Neoadjuvant Chemotherapy for Pancreatic Cancer

(PANCREAS Trial)

Overseen By Leyo Ruo, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Hamilton Health Sciences Corporation

Disqualifiers: Metastatic disease, Cardiac disease, Neuropathy, 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: 12

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of two chemotherapy treatments, mFOLFIRINOX and gemcitabine/nab-paclitaxel, for individuals with a specific type of pancreatic cancer that is nearly removable by surgery. The main goal is to determine if these treatments can shrink the cancer enough to make surgery a safe option. Suitable candidates for this trial have been diagnosed with borderline resectable pancreatic cancer and are healthy enough for surgery. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that combining gemcitabine and nab-paclitaxel is a common treatment for pancreatic cancer. Studies have assessed their safety and effectiveness. While effective, serious side effects have been reported, particularly in older patients. These side effects include low blood counts, fatigue, and an increased risk of infections.

Studies have also examined mFOLFIRINOX, a modified drug combination for pancreatic cancer. Although potent, it can cause side effects such as fatigue, nausea, and diarrhea. Despite these, some researchers consider it safer than the standard version.

Both treatments are generally tolerated for pancreatic cancer, but they can cause significant side effects. Discussing potential implications with a doctor is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for pancreatic cancer because they aim to improve outcomes with existing chemotherapy regimens in a new way. While the standard approach often involves gemcitabine alone, this trial tests gemcitabine combined with nab-paclitaxel, and another regimen called mFOLFIRINOX. These combinations are designed to be more potent against cancer cells. Additionally, the trial incorporates a re-staging CT scan with a CA 19-9 serum test to closely monitor the cancer's response, which could lead to more personalized treatment plans. By integrating these elements, researchers hope to increase the effectiveness of pre-surgery chemotherapy and improve long-term survival rates.

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

This trial will evaluate the effectiveness of two chemotherapy regimens for pancreatic cancer: gemcitabine with nab-paclitaxel and mFOLFIRINOX. Studies have shown that gemcitabine with nab-paclitaxel can extend patient survival to an average of 12 to 30 months, which is significant for this aggressive cancer. This treatment is considered safe and can improve outcomes, making surgeries easier for patients. Meanwhile, mFOLFIRINOX has demonstrated a 37.1% response rate, with patients who complete it living up to 46.2 months on average. Both treatments in this trial have been linked to better survival rates and may offer improved outcomes for those with pancreatic cancer that is difficult to remove surgically. ^{6 7 8 9 10}

Who Is on the Research Team?

Leyo Ruo, MD

Principal Investigator

McMaster University

Are You a Good Fit for This Trial?

This trial is for men and women aged 18-79 with borderline resectable pancreatic adenocarcinoma, who can consent to treatment and are fit for surgery. They must have good organ function and performance status (ECOG ≤1). Excluded are those with prior pancreas radiation, substance abuse issues, pregnancy, metastatic disease, serious heart conditions, chemotherapy contraindications, ongoing infections or pre-existing neuropathy.

Inclusion Criteria

Able to provide written informed consent

My blood counts and liver/kidney functions are within normal ranges.

I am 79 years old or younger.

Exclusion Criteria

I have a history of serious heart conditions.

Illegal substance abuse, or social conditions that may interfere with patient's participation in the trial

I am currently fighting an infection in my body.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Chemotherapy

Participants receive 6 cycles (three months) of IV combination chemotherapy with mFOLFIRINOX or gemcitabine/nab-paclitaxel

3 months

6 visits (in-person)

Re-staging and Surgery Preparation

Re-staging CT scan with CA 19-9 serum test and optional staging laparoscopy

4 weeks

Pancreatectomy

Surgical resection of the pancreas 4 weeks following the last day of chemotherapy

1 week

Adjuvant Chemotherapy

Participants receive adjuvant chemotherapy as per standard of care

Varies

Follow-up

Participants are monitored every four months with a CT scan of the chest/abdomen for two years after resection or until evidence of disease recurrence

24 months

6 visits (in-person)

Long-term Follow-up

Follow-up of patients every six months for up to 5 years following the initiation of treatment

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Gemcitabine / Nab-paclitaxel
• mFOLFIRINOX
• Stereotactic body radiation therapy

Trial Overview

The study tests the effectiveness of neoadjuvant chemotherapy using mFOLFIRINOX or gemcitabine/nab-paclitaxel in patients before they undergo pancreatectomy. It's a single-arm feasibility trial focused on individuals with borderline resectable pancreatic cancer at a single center.

How Is the Trial Designed?

Group I: Single Arm Intervention Experimental Treatment 2 Interventions

1. Chemotherapy: 6 cycles (three months) of IV combination chemotherapy with mFOLFIRINOX on day 1 followed by one week of rest (14-day cycle). Alternatively, patients will receive three months of gemcitabine / nab-paclitaxel. 2. Re-staging CT scan with Carbohydrate Antigen (CA) 19-9 serum test. 3. Staging laparoscopy to rule out occult metastatic disease is optional based on surgeon's preference. 5\. Pancreatectomy 4 weeks following the last day of Chemotherapy as per standard of care. 6\. Adjuvant chemotherapy: as per standard of care. 7. Clinical assessment and CT scan with CA 19-9 serum test at 4-month intervals until identification of cancer recurrence. 8\. Follow up of patients after 2 years every six months for up to 5 years following the initiation of treatment will be performed off-protocol as per standard of care.

