Erlotinib, Gemcitabine and Nab-Paclitaxel for the Treatment of Metastatic Basal-Like Pancreatic Cancer, PANGEA Trial

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 known 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 (patients with pancreatic cancer [PC] do not typically develop brain metastasis, therefore this should not be evaluated per MRI at screening).
• 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 per treating physician 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 (or any combination of the previous three regiments, such as folinic acid, fluorouracil, and irinotecan hydrochloride [FOLFIRI], folinic acid, fluorouracil, and oxaliplatin [FOLFOX], etc) 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 ≥ 75 × 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 (or any combination of the previous three regiments, such as FOLFIRI, FOLFOX, etc). 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. This only applies to subjects receiving erlotinib.