Selumetinib in Treating Patients With Recurrent or Persistent Endometrial Cancer
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|ClinicalTrials.gov Identifier: NCT01011933|
Recruitment Status : Completed
First Posted : November 11, 2009
Results First Posted : January 20, 2014
Last Update Posted : July 23, 2019
|Condition or disease||Intervention/treatment||Phase|
|Endometrial Adenocarcinoma Endometrial Adenosquamous Carcinoma Endometrial Clear Cell Adenocarcinoma Recurrent Uterine Corpus Carcinoma||Other: Diagnostic Laboratory Biomarker Analysis Drug: Selumetinib||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||54 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Evaluation of AZD6244 (NSC #748727) in the Treatment of Recurrent or Persistent Endometrial Carcinoma|
|Study Start Date :||September 2009|
|Actual Primary Completion Date :||January 2016|
|Actual Study Completion Date :||January 2016|
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
- 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.
- Participants With Severity of Adverse Effects as Assessed by CTCAE v3.0 [ Time Frame: Each cycle during treatment and 30 days after the last treatment. ]
- Duration of Progression-free Survival [ Time Frame: Every other cycle for the first 6 months; then every 3 months thereafter for up to 5 years ]Progression is defined according to RECIST v1.0 as at least a 20% increase in the sum of LD target lesions taking as reference the smallest sum LD recorded since study entry, the appearance of one or more new lesions, death due to disease without prior objective documentation of progression, global deterioration in health status attributable to the disease requiring a change in therapy without objective evidence of progression, or unequivocal progression of existing non-target lesions.
- Duration of Overall Survival [ Time Frame: Every cycle during treatment, then every 3 months for the first 2 years, then every six months for the next three years and then annually for the next 5 years. ]Overall survival is defined as the duration of time from study entry to time of death or the date of last contact.
- Number of Participants Off Study Therapy for Each Reason Specified. [ Time Frame: from study entry until end of study treatment, up to 5 years. ]
- Patient Vital Status [ Time Frame: Study entry up to 2 years ]Patients alive or dead after 24 months from time of study entry.
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): NCT01011933
|Principal Investigator:||Robert Coleman||NRG Oncology|