Chemotherapy + Radiation Therapy for Pancreatic Cancer

Overseen By Eugene J. Koay

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Immunosuppressives

Disqualifiers: Active malignancy, Cardiac arrhythmias, Congestive heart failure, HIV, 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: 3-6 months

105 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a phase II study using the Bayesian platform design. There are three clinical stage groups of localized pancreatic cancer: resectable, borderline resectable, and locally advanced disease. Each stage group will have a defined standard of care chemotherapy regimen for a control arm, serving as a basis of comparison. Each group may have one or more experimental arms. Experimental arms may be added to the platform over time, and the effects of the experimental treatments will be tested against the controls for each group.

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

The trial requires that you do not use immunosuppressive medications. Other medications are not specifically mentioned, so it's best to discuss your current medications with the study team to ensure they are acceptable.

What data supports the effectiveness of the chemotherapy drugs used in this treatment for pancreatic cancer?

Research shows that combinations like FOLFIRINOX (which includes fluorouracil, leucovorin, irinotecan, and oxaliplatin) and gemcitabine plus nab-paclitaxel improve survival in patients with advanced pancreatic cancer compared to using gemcitabine alone. ^{1 2 3 4 5}

Is nab-paclitaxel safe for use in cancer treatment?

Nab-paclitaxel, a formulation of paclitaxel, has been shown to have a better safety profile with fewer side effects compared to traditional paclitaxel. It is approved for use in several cancers, including pancreatic cancer, and is associated with fewer adverse effects like myelosuppression (low blood cell counts) and nausea. ^{6 7 8 9 10}

What makes the chemotherapy and radiation therapy treatment for pancreatic cancer unique?

This treatment combines multiple chemotherapy drugs, including cisplatin, fluorouracil, gemcitabine, and others, with radiation therapy, which is not a standard approach for pancreatic cancer. The combination aims to enhance the effectiveness of treatment by using different mechanisms to attack cancer cells, potentially improving outcomes compared to using chemotherapy alone. ^{1 3 11 12 13}

Research Team

Eugene J. Koay

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

Adults with resectable, borderline resectable, or locally advanced pancreatic cancer. Must not be pregnant/nursing and have a life expectancy over 6 months. Eligible participants need normal organ function (blood counts, liver/kidney tests within certain limits) and no prior treatments for those treatment-naive or only specific past chemotherapies for the previously treated.

Inclusion Criteria

Previously Treated Resectable PDAC Cohort: Creatinine =< 1.5 x upper limit of normal (ULN)

My white blood cell count is high enough for treatment.

My kidneys work well enough (creatinine clearance over 45 mL/min).

Exclusion Criteria

I do not have serious heart rhythm problems.

I have a cancer other than basal cell carcinoma that hasn't been treated yet.

My pancreatic cancer was not just in the pancreas when diagnosed.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive chemotherapy regimens such as mFOLFIRINOX, gemcitabine, and others for 3 to 6 months depending on the group, with possible radiation therapy

3-6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

16 weeks

Long-term follow-up

Participants are followed up every 16 weeks to assess overall survival and progression-free survival

Up to 5 years

Treatment Details

Interventions

• Cisplatin
• Fluorouracil
• Gemcitabine
• Irinotecan
• Leucovorin
• Nab-paclitaxel
• Oxaliplatin
• Radiation Therapy

Trial Overview The PIONEER-Panc study is testing various chemotherapy drugs (Cisplatin, Irinotecan, Oxaliplatin, Leucovorin, Fluorouracil) and Nab-paclitaxel plus Gemcitabine against standard care in different stages of pancreatic cancer using a phase II Bayesian platform design to determine their effectiveness.

Participant Groups

Group I: Control arm GroupI(mFOLFIRINOX) Active Control 4 Interventions

Patients receive mFOLFIRINOX for 3 months before and after surgery in the absence of disease progression or unacceptable toxicity.

Group II: Control arm GroupII(chemotherapy, FOLFIRINOX) Active Control 7 Interventions

Patients receive gemcitabine, gemcitabine and nab-paclitaxel, gemcitabine and cisplatin, or FOLFIRINOX for up to 4 months in the absence of disease progression or unacceptable toxicity.

Group III: Control arm GroupIII(FOLFIRINOX, radiation therapy) Active Control 5 Interventions

Patients receive FOLFIRINOX for 4-6 months in the absence of disease progression or unacceptable toxicity. Patients may then undergo radiation therapy at the discretion of medical doctors.

Group IV: Control arm GroupVI(chemotherapy,FOLFIRINOX,radiation therapy) Active Control 8 Interventions

Patients receive gemcitabine, gemcitabine and nab-paclitaxel, gemcitabine and cisplatin, or FOLFIRINOX for 6 months in the absence of disease progression or unacceptable toxicity. Patients may then undergo radiation therapy at the discretion of medical doctors

Group V: Control arm GroupIV(chemotherapy,FOLFIRINOX,radiation therapy) Active Control 8 Interventions

Patients receive gemcitabine, gemcitabine and nab-paclitaxel, gemcitabine and cisplatin, or FOLFIRINOX for 6 months in the absence of disease progression or unacceptable toxicity. Patients may then undergo radiation therapy at the discretion of medical doctors.

