Combined Therapy for Pancreatic Cancer

Not currently recruiting at 10 trial locations

Overseen By Theodore S Hong, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Massachusetts General Hospital

Must not be taking: ACE inhibitors, ARBs, Cimetidine

Disqualifiers: Pregnancy, Prior chemotherapy, Cardiac disorders, Autoimmune 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

Compensation: Varies

Number of Visits: 8

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new combination of treatments for pancreatic cancer. Researchers aim to determine how drugs, radiation, and surgery might shrink pancreatic tumors. The treatments being tested include FOLFIRINOX (a combination of four drugs, including 5-Fluorouracil, Irinotecan, and Oxaliplatin), Losartan, Nivolumab, and radiation therapy, with some participants also undergoing surgery. Individuals with a specific type of pancreatic cancer that hasn't spread may be suitable candidates. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but if you are on ACE or ARB therapy for hypertension or renal protection, you may only be eligible for a specific part of the study. Additionally, you cannot use cimetidine, as it affects one of the trial drugs.

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

Research shows that FOLFIRINOX, a mix of four chemotherapy drugs, can help treat pancreatic cancer, but it often causes strong side effects. Studies have found it to be more toxic than some other treatments. Common side effects include fatigue, low blood cell counts, and digestive problems.

When combined with losartan, a blood pressure medication, FOLFIRINOX might lead to better results in some cases. Although more research is needed, some studies suggest that patients tolerate this combination well.

Nivolumab, a drug that boosts the immune system, has been tested with FOLFIRINOX for pancreatic cancer. The combination was generally tolerable, with side effects like fatigue and digestive issues, but most patients managed them well.

Researchers continue to study these treatments to better understand their safety. Joining trials like this can help gather more information about the safety and effectiveness of these treatments. ^{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 multiple therapeutic approaches that could enhance effectiveness. The treatments use FOLFIRINOX, a chemotherapy regimen, paired with stereotactic body radiation therapy (SBRT) and nivolumab, an immunotherapy drug, which is not a typical combination in standard care. Some experimental arms also include losartan, a blood pressure medication, which may improve drug delivery to tumors. This multi-pronged strategy aims to attack the cancer from several angles, potentially improving outcomes compared to traditional treatments like chemotherapy alone.

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

Studies have shown that FOLFIRINOX effectively treats pancreatic cancer. For patients with metastatic pancreatic cancer, FOLFIRINOX increased average survival from 6.8 months to 11.1 months compared to gemcitabine. In this trial, one arm will test FOLFIRINOX combined with losartan, which has been shown to shrink tumors and potentially improve surgical outcomes. Another arm will add nivolumab, an immune therapy, to existing treatments, which has been linked to longer survival in patients who have already responded well to chemotherapy. These findings suggest that combining these treatments could be promising for pancreatic cancer treatment. ^{2 5 6 7 8}

Who Is on the Research Team?

Jennifer Y. Wo, MD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

This trial is for adults over 18 with localized pancreatic adenocarcinoma that's potentially resectable or advanced. Participants must have stable blood pressure, normal organ/marrow function, and an ECOG status of 0-1. Women should use contraception; those pregnant or breastfeeding are excluded. People can't join if they've had certain allergic reactions, severe infections like TB, HIV/AIDS, uncontrolled health issues, recent major surgery without recovery, prior treatments for their tumor or live vaccines within a month.

Inclusion Criteria

I am older than 18 years.

My pancreatic cancer is confirmed and may be operable or advanced but not spread.

Your blood pressure is higher than 100 mm Hg when the study starts.

Exclusion Criteria

I am allergic to certain chemotherapy drugs or losartan.

I had major surgery less than 4 weeks ago and haven't fully recovered.

Participation in any investigational drug study within 4 weeks preceding the start of study treatment

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemotherapy

Participants receive FOLFIRINOX regimen every 14 days for 8 cycles

16 weeks

8 visits (in-person)

Radiation

SBRT is administered 2-6 weeks after completing chemotherapy, with concurrent Nivolumab

2-6 weeks

Surgery

Participants undergo an attempt at definitive surgical resection following SBRT

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 months

What Are the Treatments Tested in This Trial?

