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Gemcitabine

Paclitaxel

Albumin-Bound Paclitaxel

Laxatives

Polyethylene glycol 3350

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Antimetabolites

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.

Fecal Microbiota Transplantation with 100 g of healthy donor stool in 36-40 oral capsules once

Other Names:

* FMT
* Stool Transplant
* Poop Transplant

Fecal Microbiota Transplantation

Polyethylene Glycol 3350 17 g oral dissolved in 4 litres of water consumed the evening before FMT.

Other Names:

* PEG3350
* RestoraLAX
* MiraLAX

PEG3350

Gemcitabine 1000 mg/m2/day IV on Days 1, 8, and 15 of each 28-day cycle.

Other Names:

- Gemzar

nab-Paclitaxel 125 mg/m2/day IV on Days 1, 8, and 15 of each 28-day cycle.

Other Names:

- Abraxane

nab-Paclitaxel

John G Lenehan, MD

John G Lenehan, MD, FRCPC

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.

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.

CHemotherapy And Stool Transplant in PDAC (CHASe-PDAC)

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.

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.

Determined using RECIST 1.1 criteria to evaluate changes in tumour size on routine imaging and quantified using the Kaplan-Meier method.

Quantified using the Kaplan-Meier method alone.

The tolerability of consuming approximately 40 capsules in patients with PDAC will be assessed by study personnel through direct observation of the FMT process. Patients with advanced PDAC are often unwell, cachectic, anorexic, and experiencing nausea associated with the cancer process. Adequate intake of calories and hydration are routinely a challenge in this patient population. Before a larger study can be contemplated, the feasibility and tolerability of consuming the large number of capsules needs to be demonstrated in a smaller study like this.

A reduction in size of PDAC tumours is often not achieved or dramatic when they occur, therefore the ORR is not considered a benchmark of success in this study. However, some patients may benefit from a reduction in tumour volume with respect to cancer-related symptoms such as gastric outlet obstruction resulting from extrinsic compression by the tumour. The ORR will be assessed given its potential to be clinically meaningful and will be determined using the RECIST 1.1 criteria.

The CBR may be more clinically relevant to patients with PDAC where SD directly relates to the duration of PFS and few achieve a CR or PR.

Spots Global Cancer Trial Database for pdac, fecal microbial transplantation, gut microbiome