Chemotherapy + SBRT for Pancreatic Cancer

Overseen By Kimberly Johung, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Yale University

Must not be taking: Oxaliplatin, Irinotecan, Fluorouracil, Capecitabine

Disqualifiers: Other malignancy, Cardiac disease, 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

Duration: 9 months

28 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, since no prior treatment for pancreatic cancer is allowed, you may need to stop any cancer-related medications.

What data supports the effectiveness of the treatment mFOLFIRINOX combined with SBRT for pancreatic cancer?

Research shows that the modified FOLFIRINOX (mFOLFIRINOX) regimen improves survival rates in patients with advanced pancreatic cancer compared to other treatments, although it can have significant side effects. Additionally, using mFOLFIRINOX before surgery in patients with locally advanced pancreatic cancer has been associated with better outcomes. ^{1 2 3 4 5}

Is the combination of chemotherapy and SBRT generally safe for humans?

The modified FOLFIRINOX chemotherapy regimen, used for pancreatic cancer, has shown an acceptable safety profile with common side effects like low white blood cell counts, fever, and digestive issues. No treatment-related deaths were reported, indicating it is generally safe for humans. ^{1 2 6 7 8}

How does the drug mFOLFIRINOX differ from other treatments for pancreatic cancer?

mFOLFIRINOX is a modified version of the FOLFIRINOX chemotherapy regimen, which is used as a first-line treatment for advanced pancreatic cancer. It is unique because it combines four drugs (fluorouracil, leucovorin, irinotecan, and oxaliplatin) and is adjusted to reduce toxicity while maintaining effectiveness, making it more tolerable for patients compared to the standard FOLFIRINOX. ^{1 2 3 4 9}

What is the purpose of this trial?

The purpose of this study is to evaluate the efficacy of modified FOLFIRINOX followed by stereotactic body radiotherapy (SBRT) in patients with borderline resectable pancreatic cancer (BRPC) and locally advanced pancreatic cancer (LAPC). The primary hypothesis will be to determine if modified FOLFIRINOX followed by SBRT improves progression free survival (PFS) compared to historical controls treated with gemcitabine-based chemotherapy with or without standard fractionated radiation.

Research Team

Kimberly Johung, MD, PhD

Principal Investigator

Yale University

Eligibility Criteria

This trial is for adults with non-metastatic, unresectable pancreatic adenocarcinoma who haven't had prior treatments. They should be in good physical condition (ECOG 0-1), not pregnant or nursing, and have adequate blood counts and organ function. Those with recent heart issues, other cancers within five years (with some exceptions), or significant lung disease can't participate.

Inclusion Criteria

I have not received any treatment for pancreatic cancer.

My pancreatic cancer is at a stage where surgery might be possible.

I do not have severe numbness or pain in my hands or feet.

Exclusion Criteria

Failing to meet any of the Inclusion Criteria

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive modified FOLFIRINOX followed by stereotactic body radiotherapy (SBRT)

9 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including progression-free survival and recurrence rates

Up to 3 years

Treatment Details

Interventions

• mFOLFIRINOX
• Stereotactic body radiotherapy (SBRT)

Trial Overview The study tests if a chemotherapy combo called modified FOLFIRINOX followed by targeted radiation therapy (SBRT) can improve the time patients live without their cancer getting worse compared to previous standard treatments. It's specifically for those with borderline resectable or locally advanced pancreatic cancer.

Participant Groups

Group I: mFOLFIRINOX followed by SBRT Experimental Treatment 2 Interventions

Patients will receive mFOLFIRINOX, followed stereotactic body radiotherapy (SBRT).

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

Approved in European Union as mFOLFIRINOX for:

• Pancreatic ductal adenocarcinoma (PDAC)

Approved in United States as mFOLFIRINOX for:

• Advanced pancreatic cancer

Approved in Canada as mFOLFIRINOX for:

• Resectable pancreatic ductal adenocarcinoma

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

Findings from Research

Modified-dose FOLFIRINOX (mFOLFIRINOX) demonstrated comparable efficacy to standard-dose FOLFIRINOX (sFOLFIRINOX) in treating pancreatic cancer, with similar objective response rates and overall survival outcomes among 130 patients studied.

mFOLFIRINOX was associated with significantly lower rates of severe adverse events, such as neutropenia, anorexia, and diarrhea, suggesting it is a safer option for patients who may be concerned about toxicity while maintaining effective treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of efficacy and safety between standard-dose and modified-dose FOLFIRINOX as a first-line treatment of pancreatic cancer. Kang, H., Jo, JH., Lee, HS., et al.[2022]

The modified FOLFIRINOX (mFOLFIRINOX) regimen demonstrated a high treatment efficacy in patients with locally advanced pancreatic cancer (LAPC) and metastatic pancreatic cancer (MPC), achieving a response rate of 55.2% among 29 evaluable patients.

The treatment was well-tolerated, with only 9 patients experiencing grade 3 or 4 adverse effects, and no patients discontinued treatment due to side effects, indicating a favorable safety profile for this regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Modified FOLFIRINOX for advanced pancreatic cancer: a tertiary center experience from China]. Bai, X., Su, R., Ma, T., et al.[2018]

The modified FOLFIRINOX regimen is effective and well-tolerated for patients with advanced nonmetastatic pancreatic cancer, showing a high rate of surgical resection (72% attempted, 51.1% accomplished) with manageable toxicity, primarily diarrhea in 14% of patients.

