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

• Progression-free survival of patients treated with Akt inhibitor MK2206 [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
• Response rate (confirmed and unconfirmed complete and partial response) according to RECIST 1.1 [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
• Frequency and severity of toxicity incidents assessed by Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]

• Progression-free survival of patients treated with Akt inhibitor MK2206 [ Designated as safety issue: No ]
• Response rate (complete or partial response) in patients treated with Akt inhibitor MK2206 according to RECIST [ Designated as safety issue: No ]
• Toxicity of Akt inhibitor MK2206 [ Designated as safety issue: Yes ]

This phase II clinical trial is studying 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.

PRIMARY OBJECTIVES:

I. To estimate the overall survival (OS) for patients with advanced gastric and gastroesophageal junction (GEJ) adenocarcinoma treated with MK-2206.

II. To estimate the progression free survival (PFS) in this patient population. III. To estimate the response rate (confirmed and unconfirmed CR and PR by RECIST 1.1) in this patient population.

IV. To assess the frequency and severity of toxicity associated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive Akt inhibitor MK2206 orally (PO) once daily, every other day, for 28 days. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed up every 3 months for 2 years.

• Adenocarcinoma of the Gastroesophageal Junction
• Adenocarcinoma of the Stomach
• Recurrent Esophageal Cancer
• Recurrent Gastric 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