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
|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||Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (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 (RECIST) Version 1.1 [ Time Frame: Up to 18 months ]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.
- Duration of Tumor Response (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.
- Overall Survival (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.
- Progression-free Survival (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.
|Actual Study Start Date:||March 2013|
|Estimated Study Completion Date:||December 2017|
|Primary Completion Date:||June 2015 (Final data collection date for primary outcome measure)|
Experimental: Treatment (Akt inhibitor MK2206)
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.
Drug: Akt Inhibitor MK2206
Other Name: MK2206Other: 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|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Edmund Kopetz||M.D. Anderson Cancer Center|