Basal-like PDAC Treated With Gemcitabine, Erlotinib, and Nab-paclitaxel

Trial Title: Basal-like PDAC Treated With Gemcitabine, Erlotinib, and Nab-paclitaxel

NCT ID: NCT06483555

Condition: Pancreatic Adenocarcinoma
Metastatic Pancreatic Cancer
Basal Cell Neoplasm

Conditions: Official terms:
Adenocarcinoma
Neoplasms, Basal Cell
Leucovorin
Gemcitabine
Oxaliplatin
Fluorouracil
Irinotecan
Folfirinox
Levoleucovorin

Conditions: Keywords:
safety
tolerability
efficacy
EGFR inhibitors
gemcitabine
nab-paclitaxel

Study type: Interventional

Study phase: Phase 1/Phase 2

Overall status: Not yet recruiting

Study design:

Allocation: Non-Randomized

Intervention model: Parallel Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: Gemcitabine
Description: 1000 mg/m2, intravenously on day 1 and day 15, for subjects with basal-like cell type pancreatic carcinoma.
Arm group label: PurIST Basal

Other name: Gemcitabine hydrochloride

Other name: FF 10832

Other name: LY188011

Other name: C9H11F2N3O4 - HCl

Intervention type: Drug
Intervention name: Nab paclitaxel
Description: 125 mg/m2 intravenously on day 1 and day 15 for subjects with basal-like cell type pancreatic carcinoma.
Arm group label: PurIST Basal

Other name: Abraxane

Intervention type: Drug
Intervention name: Erlotinib
Description: 50 mg per oral daily. for subjects with basal-like cell type pancreatic carcinoma.
Arm group label: PurIST Basal

Other name: Tarceva

Intervention type: Drug
Intervention name: NALIRIFOX
Description: 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.
Arm group label: PurIST Classical

Other name: A combination of liposomal irinotecan,5 fluorouracil /leucovorin and oxaliplatin.

Intervention type: Drug
Intervention name: Folfirinox
Description: Subjects with classical pancreatic adenocarcinoma will receive. Dosing and plan will be decided by the treating physician.
Arm group label: PurIST Classical

Other name: It is a combination of leucovorin calcium (folinic acid), fluorouracil, irinotecan hydrochloride, and oxaliplatin

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.

Detailed description: The standard of care chemotherapy for first-line advanced pancreatic adenocarcinoma is FOLFIRINOX, NALIRIFOX, or gemcitabine/nab-paclitaxel. However, multiple studies suggest that basal-like subtypes of pancreatic adenocarcinoma do not respond to FOLFIRINOX. Based upon existing retrospective analyses, the addition of epidermal growth factor receptor (EGFR) inhibitors such as erlotinib to gemcitabine and nab-paclitaxel suggest improved rates of response in subjects with basal-like pancreatic adenocarcinoma compared to FOLFIRINOX. Subjects with a classical subtype will be treated on standard-of-care oxaliplatin-based triplet chemotherapy. Subjects with basal type will receive the erlotinib combination treatment. The purpose of this study is to find out the best dose of the erlotinib combination treatment. The erlotinib combination treatment is not FDA-approved. However, the combinations of erlotinib, gemcitabine, and nab-paclitaxel are both approved by the FDA for the treatment of pancreatic cancer. The standard of care treatments are both FDA-approved. All three drugs have been used in combination before in other clinical trials and a certain amount of safety data exists. In the basal-like arm of this study, a two-stage utility of bayesian optimal interval ( U-BOIN) design will be used to evaluate the range of safe and admissible doses in Stage 1 and the optimal best dose (OBD) in Stage 2 basal subjects. After the determination of the OBD, an expansion cohort will be enrolled to obtain additional precision of the overall response rate (ORR). In total, 52 patients will be enrolled in the basal-like arm. Separately, 52 patients with "classical" tumors will be enrolled in a parallel arm and given standard-of-care oxaliplatin-based triplet chemotherapy (FOLFIRINOX or NALIRIFOX) to determine long-term outcomes including overall survival, objective response rate, and progression-free survival. This is to test the safety and effectiveness (how well a treatment works) of both treatments, depending on the cancer type.

Criteria for eligibility:
Criteria:
Inclusion Criteria: - Written informed consent was obtained to participate in the study and HIPAA authorization for release of personal health information. Subjects is willing and able to comply with study procedures based on the judgment of the investigator. - Age ≥ 18 years at the time of consent. - Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1 - The subject must consent to a mandatory pre-study biopsy if archival tissue is not available or sufficient. - Subjects 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. Exclusion Criteria: - Disease is not measurable according to Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.1 - Not having histological or cytological evidence/confirmation of metastatic pancreatic adenocarcinoma. - Prior pancreatic-focused therapy. - Brain metastasis diagnosed within the last 4 weeks.

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: University of North Carolina at Chapel Hill Lineberger Comprehensive Cancer Center

Address:
City: Chapel Hill
Zip: 27599
Country: United States

Start date: October 2024

Completion date: August 2026

Lead sponsor:
Agency: UNC Lineberger Comprehensive Cancer Center
Agency class: Other

Source: UNC Lineberger Comprehensive Cancer Center

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06483555
http://unclineberger.org/patientcare/clinical-trials/clinical-trials