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
Condition: Colon Mucinous Adenocarcinoma; Colon Signet Ring Cell Adenocarcinoma; Rectal Mucinous Adenocarcinoma; Rectal Signet Ring Cell Adenocarcinoma; Recurrent Colon Carcinoma; Recurrent Rectal Carcinoma; Stage IIIA Colon Cancer; Stage IIIA Rectal Cancer; Stage IIIB Colon Cancer; Stage IIIB Rectal Cancer; Stage IIIC Colon Cancer; Stage IIIC Rectal Cancer; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer
MeSH terms: Carcinoma; Adenocarcinoma; Rectal Neoplasms; Colonic Neoplasms; Adenocarcinoma, Mucinous; Cystadenocarcinoma; Carcinoma, Signet Ring Cell; Recurrence
Intervention: Akt Inhibitor MK2206; Laboratory Biomarker Analysis; Pharmacological Study
Intervention description: Given PO; Correlative studies; Correlative studies
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 18.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well v-akt murine thymoma viral oncogene homolog 1 (Akt)
      inhibitor MK2206 works in treating patients with previously treated colon or rectal cancer
      that has spread from the primary site to other places in the body or nearby tissue or lymph
      nodes and cannot be removed by surgery. 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 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