Erlotinib, Gemcitabine and Nab-Paclitaxel for the Treatment of Metastatic Basal-Like Pancreatic Cancer, PANGEA Trial
This phase I/II trial tests the side effects and best dose of erlotinib when given together with gemcitabine and nab-paclitaxel, and to see how well it works in treating patients with basal-like pancreatic cancer that has spread from where it first started to other places in the body (metastatic). Erlotinib is in a class of medications called kinase inhibitors. It works by blocking the action of a protein called epidermal growth factor receptor (EGFR) that signals tumor cells to multiply. This helps slow or stop the spread of tumor cells. Gemcitabine is a chemotherapy drug that blocks the cells from making deoxyribonucleic acid (DNA) and may kill tumor cells. Paclitaxel is in a class of medications called antimicrotubule agents. It stops tumor cells from growing and dividing and may kill them. Nab-paclitaxel is an albumin-stabilized nanoparticle formulation of paclitaxel which may have fewer side effects and work better than other forms of paclitaxel. Giving erlotinib, gemcitabine and nab-paclitaxel may work better than standard chemotherapy in treating patients with metastatic basal-like pancreatic cancer.
Inclusion Criteria
- Written informed consent obtained to participate in the study and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information. Subjects is willing and able to comply with study procedures based on the judgement of the investigator.
- Age ≥ 18 years at the time of consent.
- Eastern Cooperative Oncology Group (ECOG) or Karnofsky performance status of 0-1.
- Histological or cytological evidence/confirmation of unresectable, borderline resectable, or metastatic (basal-like and classical) pancreatic adenocarcinoma. Patients with suspicion of disease based on previous imaging or laboratory results will undergo diagnostic biopsy
- Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1.
- The subject must consent to a mandatory pre-study biopsy if archival tissue is not available or sufficient as well as a mandatory biopsy after Cycle 3 but before Cycle 4 for subjects on basal-like arm
- A subject with prior brain metastasis may be considered if they have completed their treatment for brain metastasis at least 4 weeks prior to study treatment have been off of corticosteroids for ≥ 2 weeks and are asymptomatic.
- 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.
- Subjects may have received prior standard-of-care (SOC) neoadjuvant/adjuvant/perioperative therapy and may have received up to two cycles of first-line FOLFIRINOX or NALIRIFOX or GnP in the advanced setting. Subjects must not have received any chemotherapy within 28 days prior to enrollment, except for up to two cycles of FOLFIRINOX, NALIRIFOX, or GnP which ARE allowed during this timeframe even prior to screening or consent for this study
- PurIST BASAL ONLY: Hemoglobin (Hgb) ≥ 8 g/dL (within 28 days prior to initiating study treatment).
- PurIST BASAL ONLY: White blood cell (WBC) ≥ 2.0 × 10^9/L (within 28 days prior to initiating study treatment).
- PurIST BASAL ONLY: Absolute neutrophil count (ANC) ≥ 1.0 × 10^9/L (within 28 days prior to initiating study treatment).
- PurIST BASAL ONLY: Platelets ≥ 100 × 10^9/L (within 28 days prior to initiating study treatment).
- PurIST BASAL ONLY: Creatinine ≤ 1.5 × upper limit of normal (ULN) OR calculated creatinine clearance ≥ 45 mL/min using the Cockcroft-Gault formula (within 28 days prior to initiating study treatment).
- PurIST BASAL ONLY: Bilirubin ≤ 2 × ULN. Subjects with Gilbert’s syndrome may be enrolled despite a total bilirubin level > 1.5 mg/dL if their conjugated bilirubin is < 1.5 × ULN (within 28 days prior to initiating study treatment).
- PurIST BASAL ONLY: Aspartate aminotransferase (AST) ≤ 3 × ULN (within 28 days prior to initiating study treatment).
- PurIST BASAL ONLY: Alanine aminotransferase (ALT) ≤ 3 × ULN (within 28 days prior to initiating study treatment).
- PurIST BASAL ONLY: International normalized ratio (INR) or prothrombin time (PT) activated partial thromboplastin time (aPTT) ≤ 2 × ULN unless on anticoagulation in which case this can be ignored (within 28 days prior to initiating study treatment).
- Note: Hematology and other lab parameters that are ≥ grade 2 BUT still meet criteria for study entry are allowed. Furthermore, changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy
- Subjects with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association functional classification. To be eligible for this trial, subjects should be class 2B or better.
- Females of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to study treatment. NOTE: Females are considered of childbearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months. Documentation of postmenopausal status must be provided.
