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

Inclusion Criteria:

* Patients must have histologically confirmed, radiologically measurable metastatic or locally advanced unresectable colorectal adenocarcinoma that is amenable to image-guided biopsy; disease in previously radiated regions may not be considered measurable unless there has been demonstrated progression in the lesion
* Patients must have progressed on or been intolerant to a fluoropyrimidine-based chemotherapy regimen; there is no limit on the number of prior treatment regimens permitted
* 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 =\< institution upper limit of normal
* 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 =\< institution upper limit of normal 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 v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (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, or who have previously received MK-2206 at any time
* 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