Losartan and Nivolumab in Combination With FOLFIRINOX and SBRT in Localized Pancreatic Cancer

NCT03563248 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 18-179
• Study Type: interventional
• Target: 168
• Locations: 1 country
• Sites: 10

Brief Summary

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

Conditions

Pancreatic Cancer

Keywords

Pancreatic Cancer

Outcome Measures

Primary Outcomes (1)

• Proportion of participants with R0 resection

  R0 resection is defined as microscopically negative margins determined by histopathologic assessment of the resection specimen. The R0 resection rate will be analyzed among all eligible patients, including those not resected due to early progression, death or off-study.

  Up to 8 months after baseline

Secondary Outcomes (4)

• Progression-free survival

  From randomization until the time of progression or death, up to approximately 6 years

• Overall survival

  From randomization until the time of death, up to approximately 6 years

• Pathologic complete response

  Up to 8 months after baseline

• Number of participants with treatment related serious adverse events

  From the start of treatment until 30 days after the end of treatment, up to approximately 14 months

Study Arms (4)

FOLFIRINOX: SBRT: Surgery

ACTIVE COMPARATOR

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

Drug: FOLFIRINOX; Radiation: SBRT; Procedure: Surgery

FOLFIRINOX+Losartan:SBRT+Losartan:Surgery

EXPERIMENTAL

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

Drug: FOLFIRINOX; Drug: Losartan; Radiation: SBRT; Procedure: Surgery

FOLFIRINOX+Losartan:SBRT+Nivolumab+Losartan:Sur

EXPERIMENTAL

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

Drug: FOLFIRINOX; Drug: Losartan; Drug: Nivolumab; Radiation: SBRT; Procedure: Surgery

FOLFIRINOX x 8 : SBRT + Nivolumab : Surgery

EXPERIMENTAL

* 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

Drug: FOLFIRINOX; Drug: Nivolumab; Radiation: SBRT; Procedure: Surgery

Interventions

FOLFIRINOX DRUG

FOLFIRINOX is a combination of 4 chemotherapy agents that may help shrink your tumor before surgery * 5-Fluorouracil (5-FU) - 400 mg/m2 on day one, followed by 1200 mg/m2 by continuous infusion for the subsequent 46-48 hours * Oxaliplatin - 85 mg/m2 by intravenous infusion over 120 minutes on day 1 of each 14 day cycle * Irinotecan - administered at a starting dose of 180 mg/m2 by intravenous infusion over 90 minutes on day 1 of each 14 day cycle * Leucovorin - Administered at a starting dose of 400 mg/m2 over 2 hours on day 1 of each 14 day cycle

FOLFIRINOX x 8 : SBRT + Nivolumab : Surgery; FOLFIRINOX+Losartan:SBRT+Losartan:Surgery; FOLFIRINOX+Losartan:SBRT+Nivolumab+Losartan:Sur; FOLFIRINOX: SBRT: Surgery

Losartan DRUG

Losartan is a drug that is used to lower blood pressure

FOLFIRINOX+Losartan:SBRT+Losartan:Surgery; FOLFIRINOX+Losartan:SBRT+Nivolumab+Losartan:Sur

Nivolumab DRUG

Nivolumab is an antibody that may cause programmed cell death of cancer cells

FOLFIRINOX x 8 : SBRT + Nivolumab : Surgery; FOLFIRINOX+Losartan:SBRT+Nivolumab+Losartan:Sur

SBRT RADIATION

Radiation therapy is believed to increase the likelihood of response of immunotherapy

FOLFIRINOX x 8 : SBRT + Nivolumab : Surgery; FOLFIRINOX+Losartan:SBRT+Losartan:Surgery; FOLFIRINOX+Losartan:SBRT+Nivolumab+Losartan:Sur; FOLFIRINOX: SBRT: Surgery

Surgery PROCEDURE

definitive surgical resection

FOLFIRINOX x 8 : SBRT + Nivolumab : Surgery; FOLFIRINOX+Losartan:SBRT+Losartan:Surgery; FOLFIRINOX+Losartan:SBRT+Nivolumab+Losartan:Sur; FOLFIRINOX: SBRT: Surgery