Gemcitabine / Nab-paclitaxel is already approved in United States, European Union for the following indications:

Approved in United States as Gemcitabine / Nab-paclitaxel for:

• Metastatic pancreatic adenocarcinoma

Approved in European Union as Gemcitabine / Nab-paclitaxel for:

• Metastatic pancreatic adenocarcinoma

Who Is Running the Clinical Trial?

Hamilton Health Sciences Corporation

Lead Sponsor

Trials

380

Recruited

345,000+

Published Research Related to This Trial

In a phase II trial involving 48 patients with gemcitabine-refractory unresectable pancreatic cancer, modified FOLFIRINOX demonstrated promising efficacy with an objective response rate of 18.8% and a disease control rate of 62.5%.

The treatment was associated with manageable safety concerns, primarily neutropenia (64.6% of patients), but most non-hematologic adverse events were mild, indicating that while effective, careful monitoring for hematologic toxicities is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter phase II trial of modified FOLFIRINOX in gemcitabine-refractory pancreatic cancer. Chung, MJ., Kang, H., Kim, HG., et al.[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]

Recent treatment regimens for advanced pancreatic cancer, including gemcitabine, FOLFIRINOX, and nab-paclitaxel, have shown varying levels of efficacy, highlighting the importance of understanding their unique safety profiles.

Nurses play a crucial role in patient education and symptom management, as each treatment regimen has different adverse events that need to be identified and managed effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nursing Implications of Chemotherapy Agents and Their Associated Side Effects in Patients With Pancreatic Cancer. Hronek, JW., Reed, M.[2017]

In a study of 54 patients with advanced pancreatic cancer, S-IROX showed a higher disease control rate (73.7%) compared to modified FOLFIRINOX (mFFX) (62.2%), indicating it may be more effective as a second-line treatment after gemcitabine plus nab-paclitaxel.

Both S-IROX and mFFX had similar overall survival rates (14.2 months for S-IROX and 11.5 months for mFFX) and tolerability, with no significant differences in severe side effects, suggesting both regimens are viable options for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A retrospective comparative study of S-IROX and modified FOLFIRINOX for patients with advanced pancreatic cancer refractory to gemcitabine plus nab-paclitaxel. Saito, K., Nakai, Y., Takahara, N., et al.[2022]

Modified FOLFIRINOX (mFOLFIRINOX) showed moderate efficacy in treating locally advanced or metastatic pancreatic cancer, with a response rate of 30.8% and a disease control rate of 69.2% in 13 patients after previous treatments failed.

The treatment was associated with a median overall survival of 176 days and significant adverse effects, including neutropenia in 38.5% of patients, indicating that while mFOLFIRINOX can be beneficial, it also carries risks that need to be managed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modified FOLFIRINOX for Locally Advanced and Metastatic Pancreatic Cancer Patients Resistant to Gemcitabine and S-1 in Japan: A Single Institutional Experience. Umemura, A., Nitta, H., Sasaki, A., 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 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]

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 the NAPOLI 3 study involving 770 patients with metastatic pancreatic ductal adenocarcinoma, the NALIRIFOX treatment regimen resulted in a median overall survival of 11.1 months, which was significantly longer than the 9.2 months observed with the nab-paclitaxel and gemcitabine combination.

Both treatment groups experienced a high rate of grade 3 or higher adverse events (87% for NALIRIFOX and 86% for nab-paclitaxel-gemcitabine), indicating that while NALIRIFOX may improve survival, it does not significantly increase the risk of severe side effects compared to the standard treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NALIRIFOX versus nab-paclitaxel and gemcitabine in treatment-naive patients with metastatic pancreatic ductal adenocarcinoma (NAPOLI 3): a randomised, open-label, phase 3 trial. Wainberg, ZA., Melisi, D., Macarulla, T., et al.[2023]

In a meta-analysis of eight studies, Folfirinox demonstrated higher rates of surgical resection and R0 resection, as well as improved progression-free survival (PFS) and overall survival (OS) compared to gemcitabine plus nab-paclitaxel (GNP) for patients with borderline resectable or locally advanced pancreatic cancer.

Importantly, Folfirinox did not lead to an increase in severe toxicity rates compared to GNP, suggesting it is a safer option while providing better efficacy in treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of neoadjuvant Folfirinox and Gemcitabine plus Nab-Paclitaxel for borderline resectable and locally advanced pancreatic cancer: a systematic review and meta-analysis. Dong, LP., Liu, YM., Lu, WJ., et al.[2022]

In a study of 568 patients with metastatic pancreatic cancer, gemcitabine combined with nab-paclitaxel (GnP) showed a higher disease control rate (82.6%) compared to modified FOLFIRINOX (mFFX) (67.9%), indicating better effectiveness in managing the disease.

Patients receiving mFFX experienced significantly more severe nonhematologic side effects, such as grade 3/4 anorexia and diarrhea, suggesting that GnP may be a safer option with fewer severe adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Treatment Outcomes Between Gemcitabine With Nab-Paclitaxel and Modified FOLFIRINOX for First-Line Chemotherapy in Metastatic and Recurrent Pancreatic Cancer: Propensity Score Matching. Mie, T., Sasaki, T., Takeda, T., et al.[2023]

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