BVD-523 Plus Nab-paclitaxel and Gemcitabine in Patients With Metastatic Pancreatic Cancer
Condition: Pancreatic Cancer; Cancer of Pancreas; Cancer of the Pancreas; Pancreas Cancer
MeSH terms: Pancreatic Neoplasms
Intervention: BVD-523; Nab-paclitaxel; Gemcitabine; Tumor biopsy
Intervention MeSH terms: Paclitaxel; Albumin-Bound Paclitaxel; Gemcitabine
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 18.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      In light of the central role of extracellular signal-regulated kinases (ERK) in pancreatic
      cancer, the investigators propose a phase I study to evaluate the ERK inhibitor BVD-523 at
      the recommended phase 2 dose in combination with nab-paclitaxel plus gemcitabine in patients
      with newly diagnosed metastatic pancreatic cancer. The primary endpoint will be maximum
      tolerated dose (MTD) or RP2D and safety. The secondary endpoints include safety, response
      rate, biochemical response, progression-free survival (PFS) and overall survival (OS). The
      exploratory endpoints include the assessing the impact of BVD-523 on the MEK/ERK pathway and
      other major pathway pertain to pancreatic cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytologically confirmed newly diagnosed treatment-naïve metastatic
             adenocarcinoma of the pancreas with metastatic disease diagnosed no more than 6 weeks
             prior to enrollment. Patients with advanced pancreatic cancer progressed on 5-FU (or
             capecitabine) based regimen will be allowed in the expansion cohort.

          -  Measurable disease defined as lesions that can be accurately measured in at least one
             dimension (longest diameter to be recorded) as ≥ 10 mm with CT scan or MRI, as ≥ 20 mm
             by chest x-ray, or ≥ 10 mm with calipers by clinical exam.

          -  At least 18 years of age.

          -  Life expectancy > 3 months.

          -  ECOG performance status ≤ 1

          -  Normal bone marrow and organ function as defined below:

               -  Absolute neutrophil count ≥ 1,500/mcL

               -  Platelets ≥ 100,000/mcL

               -  Hemoglobin ≥ 9.0 g/dL

               -  Total bilirubin ≤ IULN

               -  AST(SGOT)/ALT(SGPT) ≤ 2.5 x IULN, unless there are liver metastases in which case
                  AST and ALT ≤ 5.0 x IULN

               -  Creatinine ≤ 1.5 x IULN OR GFR of ≥ 50 mL/min

               -  Cardiac function ≥ ILLN, e.g., LVEF of > 50% as assessed by MUGA or ECHO, QTc <
                  470 ms

          -  Women of childbearing potential and men must agree to use adequate contraception
             (hormonal or barrier method of birth control, abstinence) prior to study entry, for
             the duration of study participation, and for three months following study
             discontinuation. Should a woman become pregnant or suspect she is pregnant while
             participating in this study, she must inform her treating physician immediately.

          -  Ability to understand and willingness to sign an IRB approved written informed consent
             document (or that of legally authorized representative, if applicable).

        Exclusion Criteria:

          -  Current use or anticipated need for alternative, holistic, naturopathic, or botanical
             formulations used for the purpose of cancer treatment.

          -  A history of other malignancy with the exception of those treated with curative intent
             with no evidence of disease for 2 years.

          -  Currently receiving any other investigational agents.

          -  Known brain metastases or CNS involvement.

          -  Significant ascites that require therapeutic paracentesis.

          -  A history of allergic reactions attributed to compounds of similar chemical or
             biologic composition to BVD-523, gemcitabine, nab-paclitaxel, or other agents used in
             the study.

          -  Neuropathy ≥ grade 2.

          -  History or current evidence/risk of retinal vein occlusion (RVO) or central serous
             retinopathy (CSR).

          -  History of interstitial lung disease or pneumonitis.

          -  Concurrent therapy with drugs known to be strong inhibitors of CYP1A2, CYP2D6, and
             CYP3A4, or strong inducers of CYP3A4 (see Appendix B).

          -  Gastrointestinal condition which could impair absorption of BVD-523 or inability to
             ingest BVD-523.

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements.

          -  Pregnant and/or breastfeeding. Women of childbearing potential must have a negative
             pregnancy test within 7 days of study entry.

          -  Known HIV-positivity.