Akt Inhibitor MK2206 in Treating Patients With Advanced Breast Cancer
Male Breast Cancer
Recurrent Breast Cancer
Stage IIIB Breast Cancer
Stage IIIC Breast Cancer
Stage IV Breast 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:||Phase II Trial of AKT Inhibitor MK2206 in Patients With Advanced Breast Cancer Who Have Tumors With a PIK3CA Mutation, or an AKT Mutation, and/or PTEN Loss/PTEN Mutation|
- Number of Participants With Response Defined Using Response Evaluation Criteria In Solid Tumors (RECIST) [ Time Frame: Up to 3 weeks after completion of study treatment, for up to 1 year ] [ Designated as safety issue: No ]Number of participants with response defined by RECIST version 1.1: Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: appearance of one or more new lesions is also considered progressions). Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
- Number of Participants With Objective Response [ Time Frame: 4 weeks following beginning treatment, repeat confirmation 4-6 weeks following response, up to 1 year ] [ Designated as safety issue: No ]Only those participants who have measurable disease present at baseline, have received at least four doses of MK2206, and have had their disease re-evaluated will be considered evaluable for response. Response classified according the RECIST definitions, and re-evaluated for response every 12 weeks. (Note: Participants who exhibit objective disease progression prior to receiving four doses of therapy will also be considered evaluable.) In addition to a baseline scan, confirmatory scans should also be obtained 4-6 weeks following initial documentation of objective response, and then revert to scheduled repeat imaging.
- 6 Month Progression-free Survival (PFS) [ Time Frame: From start of treatment to time of progression or death or six months whichever occurs first, assessed at 6 months ] [ Designated as safety issue: No ]Number of participants progression free at 6 months. PFS is defined as the duration of time from start of treatment, or time of progression or death, whichever occurs first. The PFS for this outcome was assessed at 6 months post treatment.
- Median Response Duration [ Time Frame: Response assessment 4 weeks from beginning of treatment, response recorded from the start of treatment until disease progression/recurrence, up to 1 year ] [ Designated as safety issue: No ]
The duration of the response is from the time response is achieved until disease progression is detected. The duration of overall response is measured 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 (taking as reference for progressive disease the smallest measurements recorded since the treatment started). The duration of overall CR is measured from the time measurement criteria are first met for CR until the first date that progressive disease is objectively documented.
Response re-evaluated every 12 weeks. In addition to a baseline scan, confirmatory scans should also be obtained 4-6 weeks following initial documentation of objective response.
- Cell Proliferation as Measured by the Change in Percent Ki-67 Positive Cells [ Time Frame: Baseline to 2 weeks ] [ Designated as safety issue: No ]Ki-67 will be scored as % positive cells to determine whether there is a change % Ki-67+ cells before treatment versus after 2 weeks of treatment.
- Apoptosis Assessed by Cleaved Caspase-3 [ Time Frame: Up to 30 days after completion of study treatment, up to 1 year ] [ Designated as safety issue: No ]Assessment of apoptosis by immunohistochemistry to active caspase-3.
|Study Start Date:||March 2011|
|Primary Completion Date:||August 2014 (Final data collection date for primary outcome measure)|
Experimental: Treatment (Akt inhibitor MK-2206)
Akt Inhibitor MK-2206 mg orally once a week on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: Akt inhibitor MK2206
Given orally (PO) weekly, starting (dose 0) at 200 mg
Other Name: MK2206Other: laboratory biomarker analysis
Correlative studiesOther: pharmacological study
Other Name: pharmacological studies
I. To determine whether v-akt murine thymoma viral oncogene (Akt) inhibitor MK2206 achieves objective tumor responses (complete response [CR], partial response [PR]) in advanced breast cancer patients who have a phosphoinositide-3-kinase, catalytic, alpha polypeptide (PIK3CA) or Akt mutation and/or phosphatase and tensin homolog (PTEN) loss or mutation.
I. To determine the 6 month progression-free survival on MK2206. II. To determine baseline molecular markers that may predict clinical outcome. III. To determine pharmacodynamic markers in blood and tumor tissue that may predict a decrease in Ki-67 and clinical outcome.
IV. To determine safety and tolerability of MK2206 in previously treated patients with advanced breast cancer.
V. To determine if decrease in Ki-67 at 2 weeks correlates with anti-tumor effect (CR, PR, or stable disease [SD] > 6 months).
VI. To determine concordance of PIK3CA and PTEN status between primary tumor and distant metastasis.
VII. To determine concordance of PIK3CA status of circulating free deoxyribonucleic acid (DNA) and distant metastasis.
Patients receive Akt Inhibitor MK-2206 orally (PO) on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 3 weeks.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01277757
|United States, Massachusetts|
|Dana-Farber Cancer Institute|
|Boston, Massachusetts, United States, 02115|
|Beth Israel Deaconess Medical Center|
|Boston, Massachusetts, United States, 02215|
|United States, New York|
|Columbia University Medical Center|
|New York, New York, United States, 10032|
|United States, Tennessee|
|Vanderbilt-Ingram Cancer Center|
|Nashville, Tennessee, United States, 37232|
|United States, Texas|
|M D Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Funda Meric-Bernstam||M.D. Anderson Cancer Center|