Clinical Trial: Selumetinib in Treating Patients With Recurrent or Persistent Endometrial Cancer

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

Official Title: A Phase II Evaluation of AZD6244 (NSC #748727) in the Treatment of Recurrent or Persistent Endometrial Carcinoma

Brief Summary: This phase II trial is studying how well selumetinib works in treating patients with recurrent or persistent endometrial cancer that has come back or is persistent. Selumetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To assess the activity of AZD6244 (selumetinib) for patients with recurrent or persistent endometrial cancer with the frequency of patients who survive progression-free for at least 6 months after initiating therapy or have objective tumor response.

II. To determine the nature and degree of toxicity of AZD6244 as assessed by CTCAE v3.0 in this cohort of patients.

SECONDARY OBJECTIVE:

I. To determine the duration of progression-free survival and overall survival.

EXPLORATORY OBJECTIVES:

I. To explore the associations between select biomarkers and response to AZD6244 (progression-free survival status >6 months and objective tumor response), measures of clinical outcome (progression-free survival and overall survival) or disease status including histologic cell type.

II. Mutations and single nucleotide polymorphisms in BRAF, KRAS2, FGFR2, PI3KCA, AKT1, AKT2, AKT3 and PTEN in DNA from formalin-fixed and paraffin-embedded (FFPE) tumor and/or normal blood cells.

III. Immunohistochemical expression of ERK, pERK, GSK3betta, pGSK3betta, PR-A, PR-B, pPR, ER-alpha, ER-beta, BRAF, KRAS, PTEN, EGFR, pEGFR, EGF, PELP1 and MTA1s in FFPE tumor.

IV. To explore the relationship among the panel of biomarkers evaluated in this cohort including mutations and single nucleotide polymorphisms in BRAF, KRAS2, FGFR2, PI3KCA, AKT1, AKT2, AKT3 and PTEN as well as immunohistochemical expression of ERK, pERK, GSK3betta, pGSK3betta, PR-A, PR-B, pPR, ER-alpha, ER-beta, BRAF, KRAS, PTEN
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome:

  • Number of Participants With or Without Progression-free Survival for > 6 Months by Response Evaluation Criteria for Solid Tumors (RECIST) [ Time Frame: > 6 months from study entry ]

    Number of participants who survived progression-free for more than 6 months.

    Progression is defined using Response Evaluation Criteria for Solid Tumors (RECIST), as a 20% increase in the sum of the longest diameter of target lesions, or the appearance of one or more new lesions, or unequivocal progression of existing non-target lesions in the opinion of the treating physician, or global deterioration in health status attributable to the disease requiring a change in therapy without objective evidence of progression.

  • Objective Tumor Response Rate Assessed by RECIST [ Time Frame: From study entry, assessed up to 5 years ]
    Per Response Evaluation Criteria In Solid Tumors (RECIST) Criteria: Complete Response (CR) is disappearance of all target and non-target lesions and no evidence of new lesions documented by two disease assessments at least 4 weeks apart. Normalization of CA125, if elevated at study entry, is required; Partial Response (PR) is at least a 30% decrease in the sum of longest dimensions (LD) of all target measurable lesions taking as reference the baseline sum of LD; Increasing Disease is at least a 20% increase in the sum of LD of target lesions taking as references the smallest sum LD or the appearance of new lesions within 8 weeks of study entry; Stable Disease is any condition not meeting the above criteria.
  • Frequency and Severity of Adverse Effects as Assessed by CTCAE v3.0 [ Time 

    Original Primary Outcome:

    • Progression-free survival rate for ≥ 6 months or objective tumor response rate
    • Frequency and severity of adverse effects as assessed by NCI CTCAE v3.0


    Current Secondary Outcome:

    • Duration of Progression-free Survival [ Time Frame: Up to 5 years ]
    • Duration of Overall Survival [ Time Frame: Up to 5 years ]


    Original Secondary Outcome: Duration of progression-free survival and overall survival

    Information By: National Cancer Institute (NCI)

    Dates:
    Date Received: November 10, 2009
    Date Started: September 2009
    Date Completion:
    Last Updated: April 15, 2016
    Last Verified: April 2016