Chemotherapy for Pancreatic Cancer

(PASS-01 Trial)

Recruiting at 5 trial locations

Overseen By Anna J Dodd

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University Health Network, Toronto

Must not be taking: Anticoagulants

Disqualifiers: Brain metastases, Uncontrolled illness, HRD genes, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 2-4 years

150 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a randomized multicentre phase II trial with a large translational component. The trial will evaluate the two standard chemotherapy regimens: modified folfirinox (mFFX) and gemcitabine/nab-paclitaxel (GA), in patients with untreated metastatic pancreatic ductal adenocarcinoma. Integrated into this phase II trial are a number of laboratory components including molecular profiling, patient derived organoid establishment, and drug testing sensitivity and other biomarkers.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, you must be suitable for treatment with the trial's chemotherapy regimens without contraindications, so it's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug Folfirinox, FOLFOXIRI, FOIL, Gemcitabine/nab-paclitaxel for pancreatic cancer?

Research shows that the drug combinations FOLFIRINOX and gemcitabine plus nab-paclitaxel improve survival in patients with advanced pancreatic cancer compared to using gemcitabine alone. These combinations have been shown to delay tumor progression and improve treatment outcomes in both clinical trials and real-world settings. ^{1 2 3 4 5}

What safety data exists for chemotherapy treatments like FOLFIRINOX and Gemcitabine/nab-paclitaxel for pancreatic cancer?

Both FOLFIRINOX and Gemcitabine/nab-paclitaxel are used for treating advanced pancreatic cancer and have different safety profiles. FOLFIRINOX may cause more vomiting and diarrhea, while Gemcitabine/nab-paclitaxel might lead to more anemia. Overall, both treatments are considered to have a reasonable safety profile for use in humans. ^{6 7 8 9 10}

How is the chemotherapy treatment for pancreatic cancer using FOLFIRINOX and gemcitabine/nab-paclitaxel different from other treatments?

The chemotherapy treatment using FOLFIRINOX and gemcitabine/nab-paclitaxel for pancreatic cancer is unique because it combines two powerful drug regimens that can be used sequentially to potentially overcome resistance and delay tumor progression. This approach offers a promising option for patients with advanced pancreatic cancer, especially when initial treatments fail. ^{1 2 8 11 12}

Research Team

Elizabeth Jaffee, MD

Principal Investigator

Johns Hopkins University

Jennifer J Knox, MD

Principal Investigator

University Health Network, Toronto

Eligibility Criteria

Adults with untreated metastatic pancreatic ductal adenocarcinoma can join this trial if they're fit for chemotherapy, have a life expectancy over 90 days, and can undergo a tumor biopsy. They must not have other serious health issues or prior PDAC treatments. Women of childbearing age need a negative pregnancy test and must use birth control.

Inclusion Criteria

Patients must be suitable for treatment with either mFFX and GA without contraindications to either regimen

Eastern Cooperative Group (ECOG) performance status 0-1 (Karnofsky ≥70%)

Life expectancy of greater than 90 days, as judged by the investigator

Exclusion Criteria

Patients with histology other than pancreatic ductal adenocarcinoma. Those with adenosquamous are allowed. Acinar tumors and colloid are excluded

Patients with one or more contraindications to tumor biopsy according to local institution's standard biopsy procedures

Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either modified FOLFIRINOX or Gemcitabine/nab-Paclitaxel as standard chemotherapy regimens

2-4 years

Follow-up

Participants are monitored for progression free survival and overall response rate using RECIST 1.1

2-4 years

Treatment Details

Interventions

• Folfirinox
• Gemcitabine/nab-paclitaxel

Trial Overview The study compares two standard chemo treatments for advanced pancreatic cancer: modified Folfirinox (mFFX) and Gemcitabine/nab-paclitaxel (GA). It includes molecular profiling to tailor treatment to the patient's specific cancer signature.

Participant Groups

Group I: Modified Folfirinox Active Control 1 Intervention

Modified FOLFIRINOX (Folinic acid/Leucovorin, 5-Fluouracil, Irinotecan, Oxaliplatin) administered intravenously. Given that both regimens are standard of care, study treatment will be administered as per standard of care at each institution including a maintenance therapy approach which is encouraged in both arms. Dose modifications, anti-emetics, supportive medications, and use of growth factors should follow institutional guidelines.

