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

Advanced Adult Primary Liver Cancer Clinical Trial

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

Status Withdrawn

Clinical Trial 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.

Clinical Trial Description

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 how these relate to clinical outcomes.

VII. To determine genetic variants and mutations in genes encoding drug metabolizing enzymes and transporters, and genes involved in tumor biology, and how these may be related to response to treatment.

VIII. To evaluate the effect of combined MAPK and PI3K/Akt inhibition on skeletal muscle anabolism in patients receiving treatment with AZD6244 hydrogen sulfate and MK-2206.

IX. To conduct quality of life analyses in patients receiving the combination of AZD6244 hydrogen sulfate plus MK-2206.

OUTLINE:

Patients receive Akt inhibitor MK-2206 orally (PO) on days 1, 8, 15, and 22 (days 8, 15, and 22 of course 1) and selumetinib 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 4 weeks. ;

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma of the Gallbladder
• Adenocarcinoma With Squamous Metaplasia of the Gallbladder
• Adult Primary Cholangiocellular Carcinoma
• Advanced Adult Primary Liver Cancer
• Bile Duct Neoplasms
• Cholangiocarcinoma
• Cholangiocarcinoma of the Extrahepatic Bile Duct
• Gallbladder Neoplasms
• Liver Neoplasms
• Localized Unresectable Adult Primary Liver Cancer
• Metaplasia
• Metastatic Extrahepatic Bile Duct Cancer
• Recurrent Adult Primary Liver Cancer
• Recurrent Extrahepatic Bile Duct Cancer
• Stage II Gallbladder Cancer
• Stage IIIA Gallbladder Cancer
• Stage IIIB Gallbladder Cancer
• Stage IVA Gallbladder Cancer
• Stage IVB Gallbladder Cancer
• Unresectable Extrahepatic Bile Duct Cancer

• NCT number: NCT01859182
• Study type: Interventional
• Source: National Cancer Institute (NCI)
• Status: Withdrawn
• Phase: Phase 2
• Start date: January 2013
• Completion date: May 2013