Chemotherapy + Stool Transplant for Pancreatic Cancer

(CHASe-PDAC Trial)

Overseen By John G Lenehan, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: John Lenehan

Must be taking: Gemcitabine, Nab-paclitaxel

Must not be taking: Antibiotics, Probiotics

Disqualifiers: Immunodeficiency, Chronic intestinal disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

Duration: 28-day cycles

20 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must stop using antibiotics 7 days before the stool transplant and avoid probiotics 72 hours before and during the first 3 months of chemotherapy.

What data supports the effectiveness of the treatment Fecal Microbiota Transplantation combined with chemotherapy for pancreatic cancer?

Research shows that the combination of nab-paclitaxel and gemcitabine is effective as a first-line chemotherapy for patients with metastatic pancreatic cancer, improving survival compared to gemcitabine alone. ^{1 2 3 4 5}

Is the combination of chemotherapy drugs nab-paclitaxel and gemcitabine safe for humans?

The combination of nab-paclitaxel and gemcitabine has shown an acceptable safety profile in patients with advanced solid tumors, including pancreatic cancer, according to research studies. ^{6 7 8 9 10}

How is the chemotherapy and stool transplant treatment for pancreatic cancer different from other treatments?

This treatment is unique because it combines chemotherapy drugs, gemcitabine and nab-paclitaxel, with a stool transplant, which is not a standard approach for pancreatic cancer. The stool transplant aims to improve gut health and potentially enhance the effectiveness of chemotherapy, offering a novel way to tackle the disease. ^{2 3 11 12 13}

What is the purpose of this trial?

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.

Eligibility Criteria

This trial is for individuals with unresectable or metastatic pancreatic ductal adenocarcinoma who haven't had treatment before. Participants must be able to take oral medication and have acceptable blood test results. People with certain digestive conditions, immune system disorders, or those using antibiotics recently may not qualify.

Inclusion Criteria

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

Understand that data regarding the long-term safety risk of FMT are lacking

Exclusion Criteria

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

I am currently taking antibiotics or have taken them within the last week.

I haven't taken any probiotics for 3 days before starting treatment and won't during the first 3 months of chemotherapy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single Fecal Microbiota Transplantation (FMT) followed by gemcitabine and nab-paclitaxel chemotherapy on Day 1, Day 8, and Day 15 of each 28-day cycle

28-day cycles

3 visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of adverse events and clinical outcomes

Approximately 4 years

Long-term follow-up

Participants are monitored for overall survival and progression-free survival

Up to 24 months

Treatment Details

Interventions

• Fecal Microbiota Transplantation
• Gemcitabine
• nab-Paclitaxel

Trial Overview The study tests if taking a fecal microbiota transplant (FMT) by mouth along with chemotherapy drugs gemcitabine and nab-paclitaxel is safe for patients as a first-line treatment for advanced pancreatic cancer.

Participant Groups

Group I: Fecal Microbiota Transplantation Experimental Treatment 4 Interventions

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.

Gemcitabine is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in United States as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in Canada as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in Japan as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Who Is Running the Clinical Trial?

John Lenehan

Lead Sponsor

Trials

1

Recruited

20+

Findings from Research

A study of 5465 patients with advanced pancreatic cancer in Ontario showed that the introduction of new chemotherapy regimens, GEMNAB and FOLFIRINOX, significantly improved overall survival rates over time, with median survival increasing from 5.6 months to 7.6 months between 2008 and 2018.

FOLFIRINOX was found to provide better overall survival compared to GEMNAB, particularly in younger and healthier patients, while GEMNAB still showed improved survival compared to the older standard treatment, gemcitabine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Association of Drug-Funding Reimbursement With Survival Outcomes and Use of New Systemic Therapies Among Patients With Advanced Pancreatic Cancer. Raphael, MJ., Raskin, W., Habbous, S., et al.[2023]

The combination of nab-paclitaxel and gemcitabine is a safe and effective first-line chemotherapy for patients with metastatic pancreatic cancer, as demonstrated in a clinical practice setting with four patients.

Despite some patients having elevated bilirubin levels and significant comorbidities, the treatment was well tolerated, leading to clinical remission or disease stabilization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line nab-paclitaxel and gemcitabine in patients with metastatic pancreatic cancer from routine clinical practice. Vogel, A., Pelzer, U., Salah-Eddin, AB., et al.[2022]

In a Phase II trial involving 34 patients with advanced pancreatic carcinoma, the combination of gemcitabine and docetaxel was found to be well tolerated, with only 12% of patients experiencing severe complications like febrile neutropenia.

