Trial Title:
CA-4948 Added to Standard Chemotherapy to Treat Metastatic or Unresectable Pancreatic Cancer
NCT ID:
NCT05685602
Condition:
Metastatic Pancreatic Ductal Adenocarcinoma
Stage III Pancreatic Cancer AJCC v8
Stage IV Pancreatic Cancer AJCC v8
Unresectable Pancreatic Ductal Adenocarcinoma
Conditions: Official terms:
Adenocarcinoma
Pancreatic Neoplasms
Paclitaxel
Albumin-Bound Paclitaxel
Gemcitabine
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Suspended
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Biopsy
Description:
Undergo a tumor biopsy
Arm group label:
Treatment (CA-4948, gemcitabine, nab-paclitaxel)
Other name:
BIOPSY_TYPE
Other name:
Bx
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo blood sample collection
Arm group label:
Treatment (CA-4948, gemcitabine, nab-paclitaxel)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo a CT scan
Arm group label:
Treatment (CA-4948, gemcitabine, nab-paclitaxel)
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography
Other name:
Computerized Axial Tomography
Other name:
Computerized axial tomography (procedure)
Other name:
Computerized Tomography
Other name:
Computerized Tomography (CT) scan
Other name:
CT
Other name:
CT Scan
Other name:
tomography
Intervention type:
Biological
Intervention name:
Emavusertib
Description:
Given PO
Arm group label:
Treatment (CA-4948, gemcitabine, nab-paclitaxel)
Other name:
AU 4948
Other name:
AU-4948
Other name:
CA 4948
Other name:
CA-4948
Other name:
CA4948
Other name:
Interleukin-1 Receptor-associated Kinase 4 Inhibitor CA-4948
Other name:
IRAK4 Inhibitor CA-4948
Intervention type:
Drug
Intervention name:
Gemcitabine Hydrochloride
Description:
Given IV
Arm group label:
Treatment (CA-4948, gemcitabine, nab-paclitaxel)
Other name:
dFdCyd
Other name:
Difluorodeoxycytidine Hydrochloride
Other name:
Gemcitabine HCI
Other name:
Gemzar
Other name:
LY 188011
Other name:
LY-188011
Other name:
LY188011
Intervention type:
Procedure
Intervention name:
Magnetic Resonance Imaging
Description:
Undergo MRI
Arm group label:
Treatment (CA-4948, gemcitabine, nab-paclitaxel)
Other name:
Magnetic Resonance
Other name:
Magnetic Resonance Imaging (MRI)
Other name:
Magnetic resonance imaging (procedure)
Other name:
Magnetic Resonance Imaging Scan
Other name:
Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
Other name:
MR
Other name:
MR Imaging
Other name:
MRI
Other name:
MRI Scan
Other name:
MRIs
Other name:
NMR Imaging
Other name:
NMRI
Other name:
Nuclear Magnetic Resonance Imaging
Other name:
sMRI
Other name:
Structural MRI
Intervention type:
Drug
Intervention name:
Nab-paclitaxel
Description:
Given IV
Arm group label:
Treatment (CA-4948, gemcitabine, nab-paclitaxel)
Other name:
ABI 007
Other name:
ABI-007
Other name:
ABI007
Other name:
Abraxane
Other name:
Albumin-bound Paclitaxel
Other name:
Albumin-Stabilized Nanoparticle Paclitaxel
Other name:
Nanoparticle Albumin-bound Paclitaxel
Other name:
Nanoparticle Paclitaxel
Other name:
Naveruclif
Other name:
Paclitaxel Albumin
Other name:
paclitaxel albumin-stabilized nanoparticle formulation
Other name:
Paclitaxel Nanoparticle Albumin-bound
Other name:
Paclitaxel Protein-Bound
Other name:
Protein-bound Paclitaxel
Intervention type:
Procedure
Intervention name:
Positron Emission Tomography
Description:
Undergo a PET scan
Arm group label:
Treatment (CA-4948, gemcitabine, nab-paclitaxel)