Patients who underwent surgical resection after treatment with mFOLFIRINOX experienced a median progression-free survival of 18 months, significantly longer than the 8 months for those who did not have surgery, indicating a potential survival benefit from this approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant modified (m) FOLFIRINOX for locally advanced unresectable (LAPC) and borderline resectable (BRPC) adenocarcinoma of the pancreas. Blazer, M., Wu, C., Goldberg, RM., et al.[2022]

In a study of 198 patients with advanced pancreatic cancer, the SOXIRI chemotherapy regimen showed similar overall survival (12.1 months) and progression-free survival (6.5 months) compared to the standard mFOLFIRINOX regimen (11.2 months and 6.8 months, respectively), indicating comparable efficacy.

While both regimens had similar safety profiles, SOXIRI was associated with a higher incidence of anemia (41.4% vs. 24%), suggesting that while effective, it may have specific side effects that need to be monitored.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of SOXIRI versus mFOLFIRINOX in advanced pancreatic cancer. Li, X., Huang, J., Wang, F., et al.[2023]

Modified-FOLFIRINOX (mFOLFIRINOX) significantly improves safety and tolerability for Chinese patients with locally advanced pancreatic cancer (LAPC), with a response rate of 37.1% and common severe side effects including neutropenia and anemia.

Patients with LAPC who received neoadjuvant therapy with mFOLFIRINOX and subsequently underwent surgery had a median overall survival of 27.7 months, which is significantly better than the 8.9 months seen in patients who had upfront surgery without prior chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of Modified-FOLFIRINOX-Regimen-Based Neoadjuvant Therapy with Outcomes of Locally Advanced Pancreatic Cancer in Chinese Population. Li, X., Guo, C., Li, Q., et al.[2023]

In a study of 243 patients with advanced pancreatic adenocarcinoma treated with FOLFIRINOX, the relative dose intensity (RDI) of the treatment agents did not significantly correlate with disease control or objective response, suggesting that dose reductions may not compromise treatment effectiveness.

The median cumulative multi-drug RDI was 80%, and including RDI in predictive models did not enhance the ability to forecast disease control, indicating that oncologists can safely adjust doses without fearing a loss of therapeutic benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FOLFIRINOX relative dose intensity and disease control in advanced pancreatic adenocarcinoma. Vary, A., Lebellec, L., Di Fiore, F., et al.[2022]

In a multicenter phase II study involving 31 chemotherapy-naïve Japanese patients with advanced pancreatic cancer, the modified FOLFIRINOX (mFX) regimen showed a response rate of 38.7% and a median overall survival of 14.9 months, indicating its efficacy as a first-line treatment.

While mFX resulted in fewer Grade 3 or 4 non-hematological adverse events compared to the standard FOLFIRINOX regimen, it still had a high incidence of hematological adverse events, particularly neutropenia (83.9%), suggesting the need for further optimization to enhance safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multicenter prospective phase II study of first-line modified FOLFIRINOX for unresectable advanced pancreatic cancer. Yoshida, K., Iwashita, T., Uemura, S., et al.[2022]

In a phase II study involving 36 chemotherapy-naïve Japanese patients with metastatic pancreatic cancer, the FOLFIRINOX regimen demonstrated a response rate of 38.9% and a median overall survival of 10.7 months, indicating its efficacy in this population.

The treatment was associated with significant toxicities, including high rates of neutropenia (77.8%) and febrile neutropenia (22.2%), but no treatment-related deaths were reported, suggesting that while FOLFIRINOX is effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of FOLFIRINOX for chemotherapy-naïve Japanese patients with metastatic pancreatic cancer. Okusaka, T., Ikeda, M., Fukutomi, A., et al.[2022]

In a study of 15 patients with advanced biliary tract cancer who had not responded to previous chemotherapy, the modified FOLFIRINOX (mFOLFIRINOX) regimen showed promising efficacy, with a 26.7% objective response rate and an 80% disease control rate.

The treatment was well-tolerated, with a median overall survival of 13.2 months and manageable side effects, primarily grade 3/4 neutropenia, indicating that mFOLFIRINOX could be a viable salvage therapy option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of modified FOLFIRINOX as salvage therapy for patients with refractory advanced biliary tract cancer: a retrospective study. Ye, LF., Ren, C., Bai, L., et al.[2022]

References

1. China pubmed.ncbi.nlm.nih.gov

Comparison of efficacy and safety between standard-dose and modified-dose FOLFIRINOX as a first-line treatment of pancreatic cancer. [2022]

2. China pubmed.ncbi.nlm.nih.gov

[Modified FOLFIRINOX for advanced pancreatic cancer: a tertiary center experience from China]. [2018]

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

Neoadjuvant modified (m) FOLFIRINOX for locally advanced unresectable (LAPC) and borderline resectable (BRPC) adenocarcinoma of the pancreas. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of SOXIRI versus mFOLFIRINOX in advanced pancreatic cancer. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Association of Modified-FOLFIRINOX-Regimen-Based Neoadjuvant Therapy with Outcomes of Locally Advanced Pancreatic Cancer in Chinese Population. [2023]

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

FOLFIRINOX relative dose intensity and disease control in advanced pancreatic adenocarcinoma. [2022]

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

A multicenter prospective phase II study of first-line modified FOLFIRINOX for unresectable advanced pancreatic cancer. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Phase II study of FOLFIRINOX for chemotherapy-naïve Japanese patients with metastatic pancreatic cancer. [2022]

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

Efficacy and safety of modified FOLFIRINOX as salvage therapy for patients with refractory advanced biliary tract cancer: a retrospective study. [2022]