The treatment showed moderate efficacy, with an objective response rate of 18% and a median survival of 8.9 months, suggesting that while the combination therapy is manageable, further randomized studies are needed to determine its effectiveness compared to single-agent treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase II study of gemcitabine and docetaxel in patients with metastatic pancreatic carcinoma. Ryan, DP., Kulke, MH., Fuchs, CS., et al.[2022]

In a randomized phase II trial involving 106 patients with advanced pancreatic cancer, the combination of gemcitabine and S-1 significantly improved progression-free survival (PFS) to 5.4 months compared to 3.6 months with gemcitabine alone.

The combination therapy also showed a longer overall survival (OS) of 13.5 months versus 8.8 months for gemcitabine alone, although this difference was not statistically significant, indicating potential benefits without increased severe adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multicentre randomised phase II trial of gemcitabine alone vs gemcitabine and S-1 combination therapy in advanced pancreatic cancer: GEMSAP study. Nakai, Y., Isayama, H., Sasaki, T., et al.[2022]

In a study of 53 patients with inoperable or metastatic pancreatic cancer, the combination of gemcitabine (GEM) and capecitabine (CAP) resulted in an 18.9% rate of objective partial responses and a median overall survival of 8 months, indicating its potential efficacy as a treatment option.

The treatment was generally well tolerated, with 53% of patients experiencing pain improvement and 36% showing weight gain, while serious side effects like grade 3 anemia and neutropenia were relatively low, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Front-line treatment of inoperable or metastatic pancreatic cancer with gemcitabine and capecitabine: an intergroup, multicenter, phase II study. Stathopoulos, GP., Syrigos, K., Polyzos, A., et al.[2022]

In a study of 28 patients with gemcitabine-refractory pancreatic cancer, the combination of 5-fluorouracil and paclitaxel showed some efficacy, with 10% of patients achieving a partial response and 20% having stable disease.

The median overall survival was 7.6 months, indicating that this treatment may provide a viable option for patients who have not responded to previous gemcitabine-based therapies, despite some associated toxicities like neutropenia and neuropathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of 5-fluorouracil and paclitaxel in patients with gemcitabine-refractory pancreatic cancer. Kim, YJ., Bang, S., Park, JY., et al.[2022]

In a study of 23 patients with metastatic pancreas adenocarcinoma, the combination of nab-paclitaxel and gemcitabine resulted in a disease control rate of 43.4%, indicating a significant clinical benefit for patients with advanced disease.

The treatment was generally well-tolerated, with manageable adverse effects, and led to improvements in performance status and pain for many patients, highlighting its potential as a feasible option for those with poor health status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nab-Paclitaxel and Gemcitabine in Advanced Pancreatic Cancer: The One-year Experience of the National Cancer Institute of Naples. Ottaiano, A., Capozzi, M., DE Divitiis, C., et al.[2022]

In a study of 27 patients with unresectable pancreatic cancer, nab paclitaxel plus gemcitabine was found to be effective and well-tolerated in elderly patients aged 75 and older, showing similar disease control rates and overall survival compared to younger patients.

Despite a lower relative dose intensity of the drugs in the elderly group, the safety profile was comparable, with neutropenia being the most common severe adverse event, indicating that this treatment regimen can be safely administered to older patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of nab paclitaxel plus gemcitabine in elderly patients over 75 years with unresectable pancreatic cancer compared with younger patients. Ishimoto, U., Kinoshita, A., Hirose, Y., et al.[2022]

In a review of seven randomized controlled trials involving 1544 patients, adding a targeted agent to the gemcitabine plus nab-paclitaxel (GA) regimen did not significantly improve overall survival (OS) or progression-free survival (PFS) compared to GA alone.

While the addition of a targeted agent did not enhance efficacy, it was associated with a higher incidence of grade 3/4 diarrhea, indicating that the combination may increase toxicity without providing additional benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Meta-analysis of gemcitabine plus nab-paclitaxel combined with targeted agents in the treatment of metastatic pancreatic cancer. Li, ZH., Ma, YJ., Jia, ZH., et al.[2022]

Itacitinib, a selective JAK1 inhibitor, combined with nab-paclitaxel and gemcitabine, showed an acceptable safety profile and clinical activity in patients with advanced solid tumors, including pancreatic cancer, with a 24% overall response rate across various doses.

