CA-4948 Added to Standard Chemotherapy to Treat Metastatic or Unresectable Pancreatic Cancer
A Phase I Clinical Trial of CA-4948 in Combination With Gemcitabine and Nab-Paclitaxel in Metastatic or Unresectable Pancreatic Ductal Carcinoma
4 other identifiers
interventional
43
1 country
26
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Jun 2023
Longer than P75 for phase_1
26 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 13, 2023
CompletedFirst Posted
Study publicly available on registry
January 17, 2023
CompletedStudy Start
First participant enrolled
June 12, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 30, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
April 30, 2027
April 29, 2026
April 1, 2026
3.9 years
January 13, 2023
April 28, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Dose limiting toxicity rate
Done to determine the maximum tolerated dose for the combination of CA-4948 and gemcitabine/nab-paclitaxel chemotherapy backbone. Data analysis of the study will be descriptive in nature. Demographic and clinical characteristics of the sample, toxicity by severity, as well as loss to follow-up will be summarized using descriptive statistics. Safety endpoints will be listed for each dose level.
Up to 1 year
Secondary Outcomes (4)
Incidence of adverse events
Up to 1 year
Overall response rate (ORR)
Up to 1 year
Progression-free survival (PFS)
From start of study treatment to time of progression or death, whichever occurs first, assessed up to 1 year
Overall survival (OS)
Up to 1 year
Other Outcomes (2)
Pharmacodynamic effect of CA-4948 in combination with chemotherapy
Up to 1 year
Pharmacokinetics (PK) of both CA-4948 and nab-paclitaxel
Cycle 1 day 1 (C1D1) (pre-dose, 0.5, 1, 2, 4, 6, 8 hours [h]), C1D8 (pre-dose), C2D1 (pre-dose, 0.5, 1, 2, 4, 6, 8h), C2D2: (24h post C2D1 dose), C2D8 (pre-dose), C3D1 (pre-dose), C3D17 (+/- 3 d)
Study Arms (1)
Treatment (CA-4948, gemcitabine, nab-paclitaxel)
EXPERIMENTALPatients receive CA-4948 PO BID on days 1-21 or 1-28 of each cycle, gemcitabine IV over 30-60 minutes on days 1 and 8 or 1, 8, and 15 of each cycle, and nab-paclitaxel IV over 30-40 minutes on days 1 and 8 or 1, 8, and 15 of each cycle. Cycles repeat every 21 or 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, tumor biopsies, and blood sample collection throughout the trial.
Interventions
Undergo a CT scan
Given PO
Undergo tumor biopsies
Undergo blood sample collection
Given IV
Given IV
Eligibility Criteria
You may qualify if:
- 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
- +6 more criteria
You may not qualify if:
- 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 neuropathy, which should resolve to grade 2, or 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)
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (26)
City of Hope Comprehensive Cancer Center
Duarte, California, 91010, United States
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
Irvine, California, 92612, United States
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, 92868, United States
UCHealth University of Colorado Hospital
Aurora, Colorado, 80045, United States
Northwestern University
Chicago, Illinois, 60611, United States
Memorial Hospital East
Shiloh, Illinois, 62269, United States
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287, United States
National Cancer Institute Developmental Therapeutics Clinic
Bethesda, Maryland, 20892, United States
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892, United States
Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri, 63376, United States
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, 63141, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Siteman Cancer Center-South County
St Louis, Missouri, 63129, United States
Siteman Cancer Center at Christian Hospital
St Louis, Missouri, 63136, United States
NYU Langone Hospital - Long Island
Mineola, New York, 11501, United States
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, 10016, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, 10032, United States
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599, United States
University of Cincinnati Cancer Center-UC Medical Center
Cincinnati, Ohio, 45219, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
University of Cincinnati Cancer Center-West Chester
West Chester, Ohio, 45069, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232, United States
University of Wisconsin Carbone Cancer Center - Eastpark Medical Center
Madison, Wisconsin, 53718, United States
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, 53792, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Patrick Grierson
Yale University Cancer Center LAO
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 13, 2023
First Posted
January 17, 2023
Study Start
June 12, 2023
Primary Completion (Estimated)
April 30, 2027
Study Completion (Estimated)
April 30, 2027
Last Updated
April 29, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
"NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page."