Stage IV Pancreatic Cancer AJCC v8 Clinical Trial
Official title:
A Phase I Clinical Trial of CA-4948 in Combination With Gemcitabine and Nab-Paclitaxel in Metastatic or Unresectable Pancreatic Ductal Carcinoma
Verified date | June 2024 |
Source | National Cancer Institute (NCI) |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Suspended |
Enrollment | 36 |
Est. completion date | March 15, 2025 |
Est. primary completion date | March 15, 2025 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | 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) |
Country | Name | City | State |
---|---|---|---|
United States | UCHealth University of Colorado Hospital | Aurora | Colorado |
United States | Johns Hopkins University/Sidney Kimmel Cancer Center | Baltimore | Maryland |
United States | National Cancer Institute Developmental Therapeutics Clinic | Bethesda | Maryland |
United States | National Institutes of Health Clinical Center | Bethesda | Maryland |
United States | UNC Lineberger Comprehensive Cancer Center | Chapel Hill | North Carolina |
United States | Northwestern University | Chicago | Illinois |
United States | University of Cincinnati Cancer Center-UC Medical Center | Cincinnati | Ohio |
United States | Ohio State University Comprehensive Cancer Center | Columbus | Ohio |
United States | Siteman Cancer Center at West County Hospital | Creve Coeur | Missouri |
United States | City of Hope Comprehensive Cancer Center | Duarte | California |
United States | University of Kentucky/Markey Cancer Center | Lexington | Kentucky |
United States | University of Wisconsin Carbone Cancer Center - University Hospital | Madison | Wisconsin |
United States | NYU Langone Hospital - Long Island | Mineola | New York |
United States | Yale University Cancer Center LAO | New Haven | Connecticut |
United States | Laura and Isaac Perlmutter Cancer Center at NYU Langone | New York | New York |
United States | NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center | New York | New York |
United States | University of Oklahoma Health Sciences Center | Oklahoma City | Oklahoma |
United States | UC Irvine Health/Chao Family Comprehensive Cancer Center | Orange | California |
United States | University of Pittsburgh Cancer Institute (UPCI) | Pittsburgh | Pennsylvania |
United States | Siteman Cancer Center at Christian Hospital | Saint Louis | Missouri |
United States | Siteman Cancer Center-South County | Saint Louis | Missouri |
United States | Washington University School of Medicine | Saint Louis | Missouri |
United States | Siteman Cancer Center at Saint Peters Hospital | Saint Peters | Missouri |
United States | Memorial Hospital East | Shiloh | Illinois |
United States | University of Cincinnati Cancer Center-West Chester | West Chester | Ohio |
Lead Sponsor | Collaborator |
---|---|
National Cancer Institute (NCI) |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | Pharmacodynamic effect of CA-4948 in combination with chemotherapy | Pharmacodynamic indices from biopsies obtained from expansion cohorts will be summarized using descriptive statistics (means, median, and standard deviations) at each measurement time point and the change will be compared by paired t-test or Wilcoxon rank-sum test as appropriate. | Up to 1 year | |
Other | Pharmacokinetics (PK) of both CA-4948 and nab-paclitaxel | Done to confirm whether a clinically relevant drug-drug interaction occurs. Plasma concentration-time curves will be analyzed by noncompartmental methods using routines supplied in the Phoenix WinNonlin Professional software package. Exposure obtained by noncompartmental methods will also be compared to toxicity and efficacy outcomes using graphical and statistical programs. A formal population PK or exposure-response analyses may be conducted based on these initial findings. | Up to 1 year | |
Primary | 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 | Incidence of adverse events | Tabulations of adverse events will be produced by severity and by relationship to study drug. | Up to 1 year | |