The study indicated that while itacitinib was tolerated at lower doses, treatment-related toxicities such as neutropenia and fatigue were common, leading to dose adjustments; however, the study was terminated early due to negative results from a related phase III trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase Ib/II Study of the JAK1 Inhibitor, Itacitinib, plus nab-Paclitaxel and Gemcitabine in Advanced Solid Tumors. Beatty, GL., Shahda, S., Beck, T., et al.[2022]

In the phase 3 MPACT trial, nab-paclitaxel plus gemcitabine showed significantly greater reductions in both primary pancreatic tumors and metastatic lesions compared to gemcitabine alone, indicating its efficacy in treating metastatic pancreatic cancer.

The study found that baseline pancreatic tumor burden was a strong predictor of overall survival, and both treatment regimens resulted in consistent tumor shrinkage over time, highlighting the potential of nab-paclitaxel plus gemcitabine for improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor Reduction in Primary and Metastatic Pancreatic Cancer Lesions With nab-Paclitaxel and Gemcitabine: An Exploratory Analysis From a Phase 3 Study. Kunzmann, V., Ramanathan, RK., Goldstein, D., et al.[2022]

In a study of 485 patients with localized pancreatic cancer, those treated with FOLFIRINOX showed higher rates of partial response according to RECIST criteria compared to those treated with gemcitabine plus nab-paclitaxel (GA), indicating better initial tumor response.

Despite the higher response rates and more frequent surgeries (pancreatectomy) in the FOLFIRINOX group, overall survival rates were similar between the two treatment regimens, suggesting that while FOLFIRINOX may be more effective in shrinking tumors, it does not necessarily lead to longer survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Response and Survival Associated With First-line FOLFIRINOX vs Gemcitabine and nab-Paclitaxel Chemotherapy for Localized Pancreatic Ductal Adenocarcinoma. Perri, G., Prakash, L., Qiao, W., et al.[2022]

Chemotherapy regimens using gemcitabine or 5-FU have been shown to provide benefits for patients with advanced pancreatic carcinoma.

Adjuvant chemotherapy after complete surgical removal of the tumor may improve survival rates, as indicated by some studies, highlighting the potential for enhanced treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Chemotherapy of pancreatic carcinoma]. Lutz, MP.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

The Association of Drug-Funding Reimbursement With Survival Outcomes and Use of New Systemic Therapies Among Patients With Advanced Pancreatic Cancer. [2023]

2. Greece pubmed.ncbi.nlm.nih.gov

First-line nab-paclitaxel and gemcitabine in patients with metastatic pancreatic cancer from routine clinical practice. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

A Phase II study of gemcitabine and docetaxel in patients with metastatic pancreatic carcinoma. [2022]

4. England pubmed.ncbi.nlm.nih.gov

A multicentre randomised phase II trial of gemcitabine alone vs gemcitabine and S-1 combination therapy in advanced pancreatic cancer: GEMSAP study. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Front-line treatment of inoperable or metastatic pancreatic cancer with gemcitabine and capecitabine: an intergroup, multicenter, phase II study. [2022]

6. Germany pubmed.ncbi.nlm.nih.gov

Phase II study of 5-fluorouracil and paclitaxel in patients with gemcitabine-refractory pancreatic cancer. [2022]

7. Greece pubmed.ncbi.nlm.nih.gov

Nab-Paclitaxel and Gemcitabine in Advanced Pancreatic Cancer: The One-year Experience of the National Cancer Institute of Naples. [2022]

8. Germany pubmed.ncbi.nlm.nih.gov

The efficacy and safety of nab paclitaxel plus gemcitabine in elderly patients over 75 years with unresectable pancreatic cancer compared with younger patients. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Meta-analysis of gemcitabine plus nab-paclitaxel combined with targeted agents in the treatment of metastatic pancreatic cancer. [2022]

10. England pubmed.ncbi.nlm.nih.gov

A Phase Ib/II Study of the JAK1 Inhibitor, Itacitinib, plus nab-Paclitaxel and Gemcitabine in Advanced Solid Tumors. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

Tumor Reduction in Primary and Metastatic Pancreatic Cancer Lesions With nab-Paclitaxel and Gemcitabine: An Exploratory Analysis From a Phase 3 Study. [2022]

12. United States pubmed.ncbi.nlm.nih.gov

Response and Survival Associated With First-line FOLFIRINOX vs Gemcitabine and nab-Paclitaxel Chemotherapy for Localized Pancreatic Ductal Adenocarcinoma. [2022]

13. Switzerland pubmed.ncbi.nlm.nih.gov

[Chemotherapy of pancreatic carcinoma]. [2022]