Adaptive Neoadjuvant Chemotherapy for Pancreatic Cancer

(PANCREAS Trial)

Recruiting at 1 trial location

Overseen By Medical College of Wisconsin Cancer Center Clinical Trials Office

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Medical College of Wisconsin

Disqualifiers: Chemotherapy, Radiation, Other malignancy, 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

87 Participants Needed

Trial Summary

What is the purpose of this trial?

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

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

The trial protocol does not specify whether you need to stop taking your current medications. It's best to discuss your specific medications with the trial team to get a clear answer.

What data supports the effectiveness of the drug regimen Gemcitabine/Nab-paclitaxel and mFOLFIRINOX for pancreatic cancer?

Research shows that Gemcitabine/nab-paclitaxel and FOLFIRINOX improve survival in patients with advanced pancreatic cancer compared to using Gemcitabine alone. These treatments have demonstrated increased survival rates and delayed tumor progression in clinical trials. ^{1 2 3 4 5}

Is the adaptive neoadjuvant chemotherapy for pancreatic cancer safe?

The treatments Gemcitabine/Nab-paclitaxel and FOLFIRINOX have been used in patients with advanced pancreatic cancer and have shown manageable toxicities. However, higher rates of adverse events were noted with FOLFIRINOX compared to Gemcitabine/Nab-paclitaxel. ^{1 2 4 6 7}

What makes the Adaptive Neoadjuvant Chemotherapy for Pancreatic Cancer treatment unique?

This treatment is unique because it uses a combination of gemcitabine/nab-paclitaxel and mFOLFIRINOX in a sequential manner, which may help overcome resistance to initial therapy and delay tumor progression in pancreatic cancer. ^{1 2 5 6 8}

Research Team

Kathleen Christians, MD

Principal Investigator

Medical College of Wisconsin

Eligibility Criteria

This trial is for adults with resectable or borderline resectable pancreatic cancer. Participants must have confirmed adenocarcinoma, an ECOG performance status less than 2 (meaning they are able to carry out all self-care but unable to carry out any work activities), and adequate organ/bone marrow function. They need a CA19-9 level above 35 mg/dL and must understand the study well enough to give informed consent.

Inclusion Criteria

My organs and bone marrow are functioning well.

My cancer diagnosis was confirmed through a biopsy.

I am suspected to have pancreatic cancer and agree to additional biopsies.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Subtype Diagnosis and Classification

Patients are classified by molecular subtype using the PurIST classifier into basal and classical pancreatic cancer groups

1 week

Neoadjuvant Chemotherapy

Patients receive chemotherapy based on their subtype: mFOLFIRINOX for classical subtype and Gemcitabine/Nab-paclitaxel for basal subtype

8 weeks

Restaging and Treatment Adjustment

Patients are restaged to assess treatment response and adjust therapy accordingly, including potential switch to chemoradiation or second-line therapy

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Treatment Details

Interventions

• Gemcitabine/Nab-paclitaxel Treatment Regimen
• mFOLFIRINOX Treatment Regimen

Trial Overview The study tests two chemotherapy regimens: mFOLFIRINOX and Gemcitabine/Nab-paclitaxel, along with chemoradiation in patients with operable pancreatic cancer. It's a phase II trial where doctors will adapt treatment based on RNA expression profiles from biopsy samples taken through endoscopic ultrasound (EUS).

Participant Groups

Group I: Subtype diagnosis and classification: Classical Experimental Treatment 1 Intervention

Patients will be classified by (molecular) subtype (using the PurIST classifier) into two groups: basal and classical pancreatic cancer. Patients in the classical group will receive two months of the mFOLFIRINOX Treatment Regimen.

Group II: Subtype diagnosis and classification: Basal Experimental Treatment 1 Intervention

Patients will be classified by (molecular) subtype (using the PurIST classifier) into two groups: basal and classical pancreatic cancer. Upon diagnosis, patients categorized as basal will receive two months of the Gemcitabine/Nab-paclitaxel Treatment Regimen.

Group III: Classical Group: 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 IV: Classical Group: 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 V: Classical Group: Restaging: Local Disease Progression Experimental Treatment 1 Intervention

Further treatment will be based on treatment response. If 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.

Group VI: Basal Group: 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 VII: Basal Group: 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 VIII: Basal Group: Restaging: Local Disease Progression Experimental Treatment 1 Intervention

Further treatment will be based on treatment response. If 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.

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

Approved in United States as Gemzar/Abraxane for:

• Metastatic pancreatic adenocarcinoma

Approved in European Union as Gemzar/Abraxane for:

• Metastatic pancreatic adenocarcinoma

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 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]

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]

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]

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]

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 comparing two treatments for metastatic pancreatic cancer, modified gemcitabine plus nab-paclitaxel (G/nab-P) showed a median overall survival (OS) of 9.4 months, while mFOLFIRINOX had an OS of 7.5 months, although this difference was not statistically significant (p = 0.16).

mFOLFIRINOX was associated with higher rates of adverse events compared to G/nab-P, indicating that while both treatments had similar efficacy in terms of OS, mFOLFIRINOX may pose greater risks to patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line gemcitabine plus nab-paclitaxel versus FOLFIRINOX for metastatic pancreatic cancer in a real-world population. Hatashima, A., Arango, MJ., Reardon, J., et al.[2023]

A retrospective analysis of 59 patients with advanced refractory pancreatic cancer showed that the combination of nab-paclitaxel and gemcitabine (AG) is active as a second-line or beyond treatment, with 10% achieving a partial response and 47% having stable disease.

The median overall survival was 3.9 months and progression-free survival was 3 months, with toxicity levels similar to those reported in the earlier MPACT trial, indicating that AG has manageable side effects in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The nab-paclitaxel/gemcitabine regimen for patients with refractory advanced pancreatic adenocarcinoma. Palacio, S., Hosein, PJ., Reis, I., et al.[2020]

A patient with metastatic pancreatic adenocarcinoma showed a remarkable response to three different gemcitabine-based chemotherapy regimens over a period of 2 years, highlighting the potential for effective treatment despite the cancer's known chemoresistance.

The chemotherapy regimens included GEMOX, GTX, and gemcitabine with nab-paclitaxel, demonstrating that multiple lines of treatment can lead to significant clinical and radiographic improvements in pancreatic cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinically meaningful responses to sequential gemcitabine-based chemotherapy regimens in a patient with metastatic pancreatic cancer. Klimant, E., Markman, M., Albu, DM.[2021]

References

1. United States 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. [2022]

2. 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]

3. 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]

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

Nursing Implications of Chemotherapy Agents and Their Associated Side Effects in Patients With Pancreatic Cancer. [2017]

5. 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]

6. England pubmed.ncbi.nlm.nih.gov

First-line gemcitabine plus nab-paclitaxel versus FOLFIRINOX for metastatic pancreatic cancer in a real-world population. [2023]

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

The nab-paclitaxel/gemcitabine regimen for patients with refractory advanced pancreatic adenocarcinoma. [2020]

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

Clinically meaningful responses to sequential gemcitabine-based chemotherapy regimens in a patient with metastatic pancreatic cancer. [2021]