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
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.
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
Drug: Akt Inhibitor MK2206
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
|Study Design:||Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 2 Study of MK-2206 in Previously Treated Metastatic Colorectal Cancer Patients Enriched for PTEN Loss and PIK3CA Mutation|
- Overall response rate (CR+PR) evaluated using Response Evaluation Criteria in Solid Tumors version 1.1 [ Time Frame: Up to 18 months ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: No ]Estimated using the Kaplan and Meier product limit method. Cox proportional hazards regression model will be used to identify prognostic factors for DR.
- OS [ Time Frame: Up to 18 months ] [ Designated as safety issue: No ]Estimated using the Kaplan and Meier product limit method. Cox proportional hazards regression model will be used to identify prognostic factors for OS.
- PFS [ Time Frame: From start of treatment to time of progression or death, whichever occurs first, assessed up to 18 months ] [ Designated as safety issue: No ]Estimated using the Kaplan and Meier product limit method. Cox proportional hazards regression model will be used to identify prognostic factors for PFS.
- Validation of the enrichment biomarker signature in metastatic sites [ Time Frame: Up to 18 months ] [ Designated as safety issue: No ]Samples will be analyzed using the Wilcoxon rank test. Chi-square or Fisher's exact test where appropriate will be used to determine whether high levels of marker expression correlate with PTEN status.
|Study Start Date:||March 2013|
|Estimated Primary Completion Date:||September 2015 (Final data collection date for primary outcome measure)|
Experimental: Treatment (Akt inhibitor MK2206)
Patients receive Akt inhibitor MK2206 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.
Drug: Akt Inhibitor MK2206
Other Names:Other: Laboratory Biomarker Analysis
Correlative studiesOther: Pharmacological Study
I. To determine the response rate to MK-2206 (Akt inhibitor MK2206), defined as complete response (CR) + partial response (PR).
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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01802320
|United States, Texas|
|M D Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Edmund S. Kopetz 713-792-2828 email@example.com|
|Principal Investigator: Edmund S. Kopetz|
|Principal Investigator:||Edmund Kopetz||M.D. Anderson Cancer Center|