Group VI: Control arm GroupV(FOLFIRINOX, radiation therapy) Active Control 5 Interventions

Patients receive FOLFIRINOX for 4-6 months in the absence of disease progression or unacceptable toxicity. Patients may then undergo radiation therapy at the discretion of medical doctors

Cisplatin is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in United States as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Canada as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Japan as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a study of 485 patients with localized pancreatic cancer, those treated with FOLFIRINOX showed higher rates of partial response according to RECIST criteria compared to those treated with gemcitabine plus nab-paclitaxel (GA), indicating better initial tumor response.

Despite the higher response rates and more frequent surgeries (pancreatectomy) in the FOLFIRINOX group, overall survival rates were similar between the two treatment regimens, suggesting that while FOLFIRINOX may be more effective in shrinking tumors, it does not necessarily lead to longer survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Response and Survival Associated With First-line FOLFIRINOX vs Gemcitabine and nab-Paclitaxel Chemotherapy for Localized Pancreatic Ductal Adenocarcinoma. Perri, G., Prakash, L., Qiao, W., 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 78 patients with non-small cell lung cancer, treatment with nano-albumin paclitaxel combined with cisplatin resulted in a significantly higher disease control rate of 79.49% compared to 38.46% for traditional paclitaxel combined with cisplatin after four treatment cycles.

The nano-albumin regimen also showed a lower incidence of adverse reactions, such as myelosuppression, nausea, vomiting, and hyperglycemia, indicating it is both effective and safer for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of Clinical Efficacy of Nano-Albumin Paclitaxel Treatment for Advanced Cell Lung Cancer. Li, X., Zhang, Y., Zhi, X., et al.[2022]

Nab-paclitaxel, a novel formulation of paclitaxel, is water-soluble and free from toxic solvents, leading to reduced infusion-related toxicities and allowing for higher dosing compared to traditional formulations.

Clinical trials have shown that nab-paclitaxel improves overall response rates and survival outcomes while exhibiting a superior safety profile in patients with gastrointestinal cancers, leading to its FDA approval for use in metastatic pancreatic cancer and other gastrointestinal malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nab-Paclitaxel in the Treatment of Gastrointestinal Cancers-Improvements in Clinical Efficacy and Safety. Hassan, MS., Awasthi, N., Ponna, S., et al.[2023]

Paclitaxel (TAXOL) is an effective chemotherapy drug that works by disrupting microtubule function, showing significant activity against advanced ovarian, breast, and non-small cell lung cancers, among others.

With proper premedication, the incidence of hypersensitivity reactions to paclitaxel has been reduced to 3%, although neutropenia remains a major dose-limiting side effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Paclitaxel (Taxol)]. Hájek, R.[2015]

Gemcitabine remains the standard treatment for advanced pancreatic cancer, but combination therapies with other chemotherapeutic agents have shown improved response rates without significantly extending survival, based on recent phase III trials.

Research is ongoing into novel therapies that target specific molecular pathways in pancreatic cancer cells, suggesting that future treatments may combine traditional chemotherapy with these new targeted approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of systemic therapy for advanced pancreatic cancer. El-Rayes, BF., Philip, PA.[2007]

References

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

Response and Survival Associated With First-line FOLFIRINOX vs Gemcitabine and nab-Paclitaxel Chemotherapy for Localized Pancreatic Ductal Adenocarcinoma. [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. Japan pubmed.ncbi.nlm.nih.gov

A multicenter propensity score analysis of FOLFIRINOX vs gemcitabine plus nab-paclitaxel administered to patients with metastatic pancreatic cancer: results from the NAPOLEON study. [2021]

4. Greece pubmed.ncbi.nlm.nih.gov

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

5. Netherlands pubmed.ncbi.nlm.nih.gov

Nab-paclitaxel plus gemcitabine versus nab-paclitaxel plus gemcitabine followed by FOLFIRINOX induction chemotherapy in locally advanced pancreatic cancer (NEOLAP-AIO-PAK-0113): a multicentre, randomised, phase 2 trial. [2022]

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

Analysis of Clinical Efficacy of Nano-Albumin Paclitaxel Treatment for Advanced Cell Lung Cancer. [2022]

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

Nab-Paclitaxel in the Treatment of Gastrointestinal Cancers-Improvements in Clinical Efficacy and Safety. [2023]

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

Toxicity of Nab-Paclitaxel Compared to Paclitaxel in a Tertiary Hospital in Jeddah, Saudi Arabia: A Retrospective Cohort Study. [2023]

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

Efficacy of albumin-bound paclitaxel combined with nedaplatin in neoadjuvant therapy for esophageal squamous cell carcinoma: A single-center retrospective observational study. [2023]

10. Czech Republic pubmed.ncbi.nlm.nih.gov

[Paclitaxel (Taxol)]. [2015]

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

A review of systemic therapy for advanced pancreatic cancer. [2007]

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

Effect of a MUC5AC Antibody (NPC-1C) Administered With Second-Line Gemcitabine and Nab-Paclitaxel on the Survival of Patients With Advanced Pancreatic Ductal Adenocarcinoma: A Randomized Clinical Trial. [2023]

13. England pubmed.ncbi.nlm.nih.gov

Systemic therapy for advanced pancreatic cancer. [2022]