CHemotherapy and Stool Transplant in PDAC (CHASe-PDAC)

NCT06393400 | Recruiting Phase 1 DMC

• 1 other identifier: ReDA 14577
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Unresectable or Metastatic Advanced Pancreatic Ductal Adenocarcinoma

Keywords

PDAC, Fecal Microbial Transplantation, Gut Microbiome

Outcome Measures

Primary Outcomes (1)

• Adverse Events

  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.

  Approximately end of year 4 (Study Completion)

Secondary Outcomes (5)

• Progression-Free Survival

  Time between study enrollment and the time of disease progression, death, or date of last follow-up, whichever occurs first.

• Overall Survival

  Until the date of death from any cause assessed from the date of FMT up to 24 months.

• 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)

Study Arms (1)

Fecal Microbiota Transplantation

EXPERIMENTAL

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.

Drug: Fecal Microbiota Transplantation; Drug: PEG3350; Drug: Gemcitabine; Drug: nab-Paclitaxel

Interventions

Fecal Microbiota Transplantation DRUG

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

PEG3350 DRUG

Polyethylene Glycol 3350 17 g oral dissolved in 4 litres of water consumed the evening before FMT. Other Names: * PEG3350 * RestoraLAX * MiraLAX

Fecal Microbiota Transplantation

Gemcitabine DRUG

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

Fecal Microbiota Transplantation

nab-Paclitaxel DRUG

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

Fecal Microbiota Transplantation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• John Lenehan: lead

Study Sites (1)

Verspeeten Family Cancer Centre (formerly known as the London Regional Cancer Program) London Health Sciences Centre

London, Ontario, N6A 5W9, Canada

RECRUITING

MeSH Terms

Conditions

Anophthalmia with pulmonary hypoplasia

Interventions

Fecal Microbiota Transplantation; polyethylene glycol 3350; Gemcitabine; 130-nm albumin-bound paclitaxel

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Central Study Contacts

John G Lenehan, MD

CONTACT

519-685-8640; John.Lenehan@lhsc.on.ca

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 18, 2024
• First Posted: May 1, 2024
• Study Start: January 8, 2025
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): February 1, 2028
• Last Updated: January 23, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)