Nivolumab in Combination With Chemotherapy Pre-Surgery in Treating Patients With Borderline Resectable Pancreatic Cancer

NCT03970252 | Completed Early Phase 1 DMC FDA Drug

• 2 other identifiers: 19-000290NCI-2019-02886
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

This pilot and feasibility study studies how well nivolumab and combination chemotherapy work before surgery in treating patients with pancreatic cancer that could possibly be removed by surgery. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body?s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as fluorouracil, irinotecan hydrochloride, leucovorin calcium and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving nivolumab in combination with chemotherapy before surgery may work better in treating patients with pancreatic cancer compared to chemotherapy alone.

Conditions

Borderline Resectable Pancreatic Adenocarcinoma; Resectable Pancreatic Ductal Adenocarcinoma

Outcome Measures

Primary Outcomes (2)

• Clinically relevant pancreatic fistula in the post-operative period after neoadjuvant treatment with nivolumab and fluorouracil, irinotecan hydrochloride, leucovorin calcium and oxaliplatin (FOLFIRINOX) (mFFX) chemotherapy

  Descriptive statistics with frequency and proportion will be used.

  Up to 3 years

• Pathologic complete response after nivolumab and mFFX treatment

  Descriptive statistics with frequency and proportion will be used.

  Up to 3 years

Secondary Outcomes (8)

• Percent change of CA 19-9 response rate

  Baseline up to 3 years

• R0 resection rate

  Up to 3 years

• Overall response rate (ORR)

  Up to 3 years

• Disease free survival (DFS)

  Up to 3 years

• Incidence of adverse events

  Up to 28 days after last dose of study drug

Other Outcomes (2)

• Changes in immune cell infiltrates and cancer cell IFNgamma signaling in response to FOLFIRINOX and nivolumab treatment

  Baseline up to 3 years

• Signaling and metabolomic changes in pancreatic ductal adenocarcinoma (PDAC) cancer cells that respond to IFNgamma

  Baseline up to 3 years

Study Arms (1)

Treatment (nivolumab, mFOLFIRINOX)

EXPERIMENTAL

Patients receive nivolumab IV over 60 minutes on day 1. Patients also receive fluorouracil IV over 10 minutes and over 46 hours, irinotecan hydrochloride IV over 90-120 minutes, leucovorin calcium IV over 120 minutes, and oxaliplatin IV over 120 minutes on days 1 and 15. Treatments repeat every 28 days for 3-6 cycles in the absence of disease progression or unacceptable toxicity. Within 2-4 weeks after treatment, patients with resectable disease undergo surgery. Within 8-12 weeks after surgery, patients with successful resection may receive 6 additional cycles of fluorouracil, irinotecan hydrochloride, leucovorin calcium, and oxaliplatin in the absence of disease progression or unacceptable toxicity.

Drug: Fluorouracil; Drug: Irinotecan; Drug: Irinotecan Hydrochloride; Drug: Leucovorin; Drug: Leucovorin Calcium; Biological: Nivolumab; Drug: Oxaliplatin; Procedure: Therapeutic Conventional Surgery

Interventions

Fluorouracil DRUG

Given IV

Also known as: 5-Fluoro-2,4(1H, 3H)-pyrimidinedione, 5-Fluorouracil, 5-Fluracil, 5-FU, AccuSite, Carac, Fluoro Uracil, Fluouracil, Flurablastin, Fluracedyl, Fluracil, Fluril, Fluroblastin, Ribofluor, Ro 2-9757, Ro-2-9757

Treatment (nivolumab, mFOLFIRINOX)

Irinotecan DRUG

Given IV

Treatment (nivolumab, mFOLFIRINOX)

Irinotecan Hydrochloride DRUG

Given IV

Also known as: Campto, Camptosar, Camptothecin 11, Camptothecin-11, CPT 11, CPT-11, Irinomedac, U-101440E

Treatment (nivolumab, mFOLFIRINOX)

Leucovorin DRUG

Given IV

Also known as: Folinic acid

Treatment (nivolumab, mFOLFIRINOX)

Leucovorin Calcium DRUG

Given IV

Also known as: Adinepar, Calcifolin, Calcium (6S)-Folinate, Calcium Folinate, Calcium Leucovorin, Calfolex, Calinat, Cehafolin, Citofolin, Citrec, citrovorum factor, Cromatonbic Folinico, Dalisol, Disintox, Divical, Ecofol, Emovis, Factor, Citrovorum, Flynoken A, Folaren, Folaxin, FOLI-cell, Foliben, Folidan, Folidar, Folinac, Folinate Calcium, folinic acid, Folinic Acid Calcium Salt Pentahydrate, Folinoral, Folinvit, Foliplus, Folix, Imo, Lederfolat, Lederfolin, Leucosar, leucovorin, Rescufolin, Rescuvolin, Tonofolin, Wellcovorin

