Clinical Trial: Selumetinib and Akt Inhibitor MK-2206 in Treating Patients With Refractory or Advanced Gallbladder or Bile Duct Cancer That Cannot Be Removed By Surgery

Study Status: Withdrawn
Recruit Status: Withdrawn
Study Type: Interventional

Official Title: A Multicenter Phase II Study of the Combination of AZD6244 Hydrogen Sulfate and MK-2206 in Patients With Refractory Advanced Biliary Cancers

Brief Summary: This phase II trial studies how well selumetinib and Akt inhibitor MK-2206 work in treating patients with refractory or advanced gallbladder or bile duct cancer that cannot be removed by surgery. Selumetinib and Akt inhibitor MK-2206 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To evaluate the objective response rate (complete response [CR] + partial response [PR]), as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria, in patients with refractory advanced biliary cancers receiving the combination of AZD6244 hydrogen sulfate (selumetinib) and MK-2206 (Akt inhibitor MK-2206).

SECONDARY OBJECTIVES:

I. To determine the overall and progression-free survival in patients with refractory advanced biliary cancer receiving MK-2206 and AZD6244 hydrogen sulfate.

II. To determine the frequency and severity of adverse events and tolerability of AZD6244 hydrogen sulfate + MK-2206 in patients with advanced refractory biliary cancer receiving this regimen.

III. To evaluate the effects of AZD6244 hydrogen sulfate plus MK-2206 on the inflammatory cytokine and immune cell profiles as well as on cancer cachexia.

IV. To determine the presence of genetic mutations of phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt) and mitogen-activated protein kinase (MAPK) signaling pathway genes (other than v-raf murine sarcoma viral oncogene homolog [BRAF] V600E) relevant to biliary cancer and how these correlate with and may predict objective response to treatment with AZD6244 hydrogen sulfate and MK-2206.

V. To assess and validate target inhibition in patients with refractory advanced biliary cancer receiving the combination of MK-2206 plus AZD6244 hydrogen sulfate.

VI. To determine the pharmacogenetic profile as a way of assessing inter-individual variability as well as
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome: Proportion of patients who have a response (PR or CR), assessed by the RECIST v1.1 [ Time Frame: 6 months ]

Calculated with corresponding 95% binomial confidence intervals.


Original Primary Outcome: Proportion of patients who have a response (PR or CR), assessed by the RECIST v1.1 [ Time Frame: Up to 6 months ]

Calculated with corresponding 95% binomial confidence intervals.


Current Secondary Outcome:

  • Frequency and severity of adverse events as per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0 [ Time Frame: Up to 4 weeks ]
    Frequency and severity of adverse events and tolerability of the regimen in each of the patient groups will be collected and summarized by descriptive statistics.
  • Changes in QOL evaluated using the Functional Assessment of Cancer Therapy - General (FACT-G) [ Time Frame: Baseline to 8 weeks ]
    Changes in overall quality of life will be explored in relation to severe toxicity incidence and in particular to incidence of cachexia. Graphical analyses will be used to assess patterns in these patient reported outcomes in relation to the clinical and tolerability outcomes of incidence.


Original Secondary Outcome:

  • Frequency and severity of adverse events as per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0 [ Time Frame: Up to 6 months ]
    Collected and summarized by descriptive statistics.
  • Overall survival [ Time Frame: From the date of study registration to the death, assessed up to 6 months ]
    Kaplan-Meier curves will be used.
  • Progression-free survival (PFS) [ Time Frame: Time from start of treatment to time of documented progression or death whichever occurs first, assessed up to 6 months ]
    Kaplan-Meier curves will be used. Exact binomial 95% confidence intervals for the PFS-based proportions will be calculated.
  • Changes in QOL evaluated using the Functional Assessment of Cancer Therapy - General (FACT-G) [ Time Frame: Baseline to 8 weeks ]
    Changes in overall quality of life will be explored in relation to severe toxicity incidence and in particular to incidence of cachexia. Graphical analyses will be used to assess patterns in these patient reported outcomes in relation to the clinical and tolerability outcomes of incidence.


Information By: National Cancer Institute (NCI)

Dates:
Date Received: May 17, 2013
Date Started: January 2013
Date Completion:
Last Updated: September 8, 2014
Last Verified: October 2013