Secondary | Overall response rate (ORR) | For efficacy data in the expansion cohort, ORR and its 95% confidence interval will be calculated. | Up to 1 year | |
Secondary | Progression-free survival (PFS) | Will be described using Kaplan-Meier product limit methods. | From start of study treatment to time of progression or death, whichever occurs first, assessed up to 1 year | |
Secondary | Overall survival (OS) | Will be described using Kaplan-Meier product limit methods. | Up to 1 year |
Status | Clinical Trial | Phase | |
---|---|---|---|
Withdrawn |
NCT03925428 -
Testing a New Anti-cancer Drug Combination, Entinostat and GSK525762C, for Advanced and Refractory Solid Tumors and Lymphomas
|
Phase 1 | |
Active, not recruiting |
NCT04524702 -
Paricalcitol and Hydroxychloroquine in Combination With Gemcitabine and Nab-Paclitaxel for Advanced Pancreatic Cancer
|
Phase 2 | |
Recruiting |
NCT04158635 -
Gemcitabine, Nab-Paclitaxel, and Bosentan for the Treatment of Unresectable Pancreatic Cancer
|
Phase 1 | |
Recruiting |
NCT04132505 -
Binimetinib and Hydroxychloroquine in Treating Patients With KRAS Mutant Metastatic Pancreatic Cancer
|
Phase 1 | |
Active, not recruiting |
NCT04514497 -
Testing the Addition of an Anti-cancer Drug, BAY 1895344, to Usual Chemotherapy for Advanced Stage Solid Tumors, With a Specific Focus on Patients With Small Cell Lung Cancer, Poorly Differentiated Neuroendocrine Cancer, and Pancreatic Cancer
|
Phase 1 | |
Recruiting |
NCT04673448 -
Niraparib and TSR-042 for the Treatment of BRCA-Mutated Unresectable or Metastatic Breast, Pancreas, Ovary, Fallopian Tube, or Primary Peritoneal Cancer
|
Phase 1 | |
Not yet recruiting |
NCT06206876 -
FL118 for Treating Patients With Advanced Pancreatic Ductal Adenocarcinoma
|
Phase 1 | |
Recruiting |
NCT05053971 -
Testing A New Anti-cancer Drug Combination, Entinostat and ZEN003694, for Advanced and Refractory Solid Tumors and Lymphomas
|
Phase 1/Phase 2 | |
Terminated |
NCT04390243 -
Binimetinib and Encorafenib for the Treatment of Pancreatic Cancer in Patients With a Somatic BRAF V600E Mutation
|
Phase 2 | |
Terminated |
NCT03723915 -
Pembrolizumab and Pelareorep in Treating Patients With Advanced Pancreatic Cancer
|
Phase 2 | |
Completed |
NCT03291938 -
IACS-010759 in Advanced Cancers
|
Phase 1 | |
Recruiting |
NCT04539808 -
NeoOPTIMIZE: Early Switching of mFOLFIRINOX or Gemcitabine/Nab-Paclitaxel Before Surgery for the Treatment of Resectable, Borderline Resectable, or Locally-Advanced Unresectable Pancreatic Cancer
|
Phase 2 | |
Active, not recruiting |
NCT01585805 -
Gemcitabine Hydrochloride and Cisplatin With or Without Veliparib or Veliparib Alone in Treating Patients With Locally Advanced or Metastatic Pancreatic Cancer
|
Phase 2 | |
Recruiting |
NCT06454383 -
Gemcitabine and Leflunomide in Patients With Advanced Unresectable Pancreatic Cancer
|
Phase 1 | |
Recruiting |
NCT05038254 -
Enhanced Outpatient Symptom Management to Reduce Acute Care Visits Due to Chemotherapy-Related Adverse Events
|
N/A | |
Recruiting |
NCT05733000 -
CPI-613 (Devimistat) in Combination With Hydroxychloroquine and 5-fluorouracil or Gemcitabine in Treating Patients With Advanced Chemorefractory Solid Tumors
|
Phase 2 | |
Active, not recruiting |
NCT02983578 -
Danvatirsen and Durvalumab in Treating Patients With Advanced and Refractory Pancreatic, Non-Small Cell Lung Cancer, and Mismatch Repair Deficient Colorectal Cancer
|
Phase 2 | |
Completed |
NCT04067960 -
Pharmacogenomics Testing in Directing the Optimal Use of Supportive Care Medications in Patients With Stage III-IV Cancer
|
Early Phase 1 | |
Not yet recruiting |
NCT06381154 -
Photoradiation With Verteporfin to Facilitate Immunologic Activity of Pembrolizumab in Unresectable, Locally Advance or Metastatic Pancreatic Cancer
|
Phase 2 | |
Recruiting |
NCT04115163 -
Biologically Optimized Infusion Schedule of Gemcitabine and Nab-Paclitaxel for the Treatment of Metastatic Pancreatic Cancer
|
Phase 2 |