Combined Therapy for Pancreatic Cancer

Recruiting at 9 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

168 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This research study is studying a combination of interventions as a possible treatment for pancreatic tumor. The interventions involved in this study are: * FOLFIRINOX which is made up of 4 different drugs: * 5-Fluorouracil (5-FU) * Oxaliplatin * Irinotecan * Leucovorin * Losartan * Nivolumab * Radiation Therapy * Surgery

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 the combined therapy for pancreatic cancer safe for humans?

The combination of 5-fluorouracil (5-FU), irinotecan, and oxaliplatin has been studied in various trials for pancreatic cancer, showing that while it can be effective, it often comes with significant side effects. Patients in these studies experienced adverse events (unwanted side effects), which sometimes required additional medications to manage. ^{1 2 3 4 5}

What makes the combined therapy for pancreatic cancer unique?

This treatment combines 5-Fluorouracil (5-FU), Irinotecan, Nivolumab, and Oxaliplatin, which is unique because it includes Nivolumab, an immunotherapy drug that helps the immune system fight cancer, alongside the FOLFIRINOX regimen, which is already used for pancreatic cancer. This combination aims to enhance the effectiveness of treatment by using both chemotherapy and immunotherapy. ^{5 6 7 8 9}

What data supports the effectiveness of the drug combination of 5-Fluorouracil, Irinotecan, and Oxaliplatin for pancreatic cancer?

Research shows that the combination of 5-Fluorouracil, Irinotecan, and Oxaliplatin, known as FOLFIRINOX, is used as a treatment for advanced pancreatic cancer, with studies indicating it can be effective, although the response rates are generally less than 32%. ^{1 6 7 10 11}

Who Is on the Research Team?

Theodore S Hong, 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.

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

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

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 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]

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 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]

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]

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]

Citations

1. Switzerland pubmed.ncbi.nlm.nih.gov

5-fluorouracil/leucovorin combined with irinotecan and oxaliplatin (FOLFIRINOX) as second-line chemotherapy in patients with metastatic pancreatic adenocarcinoma. [2022]

2. Greece pubmed.ncbi.nlm.nih.gov

FOLFIRINOX Versus Gemcitabine-based Therapy for Pancreatic Ductal Adenocarcinoma: Lessons from Patient-derived Cell Lines. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Safety and efficacy of S-IROX (S-1, irinotecan and oxaliplatin combination therapy) in patients with advanced pancreatic cancer: A multicenter phase 1b dose-escalation and dose-expansion clinical trial. [2023]

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

Irinotecan plus oxaliplatin and leucovorin-modulated fluorouracil in advanced pancreatic cancer--a Groupe Tumeurs Digestives of the Federation Nationale des Centres de Lutte Contre le Cancer study. [2022]

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

Alterations in Somatic Driver Genes Are Associated with Response to Neoadjuvant FOLFIRINOX in Patients with Localized Pancreatic Ductal Adenocarcinoma. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Modified FOLFIRINOX for Advanced Pancreatic Adenocarcinoma: A UK Single-Centre Experience. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Gemcitabine, oxaliplatin and weekly high-dose 5-FU as 24-h infusion in chemonaive patients with advanced or metastatic pancreatic adenocarcinoma: a multicenter phase II trial of the Arbeitsgemeinschaft Internistische Onkologie (AIO). [2022]

8. England 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. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Oxaliplatin plus irinotecan vs irinotecan as second-line treatment in pancreatic cancer patients: a randomized-controlled open-label Phase II study. [2023]

10. United States 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. [2019]

11. England pubmed.ncbi.nlm.nih.gov

A retrospective study of neoadjuvant FOLFIRINOX in unresectable or borderline-resectable locally advanced pancreatic adenocarcinoma. [2022]