Group II: Gemcitabine/nab-Paclitaxel Active Control 1 Intervention

Gemcitabine/nab-Paclitaxel administered intravenously. Given that both regimens are standard of care, study treatment will be administered as per standard of care at each institution including a maintenance therapy approach which is encouraged in both arms. Dose modifications, anti-emetics, supportive medications, and use of growth factors should follow institutional guidelines.

Folfirinox is already approved in United States, European Union for the following indications:

Approved in United States as FOLFIRINOX for:

• Pancreatic cancer

Approved in European Union as FOLFIRINOX for:

• Pancreatic cancer

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Stand Up To Cancer

Collaborator

Trials

53

Recruited

40,100+

Cold Spring Harbor Laboratory

Collaborator

Trials

11

Recruited

20,100+

Memorial Sloan Kettering Cancer Center

Collaborator

Trials

1,998

Recruited

602,000+

Ontario Institute for Cancer Research

Collaborator

Trials

24

Recruited

9,200+

Johns Hopkins University

Collaborator

Trials

2,366

Recruited

15,160,000+

Dana-Farber Cancer Institute

Collaborator

Trials

1,128

Recruited

382,000+

Findings from Research

The sequential treatment of nab-paclitaxel/gemcitabine followed by FOLFIRINOX in metastatic pancreatic cancer showed a high objective response rate of 64.9% and acceptable toxicity, with no deaths reported during the study.

Patients experienced manageable side effects, primarily neutropenia and venous thromboembolism, while achieving a median progression-free survival of 10.5 months and overall survival of 15.1 months, indicating the treatment's potential effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sequential first-line treatment with nab-paclitaxel/gemcitabine and FOLFIRINOX in metastatic pancreatic adenocarcinoma: GABRINOX phase Ib-II controlled clinical trial. Assenat, E., de la Fouchardière, C., Portales, F., et al.[2022]

The introduction of FOLFIRINOX and gemcitabine plus nab-paclitaxel therapy significantly improved treatment outcomes for metastatic pancreatic cancer, with response rates increasing from 7.8% to 28.4% after these therapies were introduced.

Patients treated with the newer therapies experienced longer median progression-free survival (3.1 months to 5.4 months) and median overall survival (6.7 months to 10.2 months), indicating a substantial benefit in daily clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improvement of Treatment Outcomes for Metastatic Pancreatic Cancer: A Real-world Data Analysis. Sasaki, T., Kanata, R., Yamada, I., et al.[2022]

In a study of 486 patients with metastatic pancreatic cancer, those receiving nab-paclitaxel plus gemcitabine (nab-p + G) had a median age of 68 and worse performance status compared to those receiving FOLFIRINOX (FFX), who had a median age of 61 and better performance status.

Despite the differences in patient characteristics, the study found no significant differences in time to treatment failure (3.7 months for nab-p + G vs. 4.3 months for FFX) or overall survival (9.8 months for nab-p + G vs. 11.4 months for FFX), suggesting similar efficacy between the two chemotherapy regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Outcomes with First-Line Chemotherapy in a Large Retrospective Study of Patients with Metastatic Pancreatic Cancer Treated in a US Community Oncology Setting. Cartwright, TH., Parisi, M., Espirito, JL., et al.[2022]

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]

In a meta-analysis of 16 studies involving 3813 patients with metastatic pancreatic cancer, both GEM-NAB and FOLFIRINOX showed similar overall survival rates, despite FOLFIRINOX having a numerically longer median overall survival.

GEM-NAB was associated with lower rates of nausea and severe neutropenia compared to FOLFIRINOX, while FOLFIRINOX had lower rates of neurotoxicity and anemia, indicating that the choice between these treatments may depend on the patient's tolerance to side effects rather than a clear efficacy advantage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Effectiveness of Gemcitabine plus Nab-Paclitaxel and FOLFIRINOX in the First-Line Setting of Metastatic Pancreatic Cancer: A Systematic Review and Meta-Analysis. Pusceddu, S., Ghidini, M., Torchio, M., et al.[2020]

In a comparison of two chemotherapy regimens for metastatic pancreatic cancer, FOLFIRINOX (FFX) and gemcitabine + nab-paclitaxel (GN), both treatments showed equivalent overall survival of 11.1 months and similar progression-free survival rates, indicating comparable efficacy.