- Females of childbearing potential must be willing to abstain from heterosexual activity or to use 2 forms of effective methods of contraception from the time of informed consent until 6 months after treatment discontinuation. The two contraception methods can be comprised of two barrier methods, or a barrier method plus a hormonal method or an intrauterine device that meets < 1% failure rate for protection from pregnancy in the product label.
- Male subjects with female partners must have had a prior vasectomy or agree to use an adequate method of contraception (i.e., double barrier method: condom plus spermicidal agent) starting with the first dose of study therapy through 6 months after the last dose of study therapy.
Exclusion Criteria
- Active infection requiring systemic therapy.
- Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
- Treatment with any investigational drug or prior cancer treatment within 28 days prior to study treatment, except for up to two cycles of first-line FOLFIRINOX, NALIRIFOX, or GnP. The subject must have recovered from all reversible acute toxic effects of the regimen (other than alopecia) to ≤ grade 1 or baseline prior to initiating study treatment.
- Subject is currently using tobacco products or vaping. Unless the subject agrees to be on a cessation program during the study treatment.
- Untreated hepatitis B virus (HBV) may be eligible for study if positive but under physicians treatment (screening is NOT required unless mandated by local health authority)
- Other exclusion criteria as specified by drug manufacturer including existing interstitial lung disease, hepatic failure, severe existing myelosuppression, history of hemolytic-uremic syndrome or other microangiopathic hemolytic anemia, history of posterior reversible encephalopathy syndrome, existing bullous/exfoliative skin disorders, severe renal impairment, recent myocardial infarction or cerebrovascular accident within three months.
- Subject is receiving prohibited medications or treatments that cannot be discontinued/replaced by an alternative therapy within 28 days of initiating treatment.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT06483555.
Locations matching your search criteria
United States
North Carolina
Chapel Hill
PRIMARY OBJECTIVES:
I. To determine the optimal biologic dose (OBD) of low-dose erlotinib when administered with bi-weekly gemcitabine/nab-paclitaxel (GnP) in subjects with basal-like (defined by Purity Independent Subtyping of Tumors [PurIST]) metastatic pancreatic adenocarcinoma in the first-line setting. (Phase I)
II. To estimate progression-free survival (PFS) after study treatment (low-dose erlotinib when administered with bi-weekly GnP) in patients with basal-like metastatic pancreatic adenocarcinoma (defined by PurIST) in the first-line setting, overall, by dose level, by stage. (Phase II)
III. To estimate 1-year overall survival (OS) in subjects classical metastatic pancreatic adenocarcinoma (as determined by PurIST) treated (1) per standard of care oxaliplatin-based triplet chemotherapy (leucovorin calcium [folinic acid], fluorouracil, irinotecan hydrochloride, and oxaliplatin [FOLFIRINOX] or liposomal irinotecan, fluorouracil, leucovorin, and oxaliplatin [NALIRIFOX]), (2) with gemcitabine/nab-paclitaxel (GnP) or (3) enrolled onto an applicable clinical trial in the first-line setting. (Phases I and II)
SECONDARY OBJECTIVES:
I. To describe the adverse events associated with low-dose erlotinib when administered with bi-weekly gemcitabine/nab-paclitaxel in subjects with basal-like (defined by PurIST) metastatic pancreatic adenocarcinoma in the first-line setting, overall and by dose level, and by stage.
II. To estimate the objective response rate (ORR) for low-dose erlotinib when administered with bi-weekly gemcitabine/nab-paclitaxel in subjects with basal-like (defined by PurIST) metastatic pancreatic adenocarcinoma in the first-line setting at the OBD from the expansion cohort in the basal-like arm.
III. To estimate overall survival (OS) after study treatment (low-dose erlotinib when administered with bi-weekly gemcitabine/nab-paclitaxel) in subjects with basal-like metastatic pancreatic adenocarcinoma (defined by PurIST) in the first-line setting, overall, by dose level, and by stage.
IV. To estimate the objective response rate (ORR) in subjects with classical metastatic pancreatic adenocarcinoma (as defined by PurIST) treated (1) per standard of care oxaliplatin-based triplet chemotherapy (FOLFIRINOX or NALIRIFOX), (2) with gemcitabine/nab-paclitaxel (GnP) or (3) enrolled onto an applicable clinical trial in the first-line setting, overall and by treatment type.
V. To describe the adverse events in subjects with classical metastatic pancreatic adenocarcinoma (as defined by PurIST) in the first-line setting associated with treated (1) per standard of care oxaliplatin-based triplet chemotherapy (FOLFIRINOX or NALIRIFOX), (2) with gemcitabine/nab-paclitaxel (GnP) or (3) enrolled onto an applicable clinical trial, overall and by treatment type.
