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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a combination of chemotherapy (modified FOLFIRINOX) and targeted radiotherapy (Stereotactic Body Radiation Therapy, SBRT) can better control pancreatic cancer that remains localized to the pancreas but is not easily removable by surgery. The focus is on extending the time patients live without the cancer worsening, compared to traditional treatments. Ideal participants are those diagnosed with pancreatic cancer that hasn't spread to other organs, have not received prior cancer treatments, and can receive care at the Smilow New Haven campus. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

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.

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

Previous studies have shown that modified FOLFIRINOX (mFOLFIRINOX) is safer than the standard version, reducing serious side effects like decreased bone marrow activity and fatigue. However, some patients still experienced significant issues, such as vomiting and diarrhea.

Research indicates that the safety of stereotactic body radiotherapy (SBRT) can vary. Some studies reported serious side effects in up to 34% of patients, but these rates are similar to those of other treatments. SBRT might also control tumors better with less harm compared to traditional radiation methods.

Both treatments have demonstrated some serious side effects, but they are generally considered safe enough for further testing. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about combining mFOLFIRINOX with stereotactic body radiotherapy (SBRT) for pancreatic cancer because it brings a new approach to treatment. Unlike the standard chemotherapy regimens, mFOLFIRINOX followed by SBRT aims to enhance precision in attacking cancer cells while sparing healthy tissue. This combo could improve outcomes by targeting the tumor more effectively and potentially reducing side effects. By integrating advanced radiation techniques, this approach offers hope for more effective management of a difficult-to-treat cancer.

What evidence suggests that mFOLFIRINOX followed by SBRT could be an effective treatment for pancreatic cancer?

Research shows that a treatment called modified FOLFIRINOX can extend the lives of people with pancreatic cancer. Studies have found it significantly improves survival compared to gemcitabine, another common treatment. Patients with locally advanced pancreatic cancer have tolerated this treatment well and achieved good results.

For stereotactic body radiotherapy (SBRT), evidence suggests it effectively controls the disease and causes fewer side effects than traditional radiation. Some studies have linked SBRT to a median survival time of 13 to 14 months. In this trial, participants will receive mFOLFIRINOX followed by SBRT, which may enhance outcomes for people with certain types of pancreatic cancer. ^{1 2 4 6 7}

Who Is on the Research Team?

Kimberly Johung, MD, PhD

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10873666/

Stereotactic body radiotherapy for pancreatic cancer Results showed a median OS of 14 months, along with an excellent LC rate of 85 % at one year. The efficacy of combining immunotherapy with radiation in the ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0167814025052144

Long-Term outcomes of ablative stereotactic body radiation ... The early study reported poor outcomes with mOS of 5.7 months and a 1-year OS of 5 %, and grade ≥ 2 GI toxicity was observed in 79 % of ...

3. redjournal.org redjournal.org/article/S0360-3016(25)03704-6/fulltext

LINAC-based Stereotactic Ablative Radiotherapy (SABR) ... We retrospectively reviewed treatment characteristics and outcomes of pancreatic cancer patients who received SABR (50 Gy/30 Gy in five biweekly ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9599229/

Stereotactic Body Radiotherapy (SBRT) of Pancreatic Cancer ... SBRT achieved similar disease control outcomes as IMRT but with less toxicity. In another study conducted by Ryal et al. [35], the median OS was 13 months from ...

5. ro-journal.biomedcentral.com ro-journal.biomedcentral.com/articles/10.1186/s13014-018-1138-3

Stereotactic ablative radiotherapy (SABR) as primary ... SABR offers an alternative treatment for pancreatic cancer, with the potential for improved tumour control and reduced toxicity compared with conventional ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT07173374

Stereotactic Centralized Ablative Radiotherapy for Locally ... Pancreatic cancer is among the most aggressive malignancies and is associated with poor prognosis. The 5-year survival rate remains below 10%, and most patients ...

7. advancesradonc.org advancesradonc.org/article/S2452-1094(20)30159-7/pdf

Ablative Five-Fraction Stereotactic Body Radiation Therapy ... Pancreatic tumor resectability status was determined by multidisciplinary tumor board consensus after review of radiographic imaging and patient operability ...