CHemotherapy and Stool Transplant in PDAC (CHASe-PDAC)

Официальное название

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.

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Fecal Microbiota Transplantation
  Fecal Microbiota Transplantation with 100 g of healthy donor stool in 36-40 oral capsules once Other Names: * FMT * Stool Transplant * Poop Transplant
• Препарат PEG3350
  Polyethylene Glycol 3350 17 g oral dissolved in 4 litres of water consumed the evening before FMT. Other Names: * PEG3350 * RestoraLAX * MiraLAX
• Препарат Gemcitabine
  Gemcitabine 1000 mg/m2/day IV on Days 1, 8, and 15 of each 28-day cycle. Other Names: \- Gemzar
• Препарат nab-Paclitaxel
  nab-Paclitaxel 125 mg/m2/day IV on Days 1, 8, and 15 of each 28-day cycle. Other Names: \- Abraxane

Первичные конечные точки

• Adverse Events [Срок оценки: Approximately end of year 4 (Study Completion)]

Вторичные конечные точки (5)

• Progression-Free Survival [Срок оценки: Time between study enrollment and the time of disease progression, death, or date of last follow-up, whichever occurs first.]
• Overall Survival [Срок оценки: Until the date of death from any cause assessed from the date of FMT up to 24 months.]
• Tolerability of consuming the FMT capsules [Срок оценки: 24 months]
• Objective Response Rate [Срок оценки: Approximately 4 years (end of study)]
• Clinical Benefit Rate [Срок оценки: Approximately 4 years (end of study)]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Канада · 1 центр

• Verspeeten Family Cancer Centre (formerly known as the London Regional Cancer Program) Lon — London

Идентификаторы

NCT: NCT06393400 · ReDA 14577

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