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

What You Need to Know Before You Apply

What is the purpose of this trial?

The trial aims to find better treatments for pancreatic cancer by testing different combinations of chemotherapy and radiation. Patients with localized pancreatic cancer, including resectable, borderline resectable, and locally advanced cases, will join various groups. Each group will receive standard chemotherapy for comparison, and researchers may test new treatments against these standards over time. Those with pancreatic adenocarcinoma confirmed by a doctor and no prior chemotherapy or radiation might be suitable candidates. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to advancements in pancreatic cancer care.

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.

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

Research shows that these treatments are generally well-tolerated by patients with pancreatic cancer. Studies on gemcitabine, a common chemotherapy drug, indicate that while some patients experience side effects like tiredness and nerve tingling, these are usually manageable. Nab-paclitaxel, used with gemcitabine, has improved survival rates, though it can cause side effects like low blood cell counts.

Cisplatin and fluorouracil are safe for treating pancreatic cancer but can lead to serious side effects such as low white blood cell counts and stomach issues. Patients treated with irinotecan may experience side effects like diarrhea and vomiting, which require careful monitoring.

Leucovorin often boosts the effect of fluorouracil and is generally safe during treatment. Oxaliplatin, used in combinations like FOLFIRINOX, works well with other drugs but can cause side effects like nerve tingling and sensitivity to cold.

Overall, these drugs have been studied extensively, and their safety profiles are well-documented. Side effects are common but often manageable with medical support. ^{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 combine chemotherapy with radiation therapy, which could enhance the effectiveness of treatment. Unlike standard care options that often rely solely on chemotherapy agents like gemcitabine or FOLFIRINOX, this approach explores the potential benefits of integrating radiation therapy. Additionally, the use of multiple chemotherapy agents like cisplatin, nab-paclitaxel, and irinotecan alongside traditional drugs could offer more comprehensive treatment coverage. This trial aims to determine if these combined treatments can better control the disease and improve outcomes for patients.

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

Studies have shown promising results for the treatments explored in this trial. Participants may receive gemcitabine combined with nab-paclitaxel, which has demonstrated a 31% lower risk of cancer progression or death. Nab-paclitaxel has also improved survival rates for pancreatic cancer patients when used with gemcitabine. Another treatment option is cisplatin, a platinum-containing drug, which has been effective for patients with pancreatic cancer, especially those with certain genetic traits. These treatments have been tested together in various ways, often outperforming single-drug use. This suggests that the combinations tested in the trial could offer potential benefits for patients with pancreatic cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Eugene J. Koay

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7003386/

Efficacy of platinum-based chemotherapy and prognosis ... With platinum-based chemotherapy, the average weighted median OS in patients with HRD was 46.1 and 36.3 months in patients without HRD. Without ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4146684/

Cisplatin in cancer therapy: molecular mechanisms of action In this research, we aim to provide a comprehensive review of the physicochemical properties of cisplatin and related platinum-based drugs, to discuss its uses ...

3. ejcancer.com ejcancer.com/article/S0959-8049(24)00126-6/fulltext

A multicenter, randomized phase 2 study to establish ... Two patients achieved a partial response in arm 1 (ORR 22.2%; none in other arms). Median PFS and OS were 2.4, 2.1, 1.5 and 1.5 months and 6.3, ...

4. mdpi.com mdpi.com/1718-7729/31/9/385

Systemic Therapy for Metastatic Pancreatic Cancer ... This review will focus on the management of advanced pancreatic cancer by examining past and recent clinical trial data

5. bmccancer.biomedcentral.com bmccancer.biomedcentral.com/articles/10.1186/1471-2407-14-471

Chemotherapy regimens for advanced pancreatic cancer This study suggests that some combination therapies may offer greater benefits in the treatment of advanced pancreatic cancer than others.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06095141

Cisplatin to Patients With Pancreatic Cancer and ... The purpose of this study is to evaluate the efficacy of cisplatin based regimen on improving the progression-free survival (PFS) of advanced pancreatic cancer ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4059864/

Systemic treatment for inoperable pancreatic adenocarcinoma The goal of this paper is to provide an update on the key randomized clinical trial data on systemic agents for inoperable pancreatic cancer. The future ...

8. cancer.gov cancer.gov/types/pancreatic/hp/pancreatic-treatment-pdq

Pancreatic Cancer Treatment (PDQ®) - NCI In the gemcitabine-alone group, the most common grade 3 toxicities were neutropenia (27%), fatigue (1%), and neuropathy (1%); febrile ...

9. academic.oup.com academic.oup.com/oncolo/article/30/10/oyaf284/8256689

Phase I study of palbociclib with cisplatin or carboplatin in the ... In conclusion, while the combination of palbociclib with cisplatin or carboplatin showed modest disease stability in patients with advanced PDAC ...

10. ar.iiarjournals.org ar.iiarjournals.org/content/40/7/4011

Safety and Efficacy of Gemcitabine, Docetaxel, ... Conclusion: Second-line PDGX regimen after FOLFIRINOX failure is feasible, with notable toxicity profile and is associated with poor clinical outcomes.