Clinical Trial: Selumetinib in Treating Patients With Biliary Cancer That Cannot Be Removed By Surgery

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase 2 Study of AZD6244 in Biliary Cancers

Brief Summary: This phase II trial is studying how well selumetinib works in treating patients with biliary cancer that cannot be removed by surgery. Selumetinib 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] and partial response [PR]) in patients with unresectable biliary carcinoma treated with AZD6244 (selumetinib).

SECONDARY OBJECTIVES:

I. To evaluate the toxicity profile of this drug in these patients. II. To evaluate the 6- and 12-month survival, 6-month progression-free survival, and overall survival rates of patients treated with this drug.

III. To correlate genetic mutations, epigenetic silencing, and/or protein levels of RAS/RAF/MEK/ERK signaling pathway activation with therapeutic efficacy of AZD6244 in these patients.

IV. To genotype tumors for the presence of RAS mutations (i.e., NRAS, KRAS, HRAS) and BRAF mutations (e.g., V600E) in biliary tumor samples from these patients.

V. To assess the presence of activation of the MEK1, MEK2, ERK, and/or Akt pathways in tumor samples from these patients.

VI. To assess the epigenetic alterations (i.e., methylation) affecting the level of gene/protein expression of RASSF1A, NORE1A, and NORE1B in tumor samples from these patients.

OUTLINE:

Patients receive oral selumetinib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Formalin fixed paraffin-embedded tissue blocks or fresh tissue samples are obtained from all patients prior to treatment. Tissue samples are analyzed by immunohistochemistry for the expression level of target protei
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome: Objective Response Rate (CR and PR) [ Time Frame: Every 8 weeks ]

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR


Original Primary Outcome: Objective response rate (complete and partial response) as measured by RECIST

Current Secondary Outcome:

  • Toxicity Profile of AZD6244 [ Time Frame: From the time of first treatment with AZD6244, assessed up to 4 weeks ]
    Toxicitity will be assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v 3.0
  • Median Progression Free Survival for Patients [ Time Frame: Up to 6 months ]
    Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
  • Overall Survival [ Time Frame: Up to 12 months ]
  • RAS/RAF/MEK/ERK Signaling Pathway Activation [ Time Frame: At baseline ]
  • Protein Levels of RAS/RAF/MEK/ERK Signaling Pathway Activation [ Time Frame: At baseline ]
    Measure the proteins levels of RAS/RAF/MEK/ERK signaling pathway activation to AZD6244


Original Secondary Outcome:

  • Toxicity profile of AZD6244 as assessed by NCI CTCAE v3.0
  • Progression-free survival
  • Overall Survival
  • RAS/RAF/MEK/ERK Signaling Pathway Activation
  • Genetic mutations
  • Epigenetic silencing
  • Protein Levels of RAS/RAF/MEK/ERK Signaling Pathway Activation


Information By: National Cancer Institute (NCI)

Dates:
Date Received: November 2, 2007
Date Started: November 2007
Date Completion:
Last Updated: March 22, 2016
Last Verified: March 2016