Trametinib in Treating Patients With Progressive Metastatic Hormone-Resistant Prostate Cancer
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|ClinicalTrials.gov Identifier: NCT02881242|
Recruitment Status : Recruiting
First Posted : August 26, 2016
Last Update Posted : May 7, 2019
|Condition or disease||Intervention/treatment||Phase|
|Hormone-Resistant Prostate Cancer Metastatic Prostate Carcinoma Recurrent Prostate Carcinoma Stage IV Prostate Cancer||Other: Laboratory Biomarker Analysis Other: Quality-of-Life Assessment Drug: Trametinib||Phase 2|
PRIMARY OBJECTIVES I. To assess the activity of trametinib in metastatic castration resistant prostate cancer (mCRPC) that has progressed on either enzalutamide or abiraterone acetate.
SECONDARY OBJECTIVES I. Durability of prostate specific antigen (PSA) response as measured by the time to PSA progression as defined by Prostate Cancer Working Group 2 guidelines for PSA progression.
II. Maximal PSA response. III. Quality of life by Functional Assessment of Cancer Therapy- Prostate (FACT-P).
IV. Time to initiation of alternative antineoplastic therapy. V. Time to radiographic progression. VI. Objective response rate according to Response Evaluation Criteria in Solid Tumors (RECIST) guidelines.
VII. Overall survival measured as time from enrollment until death. VIII. Safety and tolerability. IX. Analysis of trametinib target engagement of mitogen-activated extracellular signal-related kinase (MEK1/2) is assessed by presence of p-ERK, the primary phosphorylation target of activated MEK1/2, in pre-treatment and at progression radiographically directed metastatic tumor biopsies by immunohistochemistry evaluation of p-ERK. Markers of cell proliferation (Ki67) and apoptosis (p27) will also be assessed.
XI. Investigation of molecular correlates to resistance and sensitivity to trametinib using pre-treatment and at progression metastatic biopsies.
XII. Discovery of one or a set of possible discriminative networks that are associated with a response to trametinib.
XII. Enrichment for patients in the second phase who have tumors exhibiting genomic features associated with a response to trametinib.
XIV. Analyses of circulating tumor deoxyribonucleic acid (ctDNA) for genomic aberrations correlated to treatment response.
Patients receive trametinib orally (PO) once daily (QD). Treatment continues in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 2 and 4 weeks, and then every 4 weeks thereafter.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||62 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Single-Arm, Open-Label, Two-Stage Phase II Study of the MEK 1/2 Inhibitor Trametinib in Men With Progressive Metastatic Castrate Resistant Prostate Cancer|
|Actual Study Start Date :||January 30, 2018|
|Estimated Primary Completion Date :||January 31, 2020|
|Estimated Study Completion Date :||January 31, 2021|
Experimental: Treatment (trametinib)
Patients receive trametinib PO QD. Treatment continues in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Other: Quality-of-Life Assessment
Other Name: Quality of Life Assessment
- PSA response rate [ Time Frame: At 12 weeks ]
- Response rate assessed by RECIST criteria [ Time Frame: Up to 24 weeks ]Will be defined as decline in PSA of 30% or more, any decline of PSA of 50% or more, partial or complete response at 12 weeks, and freedom from radiographic progression at 24 weeks.
- Change in markers of cell proliferation (Ki67) and apoptosis (p27), assessed by immunohistochemistry [ Time Frame: Baseline up to 24 weeks ]Mixed effects logistic regression models to assess changes in markers over time, correlations between markers over time and associations between markers and treatment response (conditional logistic regression) will be used.
- Change in trametinib target engagement of MEK1/2 defined by the presence of p-ERK, assessed by immunohistochemistry [ Time Frame: Baseline up to 24 weeks ]Mixed effects logistic regression models to assess changes in markers over time, correlations between markers over time and associations between markers and treatment response (conditional logistic regression) will be used.
- Durability of PSA response as measured by time to PSA progression as defined by PCWG2 guidelines [ Time Frame: Up to 30 months ]
- Incidence of adverse events, graded according to the Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 30 months ]
- Maximal PSA response [ Time Frame: Up to 30 months ]
- Molecular correlates defined by gene expression, assessed using ribonucleic acid-sequencing, and mutational events, assessed using DNA exome-seq [ Time Frame: Up to 24 weeks ]Statistical bootstrap and Pearsons Correlation will be used to determine the relationship of phenotype to mutations and clinical variables. Fisher exact tests and logistic regression models will be used to evaluate the relationships between specific variations and treatment response.
- Objective radiographic response rate according to RECIST guidelines [ Time Frame: Up to 24 weeks ]
- Overall survival [ Time Frame: Time from enrollment until death, assessed for up to 30 months ]
- Quality of life, assessed by FACT-P [ Time Frame: Up to 30 months ]
- Time to initiation of alternative anti-neoplastic therapy [ Time Frame: Up to 30 months ]
- Time to radiographic progression [ Time Frame: Up to 24 weeks ]
- ctDNA genomic aberrations, assessed by exome sequencing [ Time Frame: Up to 24 weeks ]
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): NCT02881242
|United States, California|
|UCLA / Jonsson Comprehensive Cancer Center||Recruiting|
|Los Angeles, California, United States, 90095|
|Contact: Matthew B. Rettig 310-794-3565 firstname.lastname@example.org|
|Principal Investigator: Matthew B. Rettig|
|Principal Investigator:||Matthew Rettig||UCLA / Jonsson Comprehensive Cancer Center|