Status and phase
Conditions
Treatments
About
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:
Other interventions include
Full description
This is a two part Phase 1B study investigating whether NIS793 improves the clinical benefit of FOLFIRINOX treatment for metastatic pancreas adenocarcinoma.The first part is a safety run-in using a dose escalation strategy to determine the recommended phase 2 dose of the drug NIS793. In the second part participants will be a randomized assigned to receive either FOLFIRINOX plus NIS793 or FOLFIRINOX alone.
NIS793 binds to the protein that can be found on tumor cells, called TGFβ, thereby preventing its role in cancer metastasis (spreading). FOLFIRINOX is a combination of 4 chemotherapy drugs that may help shrink tumors.
The U.S. Food and Drug Administration (FDA) has not approved NIS793 as a treatment for any disease.
The FDA has approved FOLFIRINOX as a treatment option for metastatic pancreas adenocarcinoma The FDA has not approved the combination of NIS793 and FOLFIRINOX as a treatment for any disease.
The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits.
It is expected that about 50 people will take part in this research study.
Novartis, a pharmaceutical company, is supporting this research study by providing funding for the study, including the study drug.
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
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
Human immunodeficiency virus (HIV)-infected participants on effective antiretroviral therapy with undetectable viral load within 6 months are eligible for this trial.
For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
Participants with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression. Additionally, participants with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy.
Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, 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. To be eligible for study participation, participants must be class 2 B or better.
Exclusion criteria
Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed. COVID non-live vaccines are allowed.
Primary purpose
Allocation
Interventional model
Masking
4 participants in 3 patient groups
Loading...
Central trial contact
Colin D Weekes, MD, PhD; Joanna L Caufield, RN
Data sourced from clinicaltrials.gov
Clinical trials
Research sites
Resources
Legal