However, the safety profiles differed: GN was associated with more frequent grade 3/4 anemia, while FFX led to higher rates of grade 3/4 vomiting and diarrhea, suggesting that while both treatments are effective, their side effects vary significantly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Equivalent Efficacy but Different Safety Profiles of Gemcitabine Plus Nab-Paclitaxel and FOLFIRINOX in Metastatic Pancreatic Cancer. Rapposelli, IG., Casadei-Gardini, A., Vivaldi, C., et al.[2022]

In a single-center experience involving two cases of locally advanced pancreatic cancer, patients initially treated with neoadjuvant FOLFIRINOX chemotherapy, which had high response rates but potential hematologic toxicity, showed disease progression.

Subsequent treatment with nab-paclitaxel and gemcitabine resulted in significant response rates and a reasonable safety profile, suggesting this combination may be a viable second-line option for patients with unresectable pancreatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Resection of Locally Advanced Pancreatic Neoplasms after Neoadjuvant Chemotherapy with Nab-Paclitaxel and Gemcitabine following FOLFIRINOX Failure. Hahn, S., Ayav, A., Lopez, A.[2020]

In a study of 654 patients with metastatic pancreatic adenocarcinoma, the overall survival rates were similar for those treated with nab-Paclitaxel plus gemcitabine (nab-P + G) and FOLFIRINOX, with median overall survival of 12.1 months and 13.8 months, respectively.

Patients receiving nab-P + G experienced significantly lower rates of common side effects such as diarrhea, fatigue, and nausea compared to those treated with FOLFIRINOX, indicating a better tolerability profile for nab-P + G.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Effectiveness of nab-Paclitaxel Plus Gemcitabine vs FOLFIRINOX in Metastatic Pancreatic Cancer: A Retrospective Nationwide Chart Review in the United States. Kim, S., Signorovitch, JE., Yang, H., et al.[2022]

In a study of 670 Veterans with advanced pancreatic cancer, the combination of gemcitabine and nab-paclitaxel (Gem/NabP) showed similar overall survival rates compared to FOLFIRINOX, indicating that Gem/NabP is noninferior to FOLFIRINOX for this patient population.

The study utilized a novel tumor growth formula based on CA19-9 biomarker data, suggesting that this approach could be valuable for monitoring treatment responses and predicting outcomes in pancreatic cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine plus nab-paclitaxel versus FOLFIRINOX for unresected pancreatic cancer: Comparative effectiveness and evaluation of tumor growth in Veterans. Sigel, K., Zhou, M., Park, YA., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Sequential first-line treatment with nab-paclitaxel/gemcitabine and FOLFIRINOX in metastatic pancreatic adenocarcinoma: GABRINOX phase Ib-II controlled clinical trial. [2022]

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

Improvement of Treatment Outcomes for Metastatic Pancreatic Cancer: A Real-world Data Analysis. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Clinical Outcomes with First-Line Chemotherapy in a Large Retrospective Study of Patients with Metastatic Pancreatic Cancer Treated in a US Community Oncology Setting. [2022]

4. 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]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Intensified Neoadjuvant Chemotherapy with Nab-Paclitaxel plus Gemcitabine Followed by FOLFIRINOX in a Patient with Locally Advanced Unresectable Pancreatic Cancer. [2020]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Comparative Effectiveness of Gemcitabine plus Nab-Paclitaxel and FOLFIRINOX in the First-Line Setting of Metastatic Pancreatic Cancer: A Systematic Review and Meta-Analysis. [2020]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Equivalent Efficacy but Different Safety Profiles of Gemcitabine Plus Nab-Paclitaxel and FOLFIRINOX in Metastatic Pancreatic Cancer. [2022]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Resection of Locally Advanced Pancreatic Neoplasms after Neoadjuvant Chemotherapy with Nab-Paclitaxel and Gemcitabine following FOLFIRINOX Failure. [2020]

9. England pubmed.ncbi.nlm.nih.gov

Meta-analysis and indirect treatment comparison of modified FOLFIRINOX and gemcitabine plus nab-paclitaxel as first-line chemotherapy in advanced pancreatic cancer. [2022]

10. Canada pubmed.ncbi.nlm.nih.gov

Folfirinox vs. Gemcitabine + Nab-Paclitaxel as the First-Line Treatment for Pancreatic Cancer: A Systematic Review and Meta-Analysis. [2023]

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

Comparative Effectiveness of nab-Paclitaxel Plus Gemcitabine vs FOLFIRINOX in Metastatic Pancreatic Cancer: A Retrospective Nationwide Chart Review in the United States. [2022]

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

Gemcitabine plus nab-paclitaxel versus FOLFIRINOX for unresected pancreatic cancer: Comparative effectiveness and evaluation of tumor growth in Veterans. [2023]