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Combining CA-4948 with standard chemotherapy for advanced pancreatic cancer

A Phase I Clinical Trial of CA-4948 in Combination With Gemcitabine and Nab-Paclitaxel in Metastatic or Unresectable Pancreatic Ductal Carcinoma

Phase 1 Interventional National Cancer Institute (NCI) · NCT05685602

This study is testing if adding a new drug called CA-4948 to standard chemotherapy can help people with advanced pancreatic cancer feel better and improve their treatment results.

Quick facts

PhasePhase 1
Study typeInterventional
Enrollment36 (estimated)
Ages18 Years and up
SexAll
SponsorNational Cancer Institute (NCI) NIH
Drugs / interventionschemotherapy
Locations27 sites (Duarte, California and 26 other locations)
Trial IDNCT05685602 on ClinicalTrials.gov

What this trial studies

This phase I trial evaluates the safety and optimal dosage of emavusertib (CA-4948) when used alongside standard chemotherapy agents gemcitabine and nab-paclitaxel in patients with metastatic or unresectable pancreatic ductal adenocarcinoma. The study aims to assess dose-limiting toxicities, anti-tumor activity, and overall safety of the treatment combination. Patients will undergo various imaging techniques and tumor biopsies to monitor treatment response and collect data on pharmacodynamics and pharmacokinetics.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with confirmed metastatic or unresectable pancreatic ductal adenocarcinoma who have progressed after standard therapies.

Not a fit: Patients who have not progressed after prior gemcitabine or nab-paclitaxel treatment for metastatic disease may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve outcomes for patients with advanced pancreatic cancer who have limited options.

How similar studies have performed: While this approach is novel in combining CA-4948 with these specific chemotherapy agents, similar studies have shown promise in targeting cancer pathways with kinase inhibitors.

Eligibility criteria

Show full inclusion / exclusion 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)

Where this trial is running

Duarte, California and 26 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Metastatic Pancreatic Ductal AdenocarcinomaStage III Pancreatic Cancer AJCC v8Stage IV Pancreatic Cancer AJCC v8Unresectable Pancreatic Ductal Adenocarcinoma
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.