Selumetinib and Akt Inhibitor MK-2206 in Treating Patients With Refractory or Advanced Gallbladder or Bile Duct Cancer That Cannot Be Removed By Surgery
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|ClinicalTrials.gov Identifier: NCT01859182|
Recruitment Status : Withdrawn
First Posted : May 21, 2013
Last Update Posted : September 9, 2014
|Condition or disease||Intervention/treatment||Phase|
|Adenocarcinoma of the Gallbladder Adenocarcinoma With Squamous Metaplasia of the Gallbladder Adult Primary Cholangiocellular Carcinoma Advanced Adult Primary Liver Cancer Cholangiocarcinoma of the Extrahepatic Bile Duct Localized Unresectable Adult Primary Liver Cancer 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||Drug: selumetinib Drug: Akt inhibitor MK2206 Other: laboratory biomarker analysis Other: pharmacogenomic studies Procedure: quality-of-life assessment||Phase 2|
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).
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.
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 Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||0 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Multicenter Phase II Study of the Combination of AZD6244 Hydrogen Sulfate and MK-2206 in Patients With Refractory Advanced Biliary Cancers|
|Study Start Date :||January 2013|
|Actual Primary Completion Date :||May 2013|
|Actual Study Completion Date :||May 2013|
Experimental: Treatment (selumetinib, Akt inhibitor MK2206)
Patients receive Akt inhibitor MK-2206 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.
Drug: Akt inhibitor MK2206
Other: laboratory biomarker analysis
Other: pharmacogenomic studies
Procedure: quality-of-life assessment
- 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.
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01859182
|Principal Investigator:||Tanios Bekaii-Saab||Ohio State University|