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.
PRIMARY OBJECTIVES: I. To determine the response rate to MK-2206 (Akt inhibitor MK2206), defined as complete response (CR) + partial response (PR). SECONDARY OBJECTIVES: I. To determine response rate to MK-2206 in patients with phosphatase and tensin homolog (PTEN) loss or phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) mutation in a pretreatment biopsy from a metastatic site. II. To determine progression-free survival (PFS) and overall survival (OS). III. To determine the time to treatment failure (TTF), and duration of tumor response (DR). IV. To determine the safety profile and tolerability of this regimen in this patient population. V. To determine effect of PTEN, v-raf murine sarcoma viral oncogene homolog B1 (BRAF), PIK3CA, and AKT mutations and semi-quantitative grading of PTEN expression on clinical response. OUTLINE: Patients receive Akt inhibitor MK2206 orally (PO) on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 24 months in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 6 months.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
18
Given PO
Correlative studies
Correlative studies
M D Anderson Cancer Center
Houston, Texas, United States
Overall Response Rate (CR+PR) Evaluated Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Complete Response (CR): Disappearance all target lesions. Any pathological lymph nodes must have reduction in short axis to \<10 mm. Partial Response (PR): \> 30% decrease in sum diameters of target lesions, reference baseline sum diameters. Progressive Disease (PD): \> 20% increase in sum diameters of target lesions, reference smallest sum on study (includes baseline sum if smallest on study). In addition to relative increase of 20%, sum must demonstrate absolute increase of \>5 mm. (Note: appearance of 1/\> new lesions also considered progressions). Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, reference smallest sum diameters while on study.
Time frame: Up to 18 months
Duration of Tumor Response (DR)
Estimated using the Kaplan and Meier product limit method. Cox proportional hazards regression model will be used to identify prognostic factors for DR.
Time frame: From the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 18 months
Overall Survival (OS)
Estimated using the Kaplan and Meier product limit method. Cox proportional hazards regression model will be used to identify prognostic factors for OS.
Time frame: Up to 18 months
Progression-free Survival (PFS)
Estimated using the Kaplan and Meier product limit method. Cox proportional hazards regression model will be used to identify prognostic factors for PFS.
Time frame: From start of treatment to time of progression or death, whichever occurs first, assessed up to 18 months
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.