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed localized pancreatic adenocarcinoma; borderline/potentially resectable or locally advanced.
• Borderline resectable is defined by the NCCN as tumors with venous involvement of the SMV/portal vein demonstrated tumor abutment with or without impingement and narrowing of the lumen, either tumor thrombus or encasement but with suitable vessel proximal and distal to the area of vessel involvement, allowing for safe resection or reconstruction; gastroduodenal artery encasement up to the hepatic artery with either short segment encasement or direct abutment of the hepatic artery, without extension to the celiac axis; or tumor abutment of the SMA not to exceed greater than 180 degrees of the circumference of the vessel wall. Tumors involving retroperitoneal structures that can be surgically removed (i.e. kidney), will also be included.
• Localized is defined as no extrapancreatic disease, no evidence (on CT) of involvement of the celiac axis or SMA, no evidence (CT or MRI) of occlusion of the SMV or SMPV confluence, no evidence of gross peritoneal or distant metastases on staging laparoscopy or laparotomy.
• Locally advanced unresectable disease is defined by the NCCN as: Tumors of the head that have greater than 180 degrees of SMA encasement or any celiac abutment, unreconstructable SMV or portal occlusion, or aortic invasion or encasement. Tumors of the body with SMA or celiac encasement of greater than 180 degrees, unreconstructable SMV or portal occlusion, or aortic invasion. Tumors of the tail with SMA or celiac encasement of greater than 180 degrees. Irrespective of location, all tumors with evidence of nodal metastasis outside of the resection field are deemed unresectable.
• Age \> 18 years
• ECOG performance status 0-1
• Baseline Systolic Blood Pressure (SBP) \> 100 mm Hg. This is based on the average of two values - separate seated, resting measurements taken five minutes apart. BP does not need to be checked in both arms unless a reading is below 110 mm Hg, in which case the other arm can be checked as well. If BP is checked in both arms, the higher value is deemed accurate for calculating the average.
• Normal organ and marrow function as defined below:
• absolute neutrophil count ≥ 1,500/mm3
• platelets ≥ 100,000/mm3
• total bilirubin ≤ 1.5 x institutional upper limit of normal if no biliary stenting has been done OR 2.0 x upper limit of normal if patient is s/p biliary stenting OR two down trending values
• AST(SGOT)/ALT(SGPT) ≤ 2.5 × institutional upper limit of normal
• Potassium (not hemolyzed) \< 5 mmol/L
• creatinine ≤ 1.5 mg/ dL OR
• creatinine clearance ≥ 30 mL/min (as estimated by Cockcroft Gault Equation)

You may not qualify if:

• NOTE: Patients enrolled to the randomized portion of the study (arms 1 thru 3) may not be already treated on ACE or ARB therapy for hypertension or renal protection (with diabetes) at the time of enrollment. If patients are receiving ACE or ARB therapy, they may ONLY be considered for the exploratory arm, Arm 4.
• Serious concomitant systemic disorders incompatible with the study (at the discretion of the investigator), such as significant cardiac or pulmonary morbidity e.g. congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmias not well controlled with medication) or myocardial infarction within the last 12 months, ongoing infection as manifested by fever.
• Pregnant or lactating women. Women of childbearing potential with either a positive or no pregnancy test (serum or urine) at baseline. (Postmenopausal women must have been amenorrheic for at least 12 months to be considered of non-childbearing potential.)
• Any prior chemotherapy, radiation therapy, immunotherapy, or biologic ('targeted') therapy for treatment of the patient's pancreatic tumor
• Treatment for other invasive carcinomas within the last five years who are at greater than 5% risk of recurrence at time of eligibility screening. Carcinoma in-situ and basal cell carcinoma/ squamous cell carcinoma of the skin are allowed.
• Lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome
• Known, existing uncontrolled coagulopathy
• Prior systemic fluoropyrimidine therapy within the past 10 years. Prior topical fluoropyrimidine use is allowed. Prior unanticipated severe reaction to fluoropyrimidine therapy, or known hypersensitivity to 5-fluorouracil or known DPD deficiency.
• Participation in any investigational drug study within 4 weeks preceding the start of study treatment
• History of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant, precluding informed consent, or interfering with compliance or oral drug intake.
• Major surgery, excluding laparoscopy, within 4 weeks of the start of study treatment, without complete recovery
• Concomitant use of cimetidine, as it can decrease the clearance of 5-FU. Another H2-blocker or proton pump inhibitor may be substituted before study entry
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to 5-fluorouracil, irinotecan, oxaliplatin, or losartan
• Other serious medical conditions that the investigator feels might compromise study participation
• An active, known or suspected autoimmune disease other than those listed below. Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Bristol-Myers Squibb: collaborator
• Stand Up To Cancer: collaborator
• Lustgarten Foundation: collaborator

Study Sites (10)

University of Colorado Cancer Center

Aurora, Colorado, 80045, United States

Location

Sibley Memorial Hospital

Washington D.C., District of Columbia, 20016, United States

Location

The Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02215, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Newton Wellesley Hospital

Newton, Massachusetts, 02462, United States

Location

New York University Langone Medical Center

New York, New York, 10016, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Wang H, Yuan S, Wang H. Current Status of Research on Losartan in Tumour Therapy. J Cell Mol Med. 2026 Jan;30(1):e70985. doi: 10.1111/jcmm.70985.

  PMID: 41486497 DERIVED

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

folfirinox; Losartan; Nivolumab; Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrazoles; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Jennifer Y. Wo, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 7, 2018
• First Posted: June 20, 2018
• Study Start: August 10, 2018
• Primary Completion: February 16, 2022
• Study Completion (Estimated): April 1, 2027
• Last Updated: October 1, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (10)