FOLFIRINOX + NIS793 in Pancreatic Cancer

NCT05417386 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: 22-082
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

This research is being done to evaluate the safety and effectiveness of the drug NIS793 in combination with the standard of care treatment FOLFIRINOX (consists of the drugs 5-Fluorouracil (5-FU), Oxaliplatin, Irinotecan, and Leucovorin), chemoradiation and surgery for people with metastatic pancreas adenocarcinoma. The drugs involved in this study are:

• NIS793
• FOLFIRINOX (consists of the drugs 5-Fluorouracil (5-FU), Oxaliplatin, Irinotecan, and Leucovorin) Other interventions include
• chemoradiation
• surgery.

Conditions

Pancreas Cancer; Metastatic Pancreatic Cancer; Metastatic Pancreatic Adenocarcinoma

Keywords

Pancreas Cancer; Metastatic Pancreatic Cancer; Metastatic Pancreatic Adenocarcinoma

Outcome Measures

Primary Outcomes (2)

• Safety Run In-Recommended Phase 2 dose (RP2D)

  Primary endpoint of safety run-in cohort is to define the recommended phase 2 dose as analyzed by 2-dimensional imaging (Computed Tomography, CT) or MRI utilizing Response Evaluation Criteria in Solid Tumors (RECIST v.1.1), obtained at 4-cycle therapy intervals.

  Up to 2 months after baseline

• R0 Resection Rate

  The primary endpoint of the two-arm non-comparative phase IB study (Part 2) is to estimate the R0 resection rate associated with the FOLFIRINOX/NIS793 therapy administered as neoadjuvant therapy.

  Up to 8 months after baseline

Secondary Outcomes (5)

• Disease-Free Survival (DFS)

  Up to approximately 6 years after baseline

• Progression-free survival (PFS)

  Up to approximately 6 years after baseline

• Overall survival (OS)

  Up to approximately 6 years after baseline

• Pathologic complete response (pCR)

  up to 8 months after baseline

• Resection rate

  up to 8 months after baseline

Study Arms (3)

Safety Run-In

EXPERIMENTAL

Following a 3 + 3 dose escalation design 6-18 participants will receive NIS793 and FOLFIRINOX on day 1 of each 14 day cycle for 3+ cycles until recommended phase 2 dose is determined.

Drug: FOLFIRINOX; Drug: NIS793

FOLFIRINOX

EXPERIMENTAL

Participants will be randomly assigned to receive: * FOLFIRINOX on day 1 of each 14 day cycle for cycles 1-8 * Cycles 9+: Chemoradiation (CRT) and surgery

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

FOLFIRINOX + NIS793

EXPERIMENTAL

Participants will be randomly assigned to receive: * FOLFIRINOX FOLFIRINOX + NIS793 on day 1 of each 14 day cycle for cycles 1-8 * Cycles 9+: Chemoradiation (CRT) with NIS793, Surgery, NIS793

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

Interventions

FOLFIRINOX DRUG

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

Also known as: 5FU, leucovorin, irinotecan, oxaliplatin

FOLFIRINOX; FOLFIRINOX + NIS793; Safety Run-In

Oxaliplatin DRUG

Part of the FOLFIRINOX drug combination, given by intravenous infusion

Also known as: Eloxatin

FOLFIRINOX; FOLFIRINOX + NIS793

Leucovorin DRUG

Part of the FOLFIRINOX drug combination, given by intravenous infusion

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

FOLFIRINOX; FOLFIRINOX + NIS793

Irinotecan DRUG

Part of the FOLFIRINOX drug combination, given by intravenous infusion

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

FOLFIRINOX; FOLFIRINOX + NIS793

5-Fluorouracil (5-FU) DRUG

Part of the FOLFIRINOX drug combination, given by intravenous infusion

Also known as: Adrucil

FOLFIRINOX; FOLFIRINOX + NIS793

NIS793 DRUG

Given by intravenous infusion

Also known as: Nisevokitug

FOLFIRINOX + NIS793; Safety Run-In

Chemoradiation RADIATION

Combination of Chemo (Capecitabine) and Radiation Therapy

FOLFIRINOX; FOLFIRINOX + NIS793

Capecitabine DRUG

Taken Orally as part of Chemoradiation

Also known as: Xeloda

FOLFIRINOX; FOLFIRINOX + NIS793

Radiation Therapy RADIATION

Radiation Therapy as part of Chemoradiation

FOLFIRINOX; FOLFIRINOX + NIS793

Surgery PROCEDURE

Surgical removal of tumor

FOLFIRINOX; FOLFIRINOX + NIS793

Eligibility Criteria

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

You may qualify if:

