Selumetinib and Akt Inhibitor MK2206 or mFOLFOX Therapy Comprising Oxaliplatin and Fluorouracil in Treating Patients With Metastatic Pancreatic Cancer Previously Treated With Chemotherapy
Condition: Pancreatic Acinar Cell Carcinoma; Pancreatic Ductal Adenocarcinoma; Recurrent Pancreatic Carcinoma; Stage IV Pancreatic Cancer
MeSH terms: Carcinoma; Pancreatic Neoplasms; Carcinoma, Acinar Cell
Intervention: Akt Inhibitor MK2206; Fluorouracil; Oxaliplatin; Selumetinib
Intervention description: Given PO; Given IV; Given IV; Given PO
Intervention MeSH terms: Fluorouracil; Oxaliplatin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 137.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase II trial studies how well selumetinib and Akt inhibitor MK2206 work
      compared to modified fluorouracil, leucovorin calcium, and oxaliplatin (mFOLFOX) therapy in
      treating patients with metastatic pancreatic cancer previously treated with chemotherapy.
      Selumetinib and Akt inhibitor MK2206 may stop the growth of tumor cells by blocking some of
      the enzymes needed for cell growth. Drugs used in chemotherapy, such as oxaliplatin, and
      fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the
      cells or by stopping them from dividing. It is not yet know whether selumetinib and Akt
      inhibitor MK2206 are more effective than oxaliplatin and fluorouracil in treating patients
      with metastatic pancreatic cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically or cytologically confirmed diagnosis of pancreatic
             adenocarcinoma; patients with endocrine or neuroendocrine tumors, lymphoma of the
             pancreas, or ampullary cancer are not eligible

          -  Patients must have distant metastatic disease; patients with macroscopic residual
             disease post-resection as the only site of disease are not eligible; patient must not
             have clinically significant ascites (defined as requiring paracentesis) or have brain
             metastases

          -  Patients must have received one line, and no more than one line, of prior
             gemcitabine-based chemotherapy for advanced/metastatic pancreatic cancer and must have
             documentation of metastatic disease progression while on this treatment; documented
             disease progression must occur within 42 days of the last treatment; OR

               -  For patients who received one line of gemcitabine-based chemotherapy for
                  treatment in the adjuvant setting, recurrence to a metastatic site must be
                  documented by imaging studies within 6 months of completing chemotherapy;
                  chemoradiation as part of adjuvant treatment is acceptable; if the patient
                  received one line of adjuvant gemcitabine-based treatment and had disease
                  recurrence after 6 months of completing chemotherapy, patients will only be
                  eligible after failing one additional line of gemcitabine-based chemotherapy used
                  to treat the metastatic disease

          -  Patients must have measurable and/or non-measurable disease; x-rays, scans. or
             physical examinations for assessment of measurable disease must have been completed
             within 28 days prior to registration; x-rays, scans, or other tests for assessment of
             non-measurable disease must have been completed within 42 days prior to registration;
             all disease must be assessed and documented on the Baseline Tumor Assessment Form

          -  Patients must have completed systemic therapy at least 14 days prior to registration,
             any surgical procedure must have been performed at least 14 days prior to
             registration, and radiation therapy must be completed at least 7 days prior to
             registration; patients must have recovered to =< grade 1 from any of the effects of
             prior therapies or procedures

          -  Patients must not plan to receive concurrent chemotherapy, radiotherapy, agents known
             to prolong corrected QT (QTc) interval, or agents known to be strong inducers or
             inhibitors of cytochrome P450 3A4/5 (CYP3A4/5) or cytochrome P450 1A2 (CYP1A2)

          -  Patient must not have received prior treatment with fluorouracil, irinotecan,
             leucovorin calcium, and oxaliplatin (FOLFIRINOX), FOLFOX, oxaliplatin-based
             chemotherapy, mitogen-activated protein kinase (MEK) inhibitors,
             phosphoinositide-3-kinase (PI3K) inhibitors, or protein kinase B (AKT) inhibitors

          -  Zubrod performance status of 0-1

          -  Leukocytes >= 3,000/mcL

          -  Absolute neutrophil count (ANC) >= 1,500/mcL

          -  Platelets >= 100,000/mcL

          -  Hemoglobin >= 9.0 g/dL

          -  Patients must have adequate kidney function as evidenced by at least ONE of the
             following:

               -  Serum creatinine =< 1.5 mg/dL within 14 days prior to registration

               -  Calculated creatinine clearance >= 60 mL/min; the serum creatinine value used in
                  the calculation must have been obtained within 14 days prior to registration

          -  Total bilirubin =< 1.5 times institutional upper limit of normal(IULN)

          -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) both =< 2.5 times
             IULN

          -  Patients must have an albumin level >= 3.0 g/dL within 14 days prior to registration

          -  Patients must have an International Normalized Ratio (INR) =< 1.5 times IULN within 14
             days prior to registration

          -  Patients must have an electrocardiogram (ECG) within 14 days prior to registration;
             patients must have QTcF (by Fridericia's calculation) =< 450 msec (male) or =< 470
             msec (female)

          -  Patients with baseline neuropathy must be =< grade 1 according to Common Terminology
             Criteria for Adverse Events (CTCAE) v 4.0

          -  Patients must not have uncontrolled diarrhea or active infection requiring antibiotics
             and be fully recovered from any previous serious infections within 7 days prior to
             registration

          -  Patients must be able to swallow tablets and capsules

          -  Patients with diabetes must be well controlled with fasting glucose =< grade 1
             according to CTCAE v 4.0 within 14 days prior to registration

          -  Patients with history of congestive heart failure must have an ejection fraction >=
             55% within 14 days prior to registration

          -  Patients must not have any of the following: uncontrolled hypertension, acute coronary
             syndrome within 6 months prior to registration, poorly controlled angina, New York
             Heart Association class II-IV heart failure, prior or current cardiomyopathy, atrial
             fibrillation, or severe valvular heart disease

          -  Patients must not have a current or past history of central serous retinopathy,
             retinal vein occlusion, retinal detachment, or have uncontrolled glaucoma
             (irrespective of intraocular pressure [IOP])

          -  No prior malignancy is allowed except for the following: adequately treated basal cell
             or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or
             II cancer from which the patient is currently in complete remission, or any other
             cancer from which the patient has been disease-free for five years

          -  Patients must not be pregnant or nursing; women/men of reproductive potential must
             have agreed to use an effective contraceptive method during the study plus at least 16
             weeks after last dose; a woman is considered to be of "reproductive potential" if she
             has had menses at any time in the preceding 12 consecutive months; in addition to
             routine contraceptive methods, "effective contraception" also includes heterosexual
             celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy
             prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal
             ligation; however, if at any point a previously celibate patient chooses to become
             heterosexually active during the time period for use of contraceptive measures
             outlined in the protocol, he/she is responsible for beginning contraceptive measures

          -  Prestudy history and physical must be obtained within 28 days prior to registration

          -  Sites must seek additional patient consent for the future use of specimens

          -  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

          -  As part of the Oncology Patient Enrollment Network (OPEN) registration process the
             treating institution's identity is provided in order to ensure that the current
             (within 365 days) date of institutional review board approval for this study has been
             entered into the system