Other name:
Medical Imaging, Positron Emission Tomography
Other name:
PET
Other name:
PET Scan
Other name:
Positron emission tomography (procedure)
Other name:
Positron Emission Tomography Scan
Other name:
Positron-Emission Tomography
Other name:
proton magnetic resonance spectroscopic imaging
Other name:
PT
Intervention type:
Procedure
Intervention name:
X-Ray Imaging
Description:
Undergo an x-ray
Arm group label:
Treatment (CA-4948, gemcitabine, nab-paclitaxel)
Other name:
Conventional X-Ray
Other name:
Diagnostic Radiology
Other name:
Medical Imaging, X-Ray
Other name:
Plain film radiographs
Other name:
Radiographic Imaging
Other name:
Radiographic imaging procedure (procedure)
Other name:
Radiography
Other name:
RG
Other name:
Static X-Ray
Other name:
X-Ray
Summary:
This phase I trial tests the safety, side effects, and best dose of emavusertib (CA-4948)
in combination with gemcitabine and nab-paclitaxel in treating patients with pancreatic
ductal adenocarcinoma that has spread from where it first started (primary site) to other
places in the body (metastatic) or cannot be removed by surgery (unresectable). CA-4948
is in a class of medications called kinase inhibitors. It works by blocking the action of
abnormal proteins called interleukin-1 receptor-associated kinase 4 (IRAK4) and FMS-like
tyrosine kinase 3 (FLT3) that signal cells to multiply. This may help keep cancer cells
from growing. The usual approach for patients with pancreatic ductal adenocarcinoma is
treatment with chemotherapy drugs gemcitabine and nab-paclitaxel. Gemcitabine is a
chemotherapy drug that blocks the cells from making DNA and may kill cancer cells.
Paclitaxel is in a class of medications called anti-microtubule agents. It stops cancer
cells from growing and dividing and may kill them. Nab-paclitaxel is an
albumin-stabilized nanoparticle formulation of paclitaxel which may have fewer side
effects and work better than other forms of paclitaxel. Giving CA-4948 in combination
with gemcitabine and nab-paclitaxel may shrink or stabilize metastatic or unresectable
pancreatic ductal adenocarcinoma.
Detailed description:
PRIMARY OBJECTIVE:
I. To assess dose limiting toxicities and determine the recommended phase 2 dose of
emavusertib (CA--4948) in combination with chemotherapy in patients with pancreatic
ductal adenocarcinoma.
SECONDARY OBJECTIVES:
I. To observe and record anti-tumor activity. II. To evaluate the safety and tolerability
of the combination of CA-4948 and chemotherapy.
III. To determine preliminary signals of efficacy, as measured by objective response rate
(ORR), CA-4948 response, progression free survival (PFS), and overall survival (OS).
EXPLORATORY OBJECTIVES:
I. To evaluate pharmacodynamic effect of CA-4948 in combination with chemotherapy.
II. To evaluate pharmacokinetics of CA-4948 in combination with chemotherapy. III. To
explore biomarkers and genomic alterations associated with treatment response.
OUTLINE: This is a dose-escalation study of CA-4948 in combination with fixed-dose
gemcitabine and nab-paclitaxel followed by a dose-expansion study.
Patients receive CA-4948 orally (PO), gemcitabine intravenously (IV), and nab-paclitaxel
IV on study. Patients undergo magnetic resonance imaging (MRI), computed tomography (CT)
scan, positron emission tomography (PET) scan, and/or x-ray imaging throughout the trial.