• Safety Run-in Cohort: Histologically confirmed metastatic pancreatic adenocarcinoma without prior therapy for pancreatic adenocarcinoma.
• Phase 1B Cohort: Histologically confirmed locally advanced disease (borderline resectable or locally advanced pancreatic adenocarcinoma) or poorly differentiated adenosquamous carcinoma includes both borderline resectable or locally advanced disease. Patients with localized pancreas adenocarcinoma cannot have received any prior therapy for borderline resectable or locally advanced pancreas adenocarcinoma
• Borderline Resectable Disease: 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.
• Locally Advanced Pancreas Adenocarcinoma: 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. Participants must have measurable disease, defined as at least one lesion that measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥20 mm (≥2 cm) by chest x-ray or as ≥10 mm (≥1 cm) with CT scan, MRI, or calipers by clinical exam. See Section 12 (Measurement of Effect) for the evaluation of measurable disease.
• Age ≥18 years.
• ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A).
• Participants must have adequate organ and marrow function as defined below:
• Absolute neutrophil count ≥1,500/mcL
• Platelets ≥100,000/mcL
• Total bilirubin ≤ 1.5 institutional upper limit of normal (ULN) if no biliary stenting has been done OR 2.0 x ULN if patient is status post biliary stenting or two downward trending values.
• AST(SGOT)/ALT(SGPT) Safety Run-in Metastatic Disease: \< 5 x institutional ULN. Locally advanced disease: ≤3 × institutional ULN
• Creatinine ≤ institutional ULN OR
• Glomerular filtration rate (GFR) no lower than 60 mL/min/1.73 m2
• Creatinine clearance for males = (140 - age \[yrs\]) (body wt \[kg\]) / (72) (serum creatinine \[mg/dL\])
• Creatinine clearance for females = 0.85 x male value

You may not qualify if:

• Metastatic Disease Safety Run-in: Any prior chemotherapy, radiation therapy, immunotherapy, biologic ('targeted') therapy or investigational therapy for pancreas adenocarcinoma.
• Locally Advanced Disease Cohort: Any prior chemotherapy, radiation therapy, immunotherapy, biologic ('targeted') therapy or investigational therapy for treatment of the patient's pancreatic tumor.
• Major surgery, excluding laparoscopy, within 4 weeks of the start of study treatment, without complete recovery
• Patients with deficient mismatch/microsatellite unstable or high tumor mutation burden cancers.
• Participation in any investigational drug study within 4 weeks preceding the start of study treatment.
• Participants who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> Grade 1) with the exception of alopecia.
• Patients requiring use of steroids to treat active uncontrolled brain metastases will be excluded from study enrollment. Patients treated with radiation \> 4 weeks prior with follow up imaging showing control are eligible.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to NIS793, 5-fluorouracil, irinotecan and oxaliplatin not amenable to institutional chemotherapy desensitization protocol.
• Known, existing uncontrolled coagulopathy. Concomitant treatment with full dose warfarin (coumadin) is NOT allowed. Patients may receive low molecular weight heparin (LMWH) (such as enoxaparin and dalteparin) and direct oral anticoagulant (DOAC) for management of deep venous thrombosis (DVT).
• History of bleeding diathesis or recent major bleeding events (i.e. Grade \> 2 bleeding events in the month prior to treatment).
• Concomitant use of cimetidine, as it can decrease clearance of 5FU. Another H2- blocker or proton pump inhibitor may be substituted before study entry.
• Patient with cardiac ventricular arrhythmias requiring antiarrhythmic therapy, or atrioventricular heart block (due to 5FU administration)
• Participants with uncontrolled intercurrent illness or infection.
• Participants with uncontrolled seizures, central nervous system disorders or psychiatric illness/social situations that would limit compliance with study requirements.
• Has received a live vaccine within 30 days of planned start of study therapy. Note:

Sponsors & Collaborators

• Colin D. Weekes, M.D., PhD: lead
• Novartis: collaborator

Study Sites (1)

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

folfirinox; Fluorouracil; Leucovorin; Irinotecan; Oxaliplatin; NIS-793; Chemoradiotherapy; Capecitabine; Radiotherapy; 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; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Camptothecin; Alkaloids; Coordination Complexes; Organic Chemicals; Combined Modality Therapy; Therapeutics; Drug Therapy; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Colin D Weekes, MD, PHD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• 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: June 7, 2022
• First Posted: June 14, 2022
• Study Start: August 9, 2022
• Primary Completion: July 10, 2023
• Study Completion: July 10, 2023
• Last Updated: November 18, 2025

Record last verified: 2025-11

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 Partners Innovations team at http://www.partners.org/innovation

Locations

US (1)