Akt Inhibitor MK2206 in Treating Patients With Advanced Gastric or Gastroesophageal Junction Cancer

Inclusion Criteria:

• Histologically or cytologically confirmed adenocarcinoma of the stomach or gastroesophageal (GE) junction

  • Disease that has progressed after first-line regimen or is recurrent within the past 6 months after adjuvant therapy
• Measurable disease by CT scans or MRI within the past 28 days
• No known brain metastases
• Zubrod performance status 0-1
• ANC ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Hemoglobin ≥ 9 g/dL
• Bilirubin normal
• AST and ALT ≤ 2.5 times upper limit of normal (ULN) (≤ 5.0 times ULN for patients with liver metastases)
• Serum creatinine ≤ ULN OR creatinine clearance > 50 mL/min
• INR ≤ 1.2 (unless taking therapeutic warfarin)
• Fasting blood sugar ≤ 150 mg/dL
• Hemoglobin A1C < 7%
• QTcF < 450 msec (male) or QTcF < 470 msec (female)
• Patient must not be pregnant or nursing because of the risk of fetal or infant harm; 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

• Able to tolerate oral medications

  • No malabsorption or chronic diarrhea (≥ grade 2)
  • No feeding tube

• None of the following:

  • History of congenital long QT syndrome
  • NYHA class III or IV heart failure
  • History of myocardial infarction within the past 6 months
  • Uncontrolled dysrhythmia
  • Poorly controlled angina
  • Resting heart rate ≤ 50 bpm (bradycardia)

• No uncontrolled intercurrent illness including, but not limited to, any of the following:

  • Ongoing or active infection
  • Symptomatic congestive heart failure
  • Unstable angina pectoris
  • Cardiac arrhythmia
  • Psychiatric illness and/or social situations that would limit compliance with study requirements
• More than 5 years since another malignancy except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or adequately treated stage I or II cancer for which the patient is currently in complete remission

• No concurrent radiotherapy except local radiotherapy for bone pain

  • Lesions within the irradiated field cannot be used for response assessment
• Recovered to ≤ grade 1 toxicities from prior therapy

• Prior adjuvant chemotherapy and/or radiotherapy allowed

  • Prior chemotherapy with radiotherapy not considered 1 prior regimen
• More than 3 weeks since prior chemotherapy or radiotherapy (6 weeks for nitrosoureas or mitomycin C)
• No prior PI3, AKT, or Mtor inhibitor for any reason
• At least 2 weeks since prior and no concurrent drugs that are strong inducers or inhibitors of CYP3A4
• No concurrent or plan to receive any other investigational agents
• No concurrent medications that could prolong the QTc interval
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No other concurrent chemotherapy