Selumetinib and Erlotinib Hydrochloride in Treating Patients With Locally Advanced or Metastatic Pancreatic Cancer
Condition: Adenocarcinoma of the Pancreas; Recurrent Pancreatic Cancer; Stage III Pancreatic Cancer; Stage IV Pancreatic Cancer
MeSH terms: Adenocarcinoma; Pancreatic Neoplasms
Intervention: erlotinib hydrochloride; selumetinib; laboratory biomarker analysis
Intervention description: Given PO; Given PO; Correlative studies
Intervention MeSH terms: Erlotinib Hydrochloride
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 46.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well giving selumetinib and erlotinib hydrochloride together
      works in treating patients with locally advanced or metastatic pancreatic cancer that is
      refractory to chemotherapy. Selumetinib and erlotinib hydrochloride may stop the growth of
      cancer cells by blocking some of the enzymes needed for cell growth.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytologically proven adenocarcinoma of the pancreas

          -  Patients must have locally advanced unresectable disease not amenable to curative
             resection or extrapancreatic metastases; patients must have EITHER radiographically
             measurable disease (defined as at least one lesion that can be accurately measured in
             at least one dimension [longest diameter to be recorded] as >= 20 mm with conventional
             techniques or as >= 10 mm with spiral computed tomography [CT] scan) AND/OR a serum
             CA19-9 measurement > 2 x ULN

          -  One prior line of systemic therapy for advanced disease (locally advanced or
             metastatic)

               -  The following represent acceptable examples meeting the definition of one prior
                  line of therapy:

                    -  Gemcitabine as a single agent or in combination with other agents; patients
                       receiving (a) gemcitabine initially alone, with the eventual addition of a
                       second agent; or (b) gemcitabine as part of a combination regimen, followed
                       by gemcitabine alone; are eligible

                    -  A non-gemcitabine-based regimen, including (but not limited to) leucovorin
                       calcium, fluorouracil, irinotecan hydrochloride, and oxaliplatin
                       (FOLFIRINOX) or any combination of components therein

                    -  Treatment as part of a clinical trial involving cytotoxic agents, small
                       molecule inhibitors, monoclonal antibodies, and/or immunomodulatory agents

               -  For patients with locally advanced disease, prior radiation to the primary tumor
                  is allowable as long as there is clear evidence of disease progression (either
                  radiographic locoregional disease progression and/or a rising CA19-9 level);
                  patients may have received chemotherapy both concurrently and/or sequentially
                  with (either before or after) the radiation and still be eligible for the study,
                  as this would be considered all part of the same course of treatment

               -  Treatment given in the adjuvant setting (radiation and/or chemotherapy, given
                  either concurrently or sequentially) does not count as prior therapy as long as
                  progressive disease occurs > 6 months following completion of treatment

          -  Life expectancy of greater than 8 weeks

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

          -  Absolute neutrophil count (ANC) >= 1500/uL

          -  Platelet count >= 100,000/uL

          -  International normalized ratio (INR) =< 1.5 (except those subjects who are receiving
             full-dose warfarin)

          -  Total bilirubin =< 2.0 mg/dL

          -  Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 2.5 times the
             upper limit of normal for subjects

          -  Serum creatinine of =< 2.0 mg/dL

          -  Pregnancy test for women of childbearing potential (serum or urine beta-human
             chorionic gonadotropin [HCG])

          -  All patients must be informed of the investigational nature of this study and must
             sign and give written informed consent in accordance with institutional and federal
             guidelines

          -  Women of child-bearing 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 four weeks after dosing with AZD6244
             ceases; women of child-bearing potential must have a negative pregnancy test prior to
             entry; should a woman become pregnant or suspect she is pregnant while participating
             in this study, she should inform her treating physician immediately; please note that
             the AZD6244 manufacturer recommends that adequate contraception for male patients
             should be used for 16 weeks post-last dose due to sperm life cycle

          -  Ability to understand and the willingness to sign a written informed consent document

        Exclusion Criteria:

          -  Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
             nitrosoureas or mitomycin C) prior to entering the study or those who have not
             recovered from adverse events due to agents administered more than 4 weeks earlier

          -  Patients may not be receiving any other investigational agents

          -  Patients with known brain metastases should be excluded from this clinical trial

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to AZD6244 (or its excipient Captisol) or erlotinib

          -  Previous mitogen-activated protein kinase kinase (MEK) or epidermal growth factor
             receptor (EGFR) inhibitor use

          -  Patients with corrected QT (QTc) interval > 480 msecs or other factors that increase
             the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia,
             family history of long QT interval syndrome) including heart failure that (i) meets
             New York Heart Association (NYHA) class III and IV definitions or (ii) is demonstrated
             by an left ventricular (LV) ejection fraction < 55% on baseline echocardiogram, are
             excluded

          -  Required use of a concomitant medication that can prolong the QT interval

          -  There are potential interactions between erlotinib and cytochrome P450, family 3,
             subfamily A, polypeptide 4 (CYP3A4) inhibitors and CYP3A4 promoters; although caution
             and careful monitoring are recommended when use of these compounds is necessary, use
             of these compounds does not exclude patients from participating in this trial

          -  Refractory nausea and vomiting, chronic gastrointestinal diseases (e.g. inflammatory
             bowel disease), or significant bowel resection that would preclude adequate absorption

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection or psychiatric illness/social situations that would limit compliance with
             study requirements

          -  Pregnant women are excluded from this study; therefore, a negative pregnancy test is
             required for women of childbearing potential; breastfeeding should be discontinued if
             the mother is treated with AZD6244

          -  Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral
             therapy are ineligible