A Trial of NIS793 With FOLFIRINOX in Pancreatic Cancer

NCT05546411 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 22-314
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 2

Brief Summary

This study is being done to evaluate the safety and efficacy of adding NIS793 to standard of care FOLFIRINOX treatment for pancreatic cancer. The names of the study interventions involved in this study are:

• NIS793
• FOLFIRINOX (Folinic acid/Leucovorin, 5-Fluorouracil, Irinotecan, and Oxaliplatin) Other interventions may include:
• Chemoradiation Therapy
• Surgery

Conditions

Pancreatic Cancer; Resectable Pancreatic Cancer; Borderline Resectable Pancreatic Adenocarcinoma; Pancreatic Adenocarcinoma

Keywords

Pancreatic Cancer; Resectable Pancreatic Cancer; Borderline Resectable Pancreatic Adenocarcinoma; Pancreatic Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Major Pathological Response Rate (MPR)

  Major pathological response (MPR) defined as \<5% residual tumor cells visible in the pancreatic resection specimen. The major pathological response rate will be analyzed among all patients who start protocol therapy, including those not resected due to early progression, death or off study.

  Pathology review is done in surgery assessments, once within 14 days prior to the operation.

Secondary Outcomes (3)

• Treatment-Related Toxicity Rate

  Cycle 1 Day 1 through 30 days post last treatment date, up to 9 months.

• Median Progression-free Survival (PFS)

  From randomization (or registration) to the earlier of progression or death due to any cause, up to 9 months. Participants alive without disease progression are censored at date of last disease evaluation.

• Median Overall Survival (OS)

  Post treatment follow up done at least once every 12 weeks (+/- 28 days), up to 9 months.

Study Arms (2)

mFOLFIRINOX + NIS793

EXPERIMENTAL

Participants will be randomly assigned to receive: * FOLFIRINOX + NIS793 on day 1 of each 14 day cycle up to 8 cycles/16 weeks * Cycles 9+: Based on study team determination, some participants may be offered chemoradiation following completion of chemotherapy and/or surgery following either completion of chemotherapy or chemoradiation

Drug: mFOLFIRINOX; Drug: 5-Fluorouracil (5-FU); Drug: Oxaliplatin; Drug: Irinotecan; Drug: Leucovorin; Drug: NIS793; Radiation: Chemoradiation; Procedure: Surgery

mFOLFIRINOX

ACTIVE COMPARATOR

Participants will be randomly assigned to receive: * FOLFIRINOX on day 1 of each 14 day cycle up to 8 cycles/16 weeks * Cycles 9+: Based on study team determination, some participants may be offered chemoradiation following completion of chemotherapy and/or surgery following either completion of chemotherapy or chemoradiation

Drug: mFOLFIRINOX; Drug: 5-Fluorouracil (5-FU); Drug: Oxaliplatin; Drug: Irinotecan; Drug: Leucovorin; Radiation: Chemoradiation; Procedure: Surgery

Interventions

mFOLFIRINOX DRUG

Combination of the drugs 5-Fluorouracil (5-FU), Oxaliplatin, Irinotecan, and Leucovorin given by intravenous infusion

mFOLFIRINOX; mFOLFIRINOX + NIS793

5-Fluorouracil (5-FU) DRUG

Part of the FOLFIRINOX drug combination, given by intravenous infusion

Also known as: Adrucil

mFOLFIRINOX; mFOLFIRINOX + NIS793

Oxaliplatin DRUG

Part of the FOLFIRINOX drug combination, given by intravenous infusion

Also known as: Eloxatin

mFOLFIRINOX; mFOLFIRINOX + NIS793

Irinotecan DRUG

Part of the FOLFIRINOX drug combination, given by intravenous infusion

Also known as: Camptosar, Camptothecin-11, CPT-1

mFOLFIRINOX; mFOLFIRINOX + NIS793

Leucovorin DRUG

Part of the FOLFIRINOX drug combination, given by intravenous infusion

Also known as: Calcium Leucovorin, Citrovorum Factor, Folinic Acid

mFOLFIRINOX; mFOLFIRINOX + NIS793

NIS793 DRUG

Given by intravenous infusion

mFOLFIRINOX + NIS793

Chemoradiation RADIATION

Combination of Chemo (Capecitabine) and Radiation Therapy

mFOLFIRINOX; mFOLFIRINOX + NIS793

Surgery PROCEDURE

Surgical removal of tumor

mFOLFIRINOX; mFOLFIRINOX + NIS793

Eligibility Criteria

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

You may qualify if:

