Clinical Trial: 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

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: A Phase 2 Study of MK-2206 in Previously Treated Metastatic Colorectal Cancer Patients Enriched for PTEN Loss and PIK3CA Mutation

Brief 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.

Detailed Summary:

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.


Sponsor: National Cancer Institute (NCI)

Current Primary Outcome: Overall response rate (CR+PR) evaluated using Response Evaluation Criteria in Solid Tumors version 1.1 [ Time Frame: Up to 18 months ]

Original Primary Outcome: Overall response rate (CR+PR) evaluated using RECIST version 1.1 [ Time Frame: Up to 18 months ]

Current Secondary Outcome:

  • 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 ]
    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 ]
    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 ]
    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 ]
    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.


Original Secondary Outcome:

  • Validation of the enrichment biomarker signature in metastatic sites [ Time Frame: Up to 18 months ]
    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.
  • PFS [ Time Frame: From start of treatment to time of progression or death, whichever occurs first, assessed up to 18 months ]
    Estimated using the Kaplan and Meier product limit method. Cox proportional hazards regression model will be used to identify prognostic factors for PFS.
  • OS [ Time Frame: Up to 18 months ]
    Estimated using the Kaplan and Meier product limit method. Cox proportional hazards regression model will be used to identify prognostic factors for OS.
  • 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 ]
    Estimated using the Kaplan and Meier product limit method. Cox proportional hazards regression model will be used to identify prognostic factors for DR.


Information By: National Cancer Institute (NCI)

Dates:
Date Received: February 27, 2013
Date Started: March 2013
Date Completion:
Last Updated: December 13, 2016
Last Verified: December 2016