Interventions

• 5-Fluorouracil (5-FU)
• Irinotecan
• Losartan
• Nivolumab
• Oxaliplatin
• SBRT
• Surgery

Trial Overview The study tests a combination treatment for pancreatic cancer including FOLFIRINOX (a mix of four drugs), Losartan (a blood pressure medication), Nivolumab (an immunotherapy drug), radiation therapy and surgery to see how well they work together in treating the tumor.

How Is the Trial Designed?

Group I: FOLFIRINOX+Losartan:SBRT+Nivolumab+Losartan:Sur Experimental Treatment 5 Interventions

The FOLFIRINOX regimen will be administered intravenously. Treatment will be every 14 days +3/ -1 at physician discretion * Losartan will be administered orally as a tablet to be taken by the patient at home every day * SBRT should be administered 2-6 weeks after completing chemotherapy * Participants will receive nivolumab during SBRT * All participants will undergo an attempt at definitive surgical resection following SBRT

Group II: FOLFIRINOX+Losartan:SBRT+Losartan:Surgery Experimental Treatment 4 Interventions

The FOLFIRINOX regimen will be administered intravenously. Treatment will be every 14 days +3/ -1 at physician discretion * Losartan will be administered orally as a tablet to be taken by the patient at home every day * SBRT should be administered 2-6 weeks after completing chemotherapy * All participants will undergo an attempt at definitive surgical resection following SBRT

Group III: FOLFIRINOX x 8 : SBRT + Nivolumab : Surgery Experimental Treatment 4 Interventions

* The FOLFIRINOX regimen will be administered intravenously. Treatment will be every 14 days +3/ -1 at physician discretion * SBRT should be administered 2-6 weeks after completing chemotherapy * Participants will receive nivolumab during SBRT * All participants will undergo an attempt at definitive surgical resection following SBRT

Group IV: FOLFIRINOX: SBRT: Surgery Active Control 3 Interventions

The FOLFIRINOX regimen will be administered intravenously. Treatment will be every 14 days +3/ -1 at physician discretion * SBRT should be administered 2-6 weeks after completing chemotherapy * All participants will undergo an attempt at definitive surgical resection following SBRT

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Stand Up To Cancer

Collaborator

Trials

53

Recruited

40,100+

Lustgarten Foundation

Collaborator

Trials

27

Recruited

5,500+

Published Research Related to This Trial

In a study of 18 patients with locally advanced pancreatic cancer (LAPC), neoadjuvant therapy using FOLFIRINOX resulted in a promising R0 resection rate of 44%, indicating that a significant portion of patients became eligible for surgical removal of their tumors after treatment.

The treatment showed high efficacy with a 1-year overall survival rate of 100% and a progression-free survival rate of 83%, although it was associated with notable chemotherapy-related toxicities, including neutropenia and fatigue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A retrospective study of neoadjuvant FOLFIRINOX in unresectable or borderline-resectable locally advanced pancreatic adenocarcinoma. Hosein, PJ., Macintyre, J., Kawamura, C., et al.[2022]

In a study of 196 patients with localized pancreatic ductal adenocarcinoma (PDAC) treated with neoadjuvant FOLFIRINOX, alterations in the SMAD4 gene were linked to a significantly lower rate of surgical resection (27.8% vs 59.4%) and a higher risk of developing metastatic disease during treatment.

While common alterations in KRAS and TP53 were observed, no specific somatic alterations were associated with major pathologic response, highlighting the potential role of SMAD4 as a biomarker for treatment response and the need for alternative therapies for patients with these alterations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alterations in Somatic Driver Genes Are Associated with Response to Neoadjuvant FOLFIRINOX in Patients with Localized Pancreatic Ductal Adenocarcinoma. Ecker, BL., Court, CM., Janssen, QP., et al.[2023]

The introduction of newer chemotherapy regimens, FOLFIRINOX and gemcitabine/nab-paclitaxel, led to a significant improvement in overall survival for patients with metastatic pancreatic cancer, with median survival increasing from 8.97 months to 9.95 months between the years 2006-2010 and 2011-2015.

Despite the overall improvement in survival rates, African American patients experienced worse outcomes, indicating a disparity in treatment effectiveness, with a hazard ratio of 1.63 for death compared to Caucasian patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes in Patients With Metastatic Pancreatic Adenocarcinoma With the Introduction of New Chemotherapeutic Drugs: 10-Year Experience of a Single NCI-designated Comprehensive Cancer Center. Zhang, KJ., Dyson, G., Gatz, JL., et al.[2019]

The modified FOLFIRINOX (mFOLFIRINOX) regimen showed a tolerable safety profile with lower hematological toxicity compared to the full-dose FOLFIRINOX, while still maintaining comparable efficacy in treating advanced pancreatic ductal adenocarcinoma (PDAC).

