CA-4948 + Chemotherapy for Pancreatic Cancer
Recruiting in Palo Alto (17 mi)
+29 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: National Cancer Institute (NCI)
Must not be taking: CYP3A4 inhibitors/inducers
Disqualifiers: Chemotherapy, Radiotherapy, Transplant, others
No Placebo Group
Trial Summary
What is the purpose of this trial?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.
Do I need to stop my current medications to join the trial?
The trial does not specify if you need to stop all current medications, but you cannot take medications that affect CYP3A4 enzymes. You should discuss your current medications with the trial team to ensure there are no interactions.
What data supports the effectiveness of the drug Emavusertib (CA-4948) for pancreatic cancer?
Research shows that combining gemcitabine with other drugs like bevacizumab and erlotinib has been effective in treating advanced pancreatic cancer, suggesting that combining Emavusertib with chemotherapy might also be beneficial.
12345What makes the drug Emavusertib (CA-4948) unique for treating pancreatic cancer?
Emavusertib (CA-4948) is unique because it is a novel drug that targets specific pathways in cancer cells, potentially offering a new mechanism of action compared to standard treatments like gemcitabine and 5-fluorouracil, which are commonly used for pancreatic cancer.
16789Eligibility Criteria
Adults with pancreatic ductal adenocarcinoma that's spread or can't be surgically removed, who've had disease progression after fluorouracil-based therapy. Must have proper kidney function, no recent statin dose changes, controlled HIV or hepatitis C if present, and agree to contraception. Excludes pregnant women, those with certain heart diseases or other cancers that could affect the trial outcome.Inclusion Criteria
My brain scans show no cancer growth after treatment for brain metastases.
I have been on the same dose of cholesterol medication for at least 3 weeks.
My kidney function, measured by GFR, is 60 mL/min or higher.
+17 more
Exclusion Criteria
I am not taking drugs that affect CYP3A4 due to my treatment.
You have had allergic reactions to drugs similar to CA-4948 or other drugs used in the study.
I am using or plan to use natural remedies for my cancer.
+11 more
Participant Groups
The safety and optimal dosage of emavusertib (CA-4948) combined with standard chemotherapy drugs gemcitabine and nab-paclitaxel are being tested. This study aims to see if adding CA-4948—a kinase inhibitor targeting specific cancer cell proteins—to usual chemotherapy can better control metastatic or unresectable pancreatic cancer.
1Treatment groups
Experimental Treatment
Group I: Treatment (CA-4948, gemcitabine, nab-paclitaxel)Experimental Treatment9 Interventions
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.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Siteman Cancer Center at Saint Peters HospitalSaint Peters, MO
Northwestern UniversityChicago, IL
National Cancer Institute Developmental Therapeutics ClinicBethesda, MD
University of Oklahoma Health Sciences CenterOklahoma City, OK
More Trial Locations
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Who Is Running the Clinical Trial?
National Cancer Institute (NCI)Lead Sponsor
References
Matuzumab short-term therapy in experimental pancreatic cancer: prolonged antitumor activity in combination with gemcitabine. [2022]The epidermal growth factor receptor ErbB-1 is commonly expressed in pancreatic cancer and ErbB-1 targeting has shown promising results. We wanted to evaluate matuzumab (EMD72000), a fully humanized ErbB-1-specific monoclonal antibody in combination with gemcitabine in experimental pancreatic cancer.
Docetaxel plus gemcitabine in combination with capecitabine as treatment for inoperable pancreatic cancer: a phase II study. [2022]To evaluate the activity and tolerance of gemcitabine in combination with docetaxel and capecitabine in previously untreated patients with advanced pancreatic cancer.
Gemcitabine plus bevacizumab compared with gemcitabine plus placebo in patients with advanced pancreatic cancer: phase III trial of the Cancer and Leukemia Group B (CALGB 80303). [2022]The combination of gemcitabine plus bevacizumab produced a 21% response rate and a median survival of 8.8 months in a multicenter phase II trial in patients with metastatic pancreatic cancer. These encouraging data led Cancer and Leukemia Group B (CALGB) to conduct a double-blind, placebo-controlled, randomized phase III trial of gemcitabine/bevacizumab versus gemcitabine/placebo in advanced pancreatic cancer patients.