VI. To estimate progression-free survival (PFS) in subjects with classical metastatic pancreatic adenocarcinoma (as defined by PurIST) in the first-line setting treated (1) per standard of care oxaliplatin-based triplet chemotherapy (FOLFIRINOX or NALIRIFOX), (2) with gemcitabine/nab-paclitaxel (GnP) or (3) enrolled onto an applicable clinical trial, overall and by treatment type.
EXPLORATORY OBJECTIVES:
I. To evaluate the tumor microenvironment of subjects receiving low-dose erlotinib when administered with bi-weekly gemcitabine/nab-paclitaxel in subjects with basal-like metastatic pancreatic adenocarcinoma in the first-line setting, overall, by dose level, by phase.
II. To examine markers identified in the tumor microenvironment in circulating free deoxyribonucleic acid (cfDNA) collected from subjects receiving low-dose erlotinib when administered with bi-weekly gemcitabine/nab-paclitaxel in subjects with basal-like (defined by PurIST) metastatic pancreatic adenocarcinoma in the first-line setting, overall, by dose level, by phase.
III. To evaluate the tumor microenvironment of subjects receiving (1) standard of care oxaliplatin-based triplet chemotherapy (FOLFIRINOX or NALIRIFOX), (2) gemcitabine/nab-paclitaxel (GnP) or (3) enrolling on a clinical trial with classical (defined by PurIST) metastatic pancreatic adenocarcinoma in the first-line setting overall and by treatment type.
IV. To examine markers identified in the tumor microenvironment in cfDNA collected from subjects treated (1) per standard of care oxaliplatin-based triplet chemotherapy (FOLFIRINOX or NALIRIFOX), (2) with gemcitabine/nabpaclitaxel (GnP) or (3) enrolled on a clinical trial with classical (defined by PurIST) metastatic pancreatic adenocarcinoma in the first-line setting, overall and by treatment type.
V. To evaluate treatment and survival outcomes based upon KRAS mutant type and KRAS-wild type (WT) status, as well as homologous recombination deficiency (HRD) mutation status.
OUTLINE:
SCREENING: Patients undergo tissue testing using PurIST to determine pancreatic cancer type during screening.
TREATMENT: This is a phase 1, dose-escalation study of erlotinib in combination with gemcitabine and nab-paclitaxel (Arm A only) followed by a phase 2 dose-expansion study.
PHASE 1: Patients are assigned to Arm I or Arm II.
ARM I: Patients with basal-like pancreatic adenocarcinoma receive erlotinib orally (PO) once daily (QD), gemcitabine intravenously (IV) over 30-40 minutes on days 1 and 15 and nab-paclitaxel IV over 30-40 minutes on days 1 and 15 of each cycle. Cycles repeat every 28 days for up to 60 cycles in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo computed tomography (CT) scan or magnetic resonance imaging (MRI) and blood sample collection throughout the study. Patients may also undergo biopsy during screening and optionally on study.
ARM II: Patients with classical pancreatic adenocarcinoma receive standard of care (SOC) chemotherapy with FOLFIRINOX, NALIRIFOX or GnP per physician discretion, in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT scan or MRI and blood sample collection throughout the study. Patients may also undergo biopsy during screening and optionally on study.
PHASE 2: Patients are assigned to Arm III or Arm IV.
ARM III: Patients are randomized to 1 of 2 arms.
* ARM IIIA: Patients with basal-like pancreatic adenocarcinoma receive erlotinib PO QD gemcitabine IV over 30-40 minutes on days 1 and 15 and nab-paclitaxel IV over 30-40 minutes on days 1 and 15 of each cycle. Cycles repeat every 28 days for up to 60 cycles in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT scan or MRI and blood sample collection throughout the study. Patients may also undergo biopsy during screening and optionally on study.
* ARM IIIB: Patients with basal-like pancreatic adenocarcinoma receive gemcitabine IV over 30-40 minutes on days 1 and 15 and nab-paclitaxel IV over 30-40 minutes on days 1 and 15 of each cycle. Cycles repeat every 28 days for up to 60 cycles in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT scan or MRI and blood sample collection throughout the study. Patients may also undergo biopsy during screening and optionally on study.
ARM IV: Patients with classical pancreatic adenocarcinoma receive SOC chemotherapy with FOLFIRINOX, NALIRIFOX or GnP as in Arm II above. Additionally, patients undergo CT scan or MRI and blood sample collection throughout the study. Patients may also undergo biopsy during screening and optionally on study.
After completion of study treatment, patients are followed for 12 months.
Trial PhasePhase I/II
Trial Typetreatment
Lead OrganizationUNC Lineberger Comprehensive Cancer Center
Principal InvestigatorAshwin Somasundaram
- Primary IDLCCC2220
- Secondary IDsNCI-2025-00301
- ClinicalTrials.gov IDNCT06483555