Patients also undergo tumor biopsies and blood sample collection during screening and on
study.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Patients must have histologically or cytologically confirmed adenocarcinoma of the
pancreas that is metastatic or unresectable and for which standard curative or
palliative measures do not exist or are no longer effective
- Patients must have had disease progression on or after fluorouracil (5-FU)-based
therapy for metastatic or unresectable pancreatic ductal adenocarcinoma (PDAC). If
received gemcitabine-based regimen as adjuvant therapy, then gemcitabine and
nab-paclitaxel (if used) should be >12 months from study enrollment. Prior use of
gemcitabine/nab-paclitaxel for metastatic or unresectable disease is not allowed
- Age >= 18 years. Because no dosing or adverse event data are currently available on
the use of CA-4948 in combination with gemcitabine and nab-paclitaxel in patients <
18 years of age, children are excluded from this study
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
- Absolute neutrophil count >= 1,500/mcL
- Platelets >= 100,000/mcL
- Total bilirubin =< 1.5 x institutional upper limit of normal (ULN)
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase
[SGPT]) =< 3 x institutional ULN
- Glomerular filtration rate (GFR) >= 60 mL/min (based on the calculated Chronic
Kidney Disease Epidemiology Collaboration [CKD-EPI] glomerular filtration rate
estimation)
- Creatine phosphokinase (CPK) elevation at the screening < grade 2 (creatine
phosphokinase [CPK] =< 2.5 ULN)
- Patients on a cholesterol lowering statin must be on a stable dose with no dose
changes within 3 weeks prior to study start
- Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral
therapy with undetectable viral load within 6 months are eligible for this trial as
long as their anti-retroviral therapy does not have the potential for drug-drug
interactions as judged by the treating investigator
- For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV
viral load must be undetectable on suppressive therapy, if indicated
- Patients with a history of hepatitis C virus (HCV) infection must have been treated
and cured. For patients with HCV infection who are currently on treatment, they are
eligible if they have an undetectable HCV viral load
- Patients with treated brain metastases are eligible if follow-up brain imaging after
at least 4 weeks following central nervous system (CNS)-directed therapy shows no
evidence of progression
- Patients 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
- Patients 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, patients should be class 2B or better
- Patients must have lesions amenable to research biopsy for those enrolling to the
expansion cohort. The biopsy should be deemed feasible and safe for pre-biopsy
lesion assessment criteria
- The effects of CA-4948, nab-paclitaxel, and gemcitabine on the developing human
fetus are unknown. For this reason and because gemcitabine is known to be
teratogenic, embryotoxic, and fetotoxic in mice and rabbits, women of child-bearing
potential and men must agree to use adequate contraception (hormonal or barrier
method of birth control; abstinence) prior to study entry, for the duration of study
participation, and 6 months after completion of CA-4948, nab-paclitaxel, and
gemcitabine administration. Should a woman become pregnant or suspect she is
pregnant while she or her partner is participating in this study, she should inform
her treating physician immediately. Men treated or enrolled on this protocol must
also agree to use adequate contraception prior to the study, for the duration of
study participation, and 3 months after completion of CA-4948, nab-paclitaxel, and
gemcitabine administration
- Ability to understand and the willingness to sign a written informed consent
document. Participants with impaired decision-making capacity who have a
legally-authorized representative (LAR) and/or family member available will also be
eligible
Exclusion Criteria:
- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
nitrosoureas or mitomycin C) prior to entering the study
- Patients who have not recovered from clinically significant adverse events due to
prior anti-cancer therapy (i.e., have residual toxicities > grade 1) with the
exception of alopecia
- History of other malignancy with the exception of 1) malignancies for which all
treatment was completed at least 2 years before registration and the patient has no
evidence of disease; 2) or known indolent malignancies that do not require treatment
and will likely not alter the course of treatment of disease under treatment
- History of allogeneic organ or stem cell transplant
- Current use or anticipated need for alternative, holistic, naturopathic, or
botanical formulations used for the purpose of cancer treatment
