Selumetinib in Treating Patients With Recurrent or Persistent Endometrial Cancer
Endometrial Adenosquamous Carcinoma
Endometrial Clear Cell Adenocarcinoma
Recurrent Uterine Corpus Carcinoma
Other: Diagnostic Laboratory Biomarker Analysis
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Evaluation of AZD6244 (NSC #748727) in the Treatment of Recurrent or Persistent Endometrial Carcinoma|
- 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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]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 Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
- Duration of Progression-free Survival [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
- Duration of Overall Survival [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
- Reason Off Study Therapy [ Time Frame: from study entry until end of study treatment ] [ Designated as safety issue: No ]
- Patient Vital Status [ Time Frame: Study entry up to 2 years ] [ Designated as safety issue: No ]Patients alive or dead after 24 months from time of study entry.
|Study Start Date:||September 2009|
|Study Completion Date:||January 2016|
|Primary Completion Date:||January 2016 (Final data collection date for primary outcome measure)|
Experimental: Treatment (selumetinib)
Patients receive selumetinib PO twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Blood and archived tumor tissue samples are collected for biomarker studies.
Other: Diagnostic Laboratory Biomarker Analysis
Correlative studiesDrug: Selumetinib
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.
I. To determine the duration of progression-free survival and overall survival.
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, EGFR, pEGFR, EGF, PELP1 and MTA1s.
OUTLINE: This is a multicenter study.
Patients receive selumetinib orally (PO) twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Blood and archived tumor tissue samples are collected for biomarker studies.
After completion of study therapy, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01011933
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|Principal Investigator:||Robert Coleman||NRG Oncology|