gemcitabine 1000 mg/m2 intravenously (IV) and nab-paclitaxel 125 mg/m2 IV on Day 1, Day 8, and Day 15 of each 28-day cycle at least 7 days after FMT.
干预措施: Gemcitabine (Drug)
Fecal Microbiota Transplantation
A single Fecal Microbiota Transplantation (FMT) with 100 g of healthy stool in 36-40 oral capsules once 24 hours after Polyethylene Glycol laxative preparation, followed by gemcitabine 1000 mg/m2 intravenously (IV) and nab-paclitaxel 125 mg/m2 IV on Day 1, Day 8, and Day 15 of each 28-day cycle at least 7 days after FMT.
干预措施: nab-Paclitaxel (Drug)
结局指标
主要结局
Adverse Events
时间窗: Approximately end of year 4 (Study Completion)
FMT in combination with systemic therapy in patients with advanced PDAC has not been studied to our knowledge. Prior to proceeding with a larger study, this phase I study will include 20 patients receiving G-nP who will receive a single FMT with healthy donor stool prior to the first dose of chemotherapy. There are well-known toxicities associated with these 2 chemotherapeutic agents, several of which affect the gastrointestinal tract. The most common side effects resulting from FMT are primarily mild gastrointestinal effects. FMT has been found to be safe when combined with ICIs and there has been no increase in the number of toxicities or severity observed. The measure of safety in this trial will be assessing for treatment-related adverse events that will be graded according to the NCI-CTCAE v5. A positive trial result with respect to toxicity will be designated if there are no unexpected or more severe toxicities associated than with the chemotherapy drugs alone.
次要结局
- Progression-Free Survival(Time between study enrollment and the time of disease progression, death, or date of last follow-up, whichever occurs first.)
- Tolerability of consuming the FMT capsules(24 months)
- Objective Response Rate(Approximately 4 years (end of study))
- Clinical Benefit Rate(Approximately 4 years (end of study))
- Overall Survival(Until the date of death from any cause assessed from the date of FMT up to 24 months.)
研究者
John Lenehan
Principal Investigator
London Health Sciences Centre Research Institute and Lawson Research Institute of St. Joseph's