Clinical trial NCT06483555: Basal-like PDAC Treated With Gemcitabine, Erlotinib, and Nab-paclitaxel
Official title: Subjects With Advanced Basal-like Pancreatic Adenocarcinoma Treated With Gemcitabine, Erlotinib and Nab-paclitaxel (PANGEA) Versus Subjects With Classical Pancreatic Adenocarcinoma Treated With Triplet Standard of Care Therapy.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Pancreatic Adenocarcinoma
Metastatic Pancreatic Cancer
Basal Cell Neoplasm
Keywords: safety
tolerability
efficacy
EGFR inhibitors
gemcitabine
nab-paclitaxel
Lead sponsor: UNC Lineberger Comprehensive Cancer Center
Sponsor class: OTHER
First posted: 2024-07-03
Enrollment: 104
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Primary outcomes:
measure: Adverse Events per Common Terminology Criteria for Adverse Events (NCI-CTCAE)
timeFrame: First day of study treatment through the 28 days after last treatment
measure: Dose-limiting toxicity (DLT)
timeFrame: Up to 28 days
measure: The objective response rate- basal-like pancreatic carcinoma
timeFrame: Up to 12 weeks
measure: Overall survival- classical metastatic pancreatic adenocarcinoma
timeFrame: 2 years
Secondary outcomes:
measure: The number of Adverse Events (AEs) in subjects with basal like pancreatic carcinoma
timeFrame: First day of study treatment through the 28 days after last treatment
measure: Progression-free survival
timeFrame: 2 years
measure: Overall survival in subjects with basal-like metastatic pancreatic adenocarcinoma
timeFrame: 2 years
measure: The objective response in subjects with classical pancreatic adenocarcinoma
timeFrame: Up to 12 weeks
measure: The number of Adverse Events (AEs) in subjects with classical pancreatic adenocarcinoma
timeFrame: First day of study treatment through the 28 days after last treatment
measure: Progression-free survival (PFS) in subjects with classical pancreatic adenocarcinoma
timeFrame: 2 years
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill Lineberger Comprehensive Cancer Center
state: North Carolina
Study officials:
affiliation: UNC Lineberger Comprehensive Cancer Center
name: Ashwin Somasundaram, MD
role: PRINCIPAL_INVESTIGATOR
References: