Akt Inhibitor MK2206 in Treating Patients With Advanced Gastric or Gastroesophageal Junction Cancer
Condition: Adenocarcinoma of the Gastroesophageal Junction; Diffuse Gastric Adenocarcinoma; Gastric Intestinal Type Adenocarcinoma; Gastric Mixed Adenocarcinoma; Recurrent Gastric Carcinoma
MeSH terms: Adenocarcinoma; Stomach Neoplasms
Intervention: Akt Inhibitor MK2206
Intervention description: Given PO
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 75.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II clinical trial studies how well Akt inhibitor MK2206 works in treating patients
      with advanced gastric or gastroesophageal junction cancer. Akt inhibitor MK2206 may stop the
      growth of tumor cells by blocking some of the enzymes needed for cell growth.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically or cytologically confirmed adenocarcinoma of the
             stomach or gastroesophageal (GE) junction that has progressed after first-line
             treatment, or is recurrent within 6 months after receiving adjuvant therapy; patients
             must have had exactly one prior systemic treatment regimen; previous adjuvant
             (chemotherapy [chemo]) radiotherapy is permitted; prior chemotherapy given
             concurrently with radiation for radiosensitization is not considered one prior
             systemic regimen

          -  Patients must have measurable disease; computed tomography (CT) scans or magnetic
             resonance imaging (MRIs) used to assess measurable disease must have been completed
             within 28 days prior to registration; CT scans or MRIs used to assess 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 (RECIST 1.1)

          -  Patients must not have known brain metastases

          -  Patients must not have received chemotherapy or radiotherapy within 3 weeks (6 weeks
             for nitrosoureas or mitomycin C) prior to registration

          -  Patient must not have received prior treatment with a phosphatidylinositol 3 (PI3),
             v-akt murine thymoma viral oncogene homolog 1 (AKT) or mechanistic target of rapamycin
             (Mtor) inhibitor for any reason

          -  All toxicities from prior therapy must have resolved to =< grade 1 (Common Terminology
             Criteria for Adverse Events [CTCAE] version 4.0) prior to registration

          -  Patients must not be receiving or planning to receive any other investigational agents

          -  Patients must be able to tolerate oral medications and must not have malabsorption or
             chronic diarrhea (CTCAE version 4.0 grade 2 or higher); administration through a
             feeding tube is not permitted

          -  Hemoglobin >= 9 g/dL

          -  Absolute neutrophil count (ANC) >= 1,500/mcL

          -  Platelets >= 100,000/mcL

          -  Total bilirubin =< institutional upper limit of normal (IULN)

          -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) both =< 2.5 x
             IULN; patients with liver metastases must have AST and ALT =< 5 x IULN

          -  Patients must have adequate kidney function as evidenced by at least ONE of the
             following:

               -  Serum creatinine (mg/dL) =< IULN obtained within 14 days prior to registration

               -  Calculated creatinine clearance > 50 ml/min; the serum creatinine value used in
                  the calculation must have been obtained within 14 days prior to registration

          -  Patients must have international normalized ratio (INR) =< 1.2 unless taking
             therapeutic doses of warfarin; this result must be obtained within 14 days prior to
             registration

          -  Patients must have fasting blood sugar =< 150 mg/dL within 28 days prior to
             registration

          -  Patients must have hemoglobin A1C < 7% within 28 days prior to registration

          -  Patients must have an electrocardiogram (ECG) within 28 days prior to registration;
             patients must have corrected QT interval (QTcF) (by Fridericia's calculation) < 450
             msec (male) or < 470 msec (female)

          -  Patients must have a Zubrod performance status of 0-1

          -  Patient must not have any of the following: a history of congenital long QT syndrome;
             use of concomitant medications that could prolong the QTc interval; New York Heart
             Association class III or IV heart failure; history of myocardial infarction within 6
             months prior to registration; uncontrolled dysrhythmias; poorly controlled angina;
             resting heart rate =< 50 bpm (bradycardia)

          -  Patients must not be receiving concurrent treatment with drugs that are strong
             inducers or inhibitors of cytochrome P450 family 3, subfamily A, polypeptide 4
             (CYP3A4); patients must be able to safely discontinue treatment with these agents for
             >= 2 weeks prior to beginning protocol therapy

          -  Patient must not have 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

          -  Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral
             therapy are ineligible

          -  Patient must not be pregnant or nursing; women/men of reproductive potential must have
             agreed to use two forms of contraception for the duration of protocol treatment and
             for one month after discontinuation of MK-2206; 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 time 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

          -  No other 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

          -  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