• The clinical, radiographic, and pathologic evidence support a diagnosis of pancreatic adenocarcinoma, with histology confirmatory for adenocarcinoma.
• Subjects must be determined to meet the criteria for resectable or borderline resectable pancreatic cancer based on the M.D. Anderson Cancer Center (MDACC) and Alliance Intergroup Criteria classification at initial diagnosis (Table 1). Patients with locally advanced or metastatic disease are not eligible for this trial.
• Criteria for resectability of pancreatic cancer
• Vessel: SMA, Resectable: No extension; normal fat plane between the tumor and the artery, Borderline resectable: Interface between tumor and vessel measuring less than 180º of the circumference of the vessel wall, Locally advanced (Not Eligible): Encased (\>180°)
• Vessel: Celiac axis, Resectable: No extension, Borderline resectable: Interface between tumor and vessel measuring less than 180º of the circumference of the vessel wall, Locally advanced (Not Eligible): Encased and no technical option for reconstruction usually because of extension to the celiac axis/ splenic/left gastric junction or the celiac origin
• Vessel: Common hepatic artery, Resectable: No extension, Borderline resectable: Reconstructable§, short-segment interface between tumor and vessel of any degree, Locally advanced (Not Eligible): Encased and no technical option for reconstruction usually because of extension to the celiac axis/ splenic/left gastric junction or the celiac origin Vessel: SMV/PV, Resectable: Patent, Borderline resectable:SMV/PV Patent Interface between tumor and vessel measuring 180º or greater of the circumference of the vessel wall, and/or reconstructable§ occlusion Occluded and no technical option for reconstruction, Locally advanced (Not Eligible): Occluded and no technical option for reconstruction
• Referenced from: Varadhachary et al., 2006(6) and Katz et al, 2013 (8). SMA, superior mesenteric artery; SMV/PV, superior mesenteric vein/portal vein.
• Normal vein or artery proximal and distal to the site of suggested tumor-vessel involvement suitable for vascular reconstruction
• In subjects requiring biliary decompression, biliary stent or drainage using percutaneous transhepatic cholangiogram (PTC) are allowed.
• Participants must be ≥18 years of age at the time of enrollment.
• Participants must have an ECOG performance status 0-1 (see Appendix A).
• Participants must have adequate organ and marrow function as defined as:
• Absolute neutrophil count ≥1,500/mcL
• Platelets ≥100,000/mcL
• Total bilirubin ≤1.5 × institutional upper limit of normal

You may not qualify if:

• Has locally advanced or metastatic disease as determined by CT scan or MRI.
• Tumors with histologic features in addition to an adenocarcinoma component are excluded. Variant histologies include but are not limited to adenosquamous, squamous, neuroendocrine, undifferentiated with osteoclast like giant cells, acinar, hepatoid, medullary carcinomas.
• Has either had any prior chemotherapy or targeted small molecule therapy, or immunotherapy or radiation therapy for pancreatic cancer.
• Note: If subject received major surgery for reason other than pancreatic cancer they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Has a known prior or current synchronous malignancy, except:
• Malignancy that was treated with curative intent and for which there has been no known active disease for \>5 years prior to enrollment
• Curatively treated non-melanoma skin cancer, cervical cancer in situ or prostatic intraepithelial neoplasia, without evidence of prostate cancer.
• Significant history of uncontrolled cardiac disease defined as uncontrolled hypertension (defined by a systolic BP \>=160 mm Hg and/or diastolic BP \>= 100mm Hg), unstable angina, myocardial infarction within the last 4 months, or uncontrolled congestive heart failure. Subjects with a history of cardiac disease should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants should be class 2B or better.
• Has a medical history or current diagnosis of myocarditis.
• Has a left ventricular ejection fraction \<50%, cardiac valvulopathy \> grade 2, or elevated cardiac enzymes (troponin I) elevation \> 2x ULN.
• Has a condition/s that are considered to have a high risk of clinically significant GI bleed or any other condition associated with or history of significant bleeding.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Patients receiving physiological replacement doses of corticosteroids (10mg of prednisone or equivalent) are allowed.
• Has known active, uncontrolled HIV (high viral load), Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA \[qualitative\] is detected).
• Patients who have been vaccinated for hepatitis B and do not have a history of infection are eligible.
• Has received a live vaccine within 30 days prior to the first dose of trial treatment. COVID-19 vaccination or booster is permitted any time prior to enrollment or during treatment on trial, in a manner consistent with individual institutional guidelines.

Sponsors & Collaborators

• Kimberly Perez, MD: lead
• Novartis: collaborator

Study Sites (2)

Brigham and Women's Hospital

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Fluorouracil; Oxaliplatin; Irinotecan; Leucovorin; NIS-793; Chemoradiotherapy; 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)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Coordination Complexes; Organic Chemicals; Camptothecin; Alkaloids; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Combined Modality Therapy; Therapeutics; Drug Therapy; Radiotherapy

Results Point of Contact

• Title: Kimberly Perez, MD
• Organization: Dana Farber Cancer Institute

KIMBERLY_PEREZ@DFCI.HARVARD.EDU

617-632-5370

Study Officials

• Kimberly Perez, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: September 7, 2022
• First Posted: September 19, 2022
• Study Start: January 6, 2023
• Primary Completion: August 16, 2023
• Study Completion: October 13, 2023
• Last Updated: December 17, 2024
• Results First Posted: July 16, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (2)