Treatment (nivolumab, mFOLFIRINOX)

Nivolumab BIOLOGICAL

Given IV

Also known as: BMS-936558, MDX-1106, NIVO, ONO-4538, Opdivo

Treatment (nivolumab, mFOLFIRINOX)

Oxaliplatin DRUG

Given IV

Also known as: 1-OHP, Ai Heng, Aiheng, Dacotin, Dacplat, Diaminocyclohexane Oxalatoplatinum, Eloxatin, Eloxatine, JM-83, Oxalatoplatin, Oxalatoplatinum, RP 54780, RP-54780, SR-96669

Treatment (nivolumab, mFOLFIRINOX)

Therapeutic Conventional Surgery PROCEDURE

Undergo surgery

Treatment (nivolumab, mFOLFIRINOX)

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed pancreatic adenocarcinoma
• One of the following:
• Borderline resectable disease. There are multiple definitions of borderline resectable pancreatic ductal adenocarcinoma (PDAC) including the MD Anderson definition and the criteria developed during the Consensus Conference sponsored by the American Hepato-Pancreato-Biliary Association, Society of Surgical Oncology, and Society for Surgery of the Alimentary Tract. Borderline resectable PDAC cases will be identified per the definition developed in the currently running inter-group pilot trial for borderline resectable pancreatic cancer (NCT01821612). Per this trial, borderline resectable PDAC is defined as the presence of any one or more of the following on computed tomography (CT):
• An interface between the primary tumor and the superior mesenteric vein or portal vein (SMV-PV) measuring \>= 180 degrees of the circumference of the vessel wall
• Short-segment occlusion of the SMV-PV with normal vein above and below the level of obstruction that is amenable to resection and venous reconstruction
• Short segment interface (of any degree) between tumor and hepatic artery with normal artery proximal and distal to the interface that is amenable to resection and reconstruction
• An interface between the tumor and superior mesenteric artery (SMA) measuring \< 180 degrees of the circumference of the vessel wall
• Performance status of Eastern Cooperative Oncology Group (ECOG) of 0-1
• Therapy naive
• Absolute neutrophil count (ANC) \>= 1500/mm\^3
• Platelets \>= 100,000/mm\^3
• Hemoglobin \>= 9 g/dl
• Serum total bilirubin =\< 1.5 x upper limit of normal (ULN)
• Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) and aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]) =\< 2.5 x ULN
• Alkaline phosphatase =\< 2.5 x ULN

You may not qualify if:

• Locally advanced (clearly unresectable) or metastatic disease
• Known status of human immunodeficiency virus (HIV) which is not well-controlled at the time of study eligibility
• Untreated hepatitis B infection
• Active infection or antibiotics within 48 hours prior to study
• Currently active second primary malignancy or history of malignancy less than 5 years prior to the time of study eligibility (patients with history of skin cancers excluding melanoma will be eligible for participation)
• Serious medical comorbidities such as New York Heart Association class III/IV cardiac disease, uncontrolled cardiac arrhythmias, myocardial infarction over the past 12 months
• Known, existing uncontrolled coagulopathy. Patients who have had a venous thromboembolic event (e.g., pulmonary embolism or deep vein thrombosis) requiring anticoagulation are eligible IF: they are appropriately anticoagulated and have not had a grade 2 or greater bleeding episode in the 3 weeks before day 1
• Prior history of cerebrovascular accident or transient ischemic attack, or pre-existing carotid artery disease
• Known pregnancy, nursing women or positive pregnancy test. Requirement for women of childbearing potential (WOCBP) must have a pregnancy test every 4 weeks and WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin \[HCG\]) within 24 hours prior to the start of nivolumab
• Any prisoners, or subjects who are compulsory detained are excluded
• Any condition that would preclude informed consent, consistent follow-up and compliance for the study participation

Sponsors & Collaborators

• Jonsson Comprehensive Cancer Center: lead
• Bristol-Myers Squibb: collaborator
• NovoCure Ltd.: collaborator

Study Sites (1)

UCLA / Jonsson Comprehensive Cancer Center

Los Angeles, California, 90095, United States

Location

MeSH Terms

Interventions

Fluorouracil; dehydroftorafur; Irinotecan; Leucovorin; Nivolumab; Oxaliplatin

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Camptothecin; Alkaloids; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Coordination Complexes; Organic Chemicals

Study Officials

• Zev A Wainberg

  UCLA / Jonsson Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 29, 2019
• First Posted: May 31, 2019
• Study Start: July 24, 2019
• Primary Completion: May 25, 2024
• Study Completion: May 25, 2024
• Last Updated: August 9, 2024

Record last verified: 2024-08

Locations

US (1)