Akt Inhibitor MK2206 in Treating Patients With Previously Treated Colon or Rectal Cancer That is Metastatic or Cannot Removed by Surgery

Inclusion Criteria:

• Patients must have histologically confirmed, radiologically measurable metastatic or unresectable colorectal adenocarcinoma that is amenable to image-guided biopsy and for which standard curative or palliative measures do not exist or are no longer effective; disease in previously radiated regions may not be considered measurable unless there has been demonstrated progression in the lesion
• Patients must have failed available therapy for the treatment of advanced colorectal cancer; this is defined as progressive disease during or within 6 months after fluoropyrimidine, irinotecan, oxaliplatin, bevacizumab, and for v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) wild-type patients, anti-epidermal growth factor receptor (EGFR) antibody (cetuximab or panitumumab) containing therapies, with most recent progression by Response Evaluation Criteria in Solid Tumors (RECIST) criteria; patients who had at least stable disease as best response on their prior therapies (listed above) should have received at least 2 months (approximately 60 days) of treatment; for oxaliplatin-based therapy, failure of therapy will also include patients who progressed within 12 months of adjuvant therapy and patients who had oxaliplatin stopped due to toxicity
• Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)
• Life expectancy of greater than 12 weeks
• Leukocytes >= 3,000/mcL
• Absolute neutrophil count >= 1,500/mcL
• Platelets >= 100,000/mcL
• Total bilirubin within normal institutional limits
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =< 2.5 X institutional upper limit of normal or =< 5 X institutional upper limit of normal for patients with known liver metastasis
• Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
• Women of child-bearing potential and men must agree to use adequate contraception (double barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and 4 months after completion of MK-2206 administration; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of MK-2206 administration
• Patients must be able to swallow whole tablets; nasogastric or gastrostomy (G) tube administration is not allowed; tablets must not be crushed or chewed
• Ability to understand and the willingness to sign a written informed consent document
• Tumor must be wild type for the KRAS and BRAF oncogenes, and must have known PIK3CA, AKT mutation status and PTEN expression status

Exclusion Criteria:

• Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study; if the patient has residual toxicity from prior treatment, toxicity must be =< grade 1 (or =< grade 2 for peripheral neuropathy and/or alopecia)
• Patients who are receiving or have received any other investigational agents within 30 days of study day 1

• Patient has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; however, patients with CNS metastases who have completed a course of therapy would be eligible for the study provided they are clinically stable for at least 1 month prior to entry as defined as:

  • No evidence of new or enlarging CNS metastasis
  • Off steroids that are used to minimize surrounding brain edema
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to MK-2206
• Patients receiving any medications or substances that are inhibitors or inducers of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP450 3A4) are ineligible
• Patients with diabetes or in risk for hyperglycemia should not be excluded from trials with MK-2206, but the hyperglycemia should be well controlled on oral agents before the patient enters the trial
• Cardiovascular baseline corrected QT by Fridericia's (QTcF) > 450 msec (male) or QTcF > 470 msec (female) will exclude patients from entry on study
• 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
• Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with MK-2206
• Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
• 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