Basal-like PDAC Treated With Gemcitabine, Erlotinib, and Nab-paclitaxel
NCT Number: NCT06483555
Acronym: PANGEA
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE1|PHASE2
Conditions: Pancreatic Adenocarcinoma|Metastatic Pancreatic Cancer|Basal Cell Neoplasm
Interventions: DRUG: Gemcitabine|DRUG: Nab paclitaxel|DRUG: Erlotinib|DRUG: NALIRIFOX|DRUG: Folfirinox
Sponsor: UNC Lineberger Comprehensive Cancer Center
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 104
Study Design: Allocation: NON_RANDOMIZED|Intervention Model: PARALLEL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-08
Completion Date: 2026-08
Locations: University of North Carolina at Chapel Hill Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina, 27599, United States

Summary:
This study explores the best dose of the combination treatment for subjects with advanced unresectable or metastatic basal-like subtype pancreatic adenocarcinoma. For that reason, the safety, efficacy, and tolerability, as well as preliminary estimates of anti-tumor effects of low-dose epidermal growth factor receptor EGFR inhibitors in combination with bi-weekly gemcitabine/nab-paclitaxel (GnP) will be examined in subjects with advanced basal-like pancreatic adenocarcinoma.

The Purity Independent Subtyping of Tumors (PurIST) will determine the type of cancer either "basal type" or "classical". If cancer subtype-based first-line chemotherapy in combination with erlotinib will be safe and tolerable in subjects with advanced unresectable or metastatic pancreatic adenocarcinoma of the basal-like subtype as defined by PurIST, as well as provide a preliminary assessment of treatment response in basal-like subjects. This study will also follow a subset of subjects with classical subtypes that are treated per standard of care on oxaliplatin-based triplet chemotherapy.

Primary Outcome Measures: Adverse Events per Common Terminology Criteria for Adverse Events (NCI-CTCAE), Adverse Events (AEs) will be classified and graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0, in Phase I subjects with basal-like settings. The number of participants with adverse events (AE) will be reported.

., First day of study treatment through the 28 days after last treatment|Dose-limiting toxicity (DLT), DLTs are defined using adverse events as at least possibly related to erlotinib administration in Phase I subjects. If an apparent DLT is clearly due to an underlying disease and is unrelated to the product infusion, then the investigator will specify that the event is not a DLT. Toxicities related to treatment and assessed Adverse Events per Common Terminology Criteria for Adverse Events (NCI-CTCAE) will be used for assessment.

The safety evaluation period for dose-limiting toxicity (DLT) assessment and determination of optimal best dose (OBD) will encompass toxicities related to treatment with low-dose erlotinib when administered with bi-weekly gemcitabine/nab-paclitaxel starting on the day of treatment initiation through the end of treatment., Up to 28 days|The objective response rate- basal-like pancreatic carcinoma, The objective response rate in Stage 2 subjects with basal-like histology, treated with low-dose erlotinib at the OBD when administered with bi-weekly gemcitabine/nab-paclitaxel as defined as complete response (CR) + partial response (PR) as determined by Response Evaluation Criteria In Solid Tumors Criteria (RECIST) 1.1 criteria. RECIST indicates if the subject experienced a Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), no response or less response than Partial or Progressive; or Progressive Disease (PD), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions., Up to 12 weeks|Overall survival- classical metastatic pancreatic adenocarcinoma, Overall survival of subjects with classical metastatic pancreatic adenocarcinoma is defined as the length of time from the start of treatment until death., 2 years
Secondary Outcome Measures: The number of Adverse Events (AEs) in subjects with basal like pancreatic carcinoma, The number of Adverse Events (AEs) in subjects with basal-like pancreatic carcinoma treated with low-dose erlotinib when administered with bi-weekly gemcitabine/nab-paclitaxel as defined by CTCAE v5., First day of study treatment through the 28 days after last treatment|Progression-free survival, Progression-free survival in subjects on low-dose erlotinib when administered with bi-weekly gemcitabine/nab-paclitaxel with basal-like metastatic pancreatic adenocarcinoma is defined as the length of time between the start of treatment until progression or death., 2 years|Overall survival in subjects with basal-like metastatic pancreatic adenocarcinoma, Overall survival in subjects with basal-like metastatic pancreatic adenocarcinoma on low-dose erlotinib when administered with bi-weekly gemcitabine/nab-paclitaxel is defined as the length of time from the start of treatment until death (basal-like arm only)., 2 years|The objective response in subjects with classical pancreatic adenocarcinoma, The objective response in subjects with classical pancreatic adenocarcinoma treated with standard-of-care triplet chemotherapy (FOLFIRINOX or NALIRIFOX) as defined as complete response (CR) + partial response (PR) as determined by RECIST 1.1 criteria., Up to 12 weeks|The number of Adverse Events (AEs) in subjects with classical pancreatic adenocarcinoma, The number of Adverse Events (AEs) in subjects with classical pancreas carcinoma treated with standard-of-care triplet therapy as defined by CTCAE v5.0., First day of study treatment through the 28 days after last treatment|Progression-free survival (PFS) in subjects with classical pancreatic adenocarcinoma, Progression-free survival (PFS) after standard-of-care triplet chemotherapy (FOLFIRINOX or NALIRIFOX) in patients with classical metastatic pancreatic adenocarcinoma is defined as the length of time between the start of standard-of-care triplet therapy until progression or death., 2 years