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

NCT ID: NCT06483555

Last Updated: 2025-04-16

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 104 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-02-06
• Study Completion Date: 2027-08-31

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.

Conditions

Pancreatic Adenocarcinoma; Metastatic Pancreatic Cancer; Basal Cell Neoplasm

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

PurIST Basal

Subjects will be screened using the PurIST classifier and "basal-like" tumors will be assigned combination therapy with GnP and erlotinib.

Group Type: EXPERIMENTAL

Gemcitabine

Intervention Type: DRUG

1000 mg/m2, intravenously on day 1 and day 15, for subjects with basal-like cell type pancreatic carcinoma.

Nab paclitaxel

Intervention Type: DRUG

125 mg/m2 intravenously on day 1 and day 15 for subjects with basal-like cell type pancreatic carcinoma.

Erlotinib

Intervention Type: DRUG

50 mg per oral daily. for subjects with basal-like cell type pancreatic carcinoma.

PurIST Classical

Subjects will be screened using the PurIST classifier and with classical tumors will be treated per standard of care on triplet therapy.

Group Type: ACTIVE_COMPARATOR

NALIRIFOX

Intervention Type: DRUG

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.

Folfirinox

Intervention Type: DRUG

Subjects with classical pancreatic adenocarcinoma will receive. Dosing and plan will be decided by the treating physician.

Interventions

Gemcitabine

1000 mg/m2, intravenously on day 1 and day 15, for subjects with basal-like cell type pancreatic carcinoma.

Intervention Type: DRUG

Nab paclitaxel

125 mg/m2 intravenously on day 1 and day 15 for subjects with basal-like cell type pancreatic carcinoma.

Intervention Type: DRUG

Erlotinib

50 mg per oral daily. for subjects with basal-like cell type pancreatic carcinoma.

Intervention Type: DRUG

NALIRIFOX

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.

Intervention Type: DRUG

Folfirinox

Subjects with classical pancreatic adenocarcinoma will receive. Dosing and plan will be decided by the treating physician.

Intervention Type: DRUG

Other Intervention Names

Gemcitabine hydrochloride; FF 10832; LY188011; C9H11F2N3O4 - HCl; Abraxane; Tarceva; A combination of liposomal irinotecan,5 fluorouracil /leucovorin and oxaliplatin.; It is a combination of leucovorin calcium (folinic acid), fluorouracil, irinotecan hydrochloride, and oxaliplatin

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

UNC Lineberger Comprehensive Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ashwin Somasundaram, MD

Role: PRINCIPAL_INVESTIGATOR

UNC Lineberger Comprehensive Cancer Center

Locations

University of North Carolina at Chapel Hill Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Catherine A Griffin

Role: CONTACT

catherine_griffin@med.unc.edu

1 984-974-8771

Facility Contacts

Catherine A Griffin

Role: primary

catherine_griffin@med.unc.edu

984-974-8771

Related Links

http://unclineberger.org/patientcare/clinical-trials/clinical-trials

University of North Carolina Lineberger Comprehensive Cancer Center Clinical Trials

Other Identifiers

LCCC2220

Identifier Type: -

Identifier Source: org_study_id