- Patients who are receiving any other investigational agents
- History of allergic reactions attributed to compounds of similar chemical or
biologic composition to CA-4948 or other agents used in study
- Patients receiving any medications or substances that are inhibitors or inducers of
CYP3A4 are ineligible due to CA-4948 and nab-paclitaxel. Because the lists of these
agents are constantly changing, it is important to regularly consult a
frequently-updated medical reference. As part of the enrollment/informed consent
procedures, the patient will be counseled on the risk of interactions with other
agents, and what to do if new medications need to be prescribed or if the patient is
considering a new over-the-counter medicine or herbal product
- Patients with uncontrolled intercurrent illness
- Pregnant women are excluded from this study because gemcitabine is nucleoside
analogue with the potential for teratogenic or abortifacient effects. Because there
is an unknown but potential risk for adverse events in nursing infants secondary to
treatment of the mother with gemcitabine, breastfeeding should be discontinued if
the mother is treated with gemcitabine. These potential risks may also apply to
other agents used in this study
- Prolonged Fridericia's correction formula (QTcF) (> 470 in females, > 450 in males)
on screening electrocardiogram (ECG)
- Gastrointestinal condition which could impair absorption of CA-4948 or inability to
ingest CA-4948
- Severe obstructive pulmonary disease or interstitial lung disease
- History of rhabdomyolysis or elevated creatine phosphokinase (CPK)
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
City of Hope Comprehensive Cancer Center
Address:
City:
Duarte
Zip:
91010
Country:
United States
Facility:
Name:
UC Irvine Health/Chao Family Comprehensive Cancer Center
Address:
City:
Orange
Zip:
92868
Country:
United States
Facility:
Name:
UCHealth University of Colorado Hospital
Address:
City:
Aurora
Zip:
80045
Country:
United States
Facility:
Name:
Yale University Cancer Center LAO
Address:
City:
New Haven
Zip:
06520
Country:
United States
Facility:
Name:
Northwestern University
Address:
City:
Chicago
Zip:
60611
Country:
United States
Facility:
Name:
Memorial Hospital East
Address:
City:
Shiloh
Zip:
62269
Country:
United States
Facility:
Name:
University of Kentucky/Markey Cancer Center
Address:
City:
Lexington
Zip:
40536
Country:
United States
Facility:
Name:
Johns Hopkins University/Sidney Kimmel Cancer Center
Address:
City:
Baltimore
Zip:
21287
Country:
United States
Facility:
Name:
National Cancer Institute Developmental Therapeutics Clinic
Address:
City:
Bethesda
Zip:
20892
Country:
United States
Facility:
Name:
National Institutes of Health Clinical Center
Address:
City:
Bethesda
Zip:
20892
Country:
United States
Facility:
Name:
Siteman Cancer Center at West County Hospital
Address:
City:
Creve Coeur
Zip:
63141
Country:
United States
Facility:
Name:
Washington University School of Medicine
Address:
City:
Saint Louis
Zip:
63110
Country:
United States
Facility:
Name:
Siteman Cancer Center-South County
Address:
City:
Saint Louis
Zip:
63129
Country:
United States
Facility:
Name:
Siteman Cancer Center at Christian Hospital
Address:
City:
Saint Louis
Zip:
63136
Country:
United States
Facility:
Name:
Siteman Cancer Center at Saint Peters Hospital
Address:
City:
Saint Peters
Zip:
63376
Country:
United States
Facility:
Name:
NYU Langone Hospital - Long Island
Address:
City:
Mineola
Zip:
11501
Country:
United States
Facility:
Name:
Laura and Isaac Perlmutter Cancer Center at NYU Langone
Address:
City:
New York
Zip:
10016
Country:
United States
Facility:
Name:
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
Address:
City:
New York
Zip:
10032
Country:
United States
Facility:
Name:
UNC Lineberger Comprehensive Cancer Center
Address:
City:
Chapel Hill
Zip:
27599
Country:
United States
Facility:
Name:
University of Cincinnati Cancer Center-UC Medical Center
Address:
City:
Cincinnati
Zip:
45219
Country:
United States
Facility:
Name:
Ohio State University Comprehensive Cancer Center
Address:
City:
Columbus
Zip:
43210
Country:
United States
Facility:
Name:
University of Cincinnati Cancer Center-West Chester
Address:
City:
West Chester
Zip:
45069
Country:
United States
Facility:
Name:
University of Oklahoma Health Sciences Center
Address:
City:
Oklahoma City
Zip:
73104
Country:
United States
Facility:
Name:
University of Pittsburgh Cancer Institute (UPCI)
Address:
City:
Pittsburgh
Zip:
15232
Country:
United States
Facility:
Name:
University of Wisconsin Carbone Cancer Center - University Hospital
Address:
City:
Madison
Zip:
53792
Country:
United States
Start date:
June 12, 2023
Completion date:
March 15, 2025
Lead sponsor:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
National Cancer Institute (NCI)
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05685602
