Adaptive Neoadjuvant Chemotherapy for Pancreatic Cancer

(PANC Trial)

Overseen By Medical College of Wisconsin Clinical Cancer Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Medical College of Wisconsin

Disqualifiers: Other cancer, HIV, Hepatitis, 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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

125 Participants Needed

Trial Summary

Do I need to stop taking my current medications for the trial?

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.

What data supports the effectiveness of the drug Gemcitabine with Nab-Paclitaxel for pancreatic cancer?

Research shows that Gemcitabine with Nab-Paclitaxel, when used as a second-line treatment after FOLFIRINOX, can improve survival in patients with advanced pancreatic cancer. Studies have found that these drug combinations are more effective than using Gemcitabine alone. ^{1 2 3 4 5}

Is adaptive neoadjuvant chemotherapy for pancreatic cancer safe for humans?

The safety of treatments like FOLFIRINOX and gemcitabine plus nab-paclitaxel has been studied in pancreatic cancer patients. FOLFIRINOX can cause more severe side effects like neutropenia (low white blood cell count), febrile neutropenia (fever with low white blood cell count), and diarrhea, while gemcitabine plus nab-paclitaxel may lead to anemia and less severe nausea. Both treatments have different safety profiles, so careful monitoring and patient selection are important. ^{6 7 8 9 10}

How is the adaptive neoadjuvant chemotherapy for pancreatic cancer unique?

This treatment is unique because it uses a combination of drugs like FOLFIRINOX and gemcitabine with nab-paclitaxel, which are typically used separately, to potentially improve outcomes by adapting to the patient's response, offering a more personalized approach compared to standard treatments. ^{11 12 13 14 15}

What is the purpose of this trial?

This is an open-label, phase II study in patients with resectable and borderline resectable pancreas cancer.

Research Team

Kathleen Christians, MD

Principal Investigator

Professor

Eligibility Criteria

Adults with confirmed pancreatic adenocarcinoma that's resectable or borderline so, who haven't had extensive prior treatments and are in fairly good health (ECOG <2). They must have certain blood and organ function levels, not be pregnant or breastfeeding, use contraception if of childbearing potential, and can't have HIV/HBV/HCV or other serious conditions.

Inclusion Criteria

My cancer diagnosis was confirmed through a biopsy.

My blood and organ tests meet the required levels for treatment.

I am either not able to have children, using birth control, or have a negative pregnancy test.

Exclusion Criteria

I haven't had a CA19-9 test done before starting chemotherapy when my bilirubin was low.

I have had chemotherapy or radiation in the last 3 years.

Pregnant or breastfeeding patients or any patient with childbearing potential not using contraception four weeks prior to treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemotherapy

Participants receive standard chemotherapy for pancreatic cancer, with treatment response assessed by imaging, biomarkers, and performance status

16 weeks

Regular visits for treatment and assessment

Chemoradiation

Participants receive chemoradiation (50.4 Gy in 28 fractions) if they complete four months of chemotherapy

5-6 weeks

Surgical Resection

Participants are offered surgical resection if there is no local or metastatic disease progression

Follow-up

Participants are monitored for progression-free survival and overall survival

Five years

Treatment Details

Interventions

• Chemoradiation
• First-line Chemotherapy
• Second-line Chemotherapy

Trial Overview This phase II trial is testing how well patients respond to different sequences of chemotherapy and chemoradiation before surgery. It's open-label, meaning everyone knows which treatment they're getting. The goal is to find the best approach for shrinking tumors pre-surgery.

Participant Groups

Group I: Restaging: Response to Treatment Experimental Treatment 1 Intervention

After the first restaging evaluation, further treatment will be based on treatment response. Patients who demonstrate a response \[decline in carbohydrate antigen 19-9 (CA19-9) values\] and radiographic response, along with preserved performance status) will be maintained on the first line chemotherapy for an additional two months.

Group II: Restaging: Patients with Stable Disease Experimental Treatment 1 Intervention

Patients who do not have a significant decline in CA19-9 values will be changed to a second-line therapy for an additional two months.