The combination of a chemotherapy doublet (gemcitabine and capecitabine) with a biological doublet (bevacizumab and erlotinib) in patients with advanced pancreatic adenocarcinoma. The results of a phase I/II study. [2022]Preclinical data support the combined inhibition of vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) pathways in the treatment of pancreatic cancer. Following a dose finding phase I study the efficacy and toxicity of a four-drug regimen utilising the cytotoxic doublet of gemcitabine and capecitabine (GemCap), with the biological doublet of erlotinib and bevacizumab were further assessed in patients with advanced pancreatic cancer.
Treatment of metastatic pancreatic cancer. [2022]Pancreatic adenocarcinoma represents the fourth-leading cause of cancer-related mortality in the United States. The vast majority of patients are diagnosed at advanced stages of the disease when surgery is no longer an option. For these patients, systemic therapy remains the mainstay of care. Although single-agent gemcitabine has remained the standard of care since its approval in 1997, improvements in patient outcomes may potentially be realized by (1) applying pharmacokinetic principles to optimize drug delivery, such as the administration of gemcitabine at a "fixed-dose rate" infusion; (2) combining gemcitabine with other cytotoxic agents for which evidence of synergy exists, such as platinum compounds; and (3) integrating novel targeted agents such as bevacizumab, erlotinib, and cetuximab into treatment paradigms, based on an increasing understanding of the molecular pathways that govern pancreatic tumor growth and maintenance. This article provides the evidence to support each of these approaches and highlights future directions in the management of metastatic pancreatic cancer.
Gemcitabine and Infusional 5-Fluorouracil in Advanced Pancreatic Cancer: A Clinical Benefit Response-Oriented Phase II Study. [2015]Gemcitabine and 5-fluorouracil (5-FU) are two compounds with reproducible activity against advanced pancreatic carcinomas. To evaluate the activity and feasibility of this combination chemotherapy, a multi-institutional phase II study was performed.
Comparative pharmacokinetics and metabolic pathway of gemcitabine during intravenous and intra-arterial delivery in unresectable pancreatic cancer patients. [2022]To study the pharmacokinetics and clinical outcome of gemcitabine (2'-2'-difluoro-deoxcytidine [dFdC]) during intra-arterial versus intravenous delivery in locally advanced and regionally metastatic pancreatic cancer.
[The mechanism of resistance to 2', 2'-difluorodeoxycytidine (gemcitabine) in a pancreatic cancer cell line]. [2022]To study the mechanism of resistance and its reversal to 2', 2'-difluorodeoxycytidine (gemcitabine) in a pancreatic cancer cell line SW1990.
Pancreatic cancer: are we moving forward yet? Highlights from the Gastrointestinal Cancers Symposium. Orlando, FL, USA. January 20th, 2007. [2018]Survival for patients with pancreatic cancer remains abysmal. Standard treatment for resected and locally advanced disease usually consists of 5-fluorouracil (5-FU, either bolus or continuous infusion) and external beam radiation. However, recent studies have shown the role of gemcitabine either used alone or incorporated with 5-FU and external beam radiation in this setting. Gemcitabine and erlotinib (Tarceva) are currently the only standard chemotherapeutic agents approved by FDA for the treatment of advanced pancreatic cancer. Combination chemotherapy trials incorporating gemcitabine with other agents such as 5-FU, oxaliplatin, or capecitabine generally show improved outcomes in objective response rates but with little or no improvement in survival in phase III trials. In this article, the author summarizes the key studies in pancreatic cancer presented at the 2007 Gastrointestinal Cancers Symposium (Orlando, FL, USA; January, 2007). The studies discussed here include preliminary results of the Cancer and Leukemia Group B (CALGB) phase III trial of gemcitabine plus bevacizumab and activity of other targeted agents including sorafenib, cetuximab, retrospective and population-based studies evaluating the role of chemo-radiotherapy and radiotherapy, an analysis of 3,306 patients from the Surveillance, Epidemiology and End Results (SEER) database evaluating the predictive role of lymph nodes in survival following pancreatectomy and the assessment of novel agents, such as Genexol-PM and S-1.