This Phase I/II clinical trial is being conducted at multiple centers to find out whether adding a low dose of EGFR blocking drugs to the standard chemotherapy combination of gemcitabine and nab paclitaxel (GnP) is safe, tolerable, and helpful for people with advanced pancreatic cancer. All participants are first tested with a tool called PurIST, which classifies tumors as either "basal-like" or "classical." People with basal-like tumors will receive GnP plus erlotinib during Phase I so researchers can determine the safest and most effective dose. Once that dose is identified, the study moves to Phase II, where people with basal-like tumors will be randomly assigned to receive either GnP alone or GnP with erlotinib. Phase II may also test new drug combinations if new treatments become approved during the study period. Overall, the trial plans to include up to about 52 basal-like patients in Phase I, roughly 82 basal-like patients in Phase II, and at least 52 classical patients, with the possibility of enrolling more if needed. People whose tumors are classified as classical will continue with standard treatments recommended by their doctors or other clinical trials. Across the entire study, researchers will carefully track long-term outcomes such as overall survival, how long patients live before the cancer progresses, and how well their tumors respond to treatment.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
104
1000 mg/m2, intravenously on day 1 and day 15, for subjects with basal-like cell type pancreatic carcinoma.
125 mg/m2 intravenously on day 1 and day 15 for subjects with basal-like cell type pancreatic carcinoma.
50 mg per oral daily. for subjects with basal-like cell type pancreatic carcinoma.
Subjects with classical pancreatic adenocarcinoma will receive. NALIRIFOX is liposomal irinotecan with 5-fluorouracil/leucovorin and oxaliplatin. Dosing and plan will be decided by the treating physician.
Subjects with classical pancreatic adenocarcinoma will receive. Dosing and plan will be decided by the treating physician.
University of North Carolina at Chapel Hill Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, United States
RECRUITINGAdverse 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. .
Time frame: 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.
Time frame: Up to 28 days
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.
Time frame: 2 years
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.
Time frame: 2 years
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.
Time frame: First day of study treatment through the 28 days after last treatment
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).
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 2 years
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.
Time frame: Up to 12 weeks
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