In a study of 18 patients, 80% achieved at least stable disease, with a median overall survival of 9.3 months and progression-free survival of 7.2 months, indicating that mFOLFIRINOX can be an effective treatment option for fit patients with advanced PDAC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Modified FOLFIRINOX for Advanced Pancreatic Adenocarcinoma: A UK Single-Centre Experience. Ghorani, E., Wong, HH., Hewitt, C., et al.[2023]

In a study of 825 patients with metastatic pancreatic ductal adenocarcinoma receiving second-line chemotherapy, those treated with liposomal irinotecan-based regimens experienced the lowest rates of severe blood-related adverse events like anemia, neutropenia, and thrombocytopenia compared to other regimens such as FOLFIRINOX and FOLFOX.

Patients on liposomal irinotecan also required similar or fewer medications to manage these adverse events, indicating a potentially safer and more manageable treatment option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world safety and supportive care use of second-line 5-fluorouracil-based regimens among patients with metastatic pancreatic ductal adenocarcinoma. Kim, G., Cockrum, P., Surinach, A., et al.[2023]

In a study of 19 patient-derived pancreatic cancer cell lines, FOLFIRINOX showed optimal sensitivity in six cell lines, while three cell lines responded better to gemcitabine plus nab-paclitaxel (Gem-Pac), indicating that different regimens may work better for different patients.

The findings suggest that understanding the specific sensitivity of cancer cells to these treatments could help identify biomarkers, which may guide personalized chemotherapy choices for patients with pancreatic ductal adenocarcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FOLFIRINOX Versus Gemcitabine-based Therapy for Pancreatic Ductal Adenocarcinoma: Lessons from Patient-derived Cell Lines. Begg, SKS., Birnbaum, DJ., Clark, JW., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38319559/

Real Life Data and Outcome of FOLFIRINOX Use in ... Conclusion: Survival rates for patient with metastatic pancreatic cancer treated with FOLFIRINOX were worse in our study population than in comparative studies.

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa1011923

FOLFIRINOX versus Gemcitabine for Metastatic Pancreatic ... In this study, FOLFIRINOX was an effective first-line treatment option for patients with metastatic pancreatic adenocarcinoma and good ECOG performance status.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3816713/

Outcomes with FOLFIRINOX for Borderline Resectable and ... A randomized trial of FOLFIRINOX versus gemcitabine in metastatic pancreatic cancer showed improved median survival from 6.8 to 11.1 months[25]. Further studies ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1470204516001728

Articles FOLFIRINOX for locally advanced pancreatic cancer Patients with locally advanced pancreatic cancer treated with FOLFIRINOX had a median overall survival of 24·2 months—longer than that reported with gemcitabine ...

5. annalsofoncology.org annalsofoncology.org/article/S0923-7534(19)33892-X/fulltext

Effectiveness and costs of FOLFIRINOX in the treatment ... Median overall survival was 9,87 months (CI 95%: 8,378- 11,362 months). Time till progression was 6.41 months (range: 0,67- 20,27 months). The rate of ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9087258/

Efficacy and safety of FOLFIRINOX as second-line ... FOLFIRINOX is recommended as a second-line chemotherapy regimen for patients with pancreatic cancer that have failed on gemcitabine-based first-line therapy.

7. jgo.amegroups.org jgo.amegroups.org/article/view/20784/html

Retrospective comparison of the efficacy and the toxicity of ... In this study, the overall response rate was 31.6%; median PFS and median OS were 6.8 and 11.1 months, respectively. Additionally, a retrospective Canadian ...

8. jhoponline.com jhoponline.com/issue-archive/2022-issues/march-2022-vol-12-special-feature/the-safety-of-folfirinox-regimen-oxaliplatin-and-irinotecan-sequence-of-administration

The Safety of FOLFIRINOX Regimen: Oxaliplatin and ... The primary objective was to determine if the sequencing of oxaliplatin and irinotecan has an impact on the incidence of adverse reactions.