Chemotherapy for Pancreatic Cancer

(PASS-01 Trial)

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two chemotherapy treatments for pancreatic ductal adenocarcinoma that has spread. It compares modified folfirinox (also known as FOLFOXIRI or FOIL) with gemcitabine/nab-paclitaxel to determine which is more effective. Participants must have an untreated diagnosis of metastatic pancreatic cancer and be able to undergo a tumor biopsy. The trial includes lab work to explore the treatments' molecular effects on the cancer. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

A previous study identified FOLFIRINOX as a common treatment for advanced pancreatic cancer. While generally safe, some patients reported serious digestive issues, with 4.2% experiencing severe problems. Research has shown that a combination of gemcitabine and nab-paclitaxel is also frequently used for pancreatic cancer. Studies have found it can extend patient survival, though it may cause side effects like tiredness and low blood cell counts.

Both treatments are standard options and have been used safely in many patients. However, as with any chemotherapy, there are risks of side effects. Discussing these with a doctor is always advisable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they offer distinct approaches to tackling pancreatic cancer. Modified FOLFIRINOX combines four drugs—Folinic acid, 5-Fluorouracil, Irinotecan, and Oxaliplatin—administered intravenously, which may enhance effectiveness through a synergistic effect. Meanwhile, Gemcitabine/nab-Paclitaxel, also given intravenously, is notable for its use of nab-Paclitaxel, a nanoparticle albumin-bound formulation that may improve drug delivery to cancer cells. Both treatments are standard care options, but their unique drug combinations and delivery methods provide hope for potentially improved outcomes in pancreatic cancer treatment.

What evidence suggests that this trial's treatments could be effective for pancreatic cancer?

In this trial, participants will receive either modified FOLFIRINOX or gemcitabine combined with nab-paclitaxel, both effective for advanced pancreatic cancer. Research has shown that patients using FOLFIRINOX live for about 11.1 months on average, longer than the 6.8 months with traditional gemcitabine treatment, and it reduces tumor size in 47.8% of patients. Adding nab-paclitaxel to gemcitabine has also improved patient survival and delayed cancer progression, reducing tumor size in 17.2% of patients and enhancing survival chances. Both treatments offer hope in extending the lives of those facing this challenging disease. ^{2 5 6 7 8}

Who Is on the Research Team?

Elizabeth Jaffee, MD

Principal Investigator

Johns Hopkins University

Jennifer J Knox, MD

Principal Investigator

University Health Network, Toronto

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

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 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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7081111/

FOLFOXIRI vs FOLFIRINOX as first-line chemotherapy in ... Detailed outcomes data are summarized in Table 2. The objective response rate was 47.8% in the FOLFIRINOX group, compared to 37.1% in the ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6320053/

Clinical outcomes of FOLFIRINOX in locally advanced ... About 1/3rd of patients with pancreatic cancers display unresectable localized disease, and the median overall survival (OS) is approximately 9 to 12 months for ...

3. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2795978

Five-Year Outcomes of FOLFIRINOX vs Gemcitabine as ... This randomized clinical trial examines 5-year outcomes and prognostic factors for overall survival for treatment with modified FOLFIRINOX ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa1011923

FOLFIRINOX versus Gemcitabine for Metastatic Pancreatic ... Results. The median overall survival was 11.1 months in the FOLFIRINOX group as compared with 6.8 months in the gemcitabine group (hazard ratio for death, 0.57; ...

5. annalsofoncology.org annalsofoncology.org/article/S0923-7534(19)33892-X/fulltext

Effectiveness and costs of FOLFIRINOX in the treatment ... Median overall survival was 9,87 months (CI 95%: 8,378- 11,362 months). Time till progression was 6.41 months (range: 0,67- 20,27 months). The rate of ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9087258/

Efficacy and safety of FOLFIRINOX as second-line ... FOLFIRINOX is recommended as a second-line chemotherapy regimen for patients with pancreatic cancer that have failed on gemcitabine-based first-line therapy.

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e16393

Efficacy and safety of FOLFIRINOX versus gemcitabine- ... Efficacy and safety of FOLFIRINOX versus gemcitabine-based regimens for treatment of metastatic pancreatic cancer: A systematic review and meta-analysis.

8. annalsofoncology.org annalsofoncology.org/article/S0923-7534(19)46893-2/fulltext

Safety and efficacy of modified FOLFIRINOX in patients ... Background: FOLFIRINOX (FFX) has been regarded as one of the standard treatments for patients with metastatic pancreatic cancer (MPC).