Group III: Restaging: Local Disease Progression Experimental Treatment 1 Intervention

After the first restaging evaluation, further treatment will be based on treatment response. If, at the initial restaging, the patient has local disease progression amenable to surgical resection, he or she will receive chemoradiation, rather than continued chemotherapy, so the window of opportunity for surgical resection is not lost.

First-line Chemotherapy is already approved in European Union, United States, Japan for the following indications:

Approved in European Union as FOLFIRINOX for:

• Metastatic pancreatic cancer

Approved in United States as FOLFIRINOX for:

• Metastatic pancreatic cancer

Approved in United States as NALIRIFOX for:

• Metastatic pancreatic cancer

Approved in United States as Gemcitabine with Nab-Paclitaxel for:

• Metastatic pancreatic cancer

Approved in Japan as GEM+NPTX for:

• Metastatic pancreatic cancer

Approved in Japan as S-1 for:

• Metastatic pancreatic cancer

Who Is Running the Clinical Trial?

Medical College of Wisconsin

Lead Sponsor

Trials

645

Recruited

1,180,000+

Findings from Research

In a study of 28 patients with advanced pancreatic cancer, the combination of gemcitabine plus nab-paclitaxel (G + Nab-P) after FOLFIRINOX showed a median time to treatment failure of 12 weeks and a median overall survival of 23 weeks, indicating modest efficacy.

The treatment was associated with significant hematologic toxicities, with 25% of patients experiencing anemia and thrombocytopenia, highlighting the need for careful monitoring and further research on optimal dosing and sequencing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine plus nab-paclitaxel for advanced pancreatic cancer after first-line FOLFIRINOX: single institution retrospective review of efficacy and toxicity. Zhang, Y., Hochster, H., Stein, S., 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]

Pancreatic ductal adenocarcinoma (PDAC) is primarily treated with conventional chemotherapy, with gemcitabine/nab-paclitaxel (Gem/NabP) and FOLFIRINOX being the gold standards for first-line treatment, based on 67 trials involving 16,446 patients.

Real-world data shows that the median overall survival for patients treated with FOLFIRINOX is 10.7 months and 9.1 months for Gem/NabP, which aligns closely with results from randomized controlled trials, indicating these treatments are effective options for managing advanced PDAC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two decades of research toward the treatment of locally advanced and metastatic pancreatic cancer: Remarkable effort and limited gain. Yeh, C., Bates, SE.[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 274 pancreatic ductal adenocarcinoma (PDAC) patients, those who showed a significant biochemical response (CA 19-9 decrease ≥50%) after neoadjuvant chemotherapy had better overall survival (OS) and recurrence-free survival compared to those with less response, indicating the importance of monitoring this biomarker.

The study found no significant difference in survival outcomes between patients treated with the two chemotherapy regimens, FOLFIRINOX (FLX) and gemcitabine/nab-paclitaxel (GNP), suggesting that both are equally effective in improving survival rates in PDAC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival Outcomes Associated With Clinical and Pathological Response Following Neoadjuvant FOLFIRINOX or Gemcitabine/Nab-Paclitaxel Chemotherapy in Resected Pancreatic Cancer. Macedo, FI., Ryon, E., Maithel, SK., et al.[2022]

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 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 363 patients with metastatic pancreatic cancer, those treated with FOLFIRINOX (FFX) had a significantly longer median overall survival of 11.3 months compared to 7.0 months for those treated with gemcitabine plus nab-paclitaxel (GN).

Patients receiving FFX also had a longer median time to treatment discontinuation (4.8 months) compared to those on GN (3.4 months), although both groups experienced high rates of dose modifications due to treatment toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical outcomes of first line FOLFIRINOX vs. gemcitabine plus nab-paclitaxel in metastatic pancreatic cancer at the Yale Smilow Hospital System. Patel, T., Miccio, J., Cecchini, M., 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]

FOLFIRINOX, a chemotherapy regimen combining 5-fluorouracil, irinotecan, and oxaliplatin, significantly improves overall survival (11.1 months) and progression-free survival (6.4 months) compared to gemcitabine (6.8 months and 3.3 months, respectively) in patients with metastatic pancreatic cancer, based on a trial with 342 participants.

While FOLFIRINOX is more effective and cost-effective than gemcitabine, it is associated with higher rates of severe side effects, such as neutropenia and diarrhea, necessitating careful patient selection and monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A New Direction for Pancreatic Cancer Treatment: FOLFIRINOX in Context. Kindler, HL.[2020]

In a study of 147 patients with locally advanced pancreatic cancer treated with either gemcitabine/nab-paclitaxel (GN) or FOLFIRINOX (FFX), there were no significant differences in progression-free survival (PFS) or overall survival (OS) between the two treatment groups, with median OS rates of 15.7 months for GN and 16.7 months for FFX.

Both treatment regimens had similar tumor resection rates and independent prognostic factors for survival, indicating that GN and FFX are equally effective as first-line therapies for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine/Nab-Paclitaxel versus FOLFIRINOX in Locally Advanced Pancreatic Cancer: A European Multicenter Study. Williet, N., Petrillo, A., Roth, G., et al.[2021]

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 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 phase II study involving 29 patients with metastatic pancreatic ductal adenocarcinoma (PDAC), the triplet chemotherapy regimen FIr/FOx achieved a promising overall response rate (ORR) of 53%, indicating high efficacy in this difficult-to-treat cancer.

The treatment was generally tolerable, with manageable side effects; however, patients with poorer performance status (PS2) experienced significantly worse overall survival, highlighting the importance of careful patient selection for maintaining safety and treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real life triplet FIr/FOx chemotherapy in first-line metastatic pancreatic ductal adenocarcinoma patients: recommended schedule for expected activity and safety and phase II study. Bruera, G., Massacese, S., Candria, S., et al.[2022]

Neoadjuvant FOLFIRINOX is a cost-effective treatment for borderline resectable/locally advanced pancreatic ductal adenocarcinoma (BR/LA PDAC), showing a higher rate of successful 'R0' resections (84.9%) compared to neoadjuvant gemcitabine plus nab-paclitaxel (G-nP) (81.0%).

Although FOLFIRINOX has higher treatment-related adverse event costs ($10,905.19) compared to G-nP ($4,894.11), it remains the preferred option based on an incremental cost-effectiveness ratio (ICER) of $60,856.47 per quality-adjusted life year (QALY).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness of neoadjuvant FOLFIRINOX versus gemcitabine plus nab-paclitaxel in borderline resectable/locally advanced pancreatic cancer patients. Ingram, MA., Lauren, BN., Pumpalova, Y., et al.[2023]

References

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

Gemcitabine plus nab-paclitaxel for advanced pancreatic cancer after first-line FOLFIRINOX: single institution retrospective review of efficacy and toxicity. [2022]

2. 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]

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

Two decades of research toward the treatment of locally advanced and metastatic pancreatic cancer: Remarkable effort and limited gain. [2023]

4. Italy 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. [2022]

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

Survival Outcomes Associated With Clinical and Pathological Response Following Neoadjuvant FOLFIRINOX or Gemcitabine/Nab-Paclitaxel Chemotherapy in Resected Pancreatic Cancer. [2022]

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

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

7. China pubmed.ncbi.nlm.nih.gov

Multicenter phase II trial of modified FOLFIRINOX in gemcitabine-refractory pancreatic cancer. [2020]

8. China pubmed.ncbi.nlm.nih.gov

Clinical outcomes of first line FOLFIRINOX vs. gemcitabine plus nab-paclitaxel in metastatic pancreatic cancer at the Yale Smilow Hospital System. [2023]

9. 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]

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

A New Direction for Pancreatic Cancer Treatment: FOLFIRINOX in Context. [2020]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Gemcitabine/Nab-Paclitaxel versus FOLFIRINOX in Locally Advanced Pancreatic Cancer: A European Multicenter Study. [2021]

12. 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]

13. 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]

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

Real life triplet FIr/FOx chemotherapy in first-line metastatic pancreatic ductal adenocarcinoma patients: recommended schedule for expected activity and safety and phase II study. [2022]

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

Cost-effectiveness of neoadjuvant FOLFIRINOX versus gemcitabine plus nab-paclitaxel in borderline resectable/locally advanced pancreatic cancer patients. [2023]