Selinexor in Treating Patients With Abiraterone Acetate and/or Enzalutamide Refractory Metastatic Castration-Resistant Prostate Cancer
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02215161|
Recruitment Status : Terminated (Risk to benefit ratio is not acceptable)
First Posted : August 13, 2014
Results First Posted : June 26, 2018
Last Update Posted : June 26, 2018
|Condition or disease||Intervention/treatment||Phase|
|Castration Levels of Testosterone Hormone-Resistant Prostate Cancer Metastatic Prostate Carcinoma in the Soft Tissue Prostate Carcinoma Metastatic in the Bone PSA Progression Stage IV Prostate Adenocarcinoma AJCC v7||Drug: Selinexor||Phase 2|
I. To describe radiographic progression free survival (rPFS) associated with selinexor in patients with abiraterone (abiraterone acetate) refractory metastatic castration-resistant prostate cancer (mCRPC).
I. To measure prostate-specific antigen (PSA) changes at 12 weeks post-selinexor initiation.
II. To assess time to PSA progression. III. To measure time to development of >= 2 new bone lesions. IV. To compare the relationship of abiraterone-resistance status (primary vs acquired) and treatment outcome.
V. To determine the effect of selinexor on persistent pain associated with bone metastasis using the brief pain inventory (BPI) short form.
VI. To describe the safety profile of selinexor in patients with metastatic castration-resistant prostate cancer.
VII. To determine the effect of selinexor on circulating leukocyte exportin 1 (XPO-1) expression, leukocyte gene expression profile and macrophage inhibitory cytokine-1 (MIC-1) messenger ribonucleic acid (mRNA) expression.
VIII. To assess serum selinexor trough levels as a function of dose and time since last dose.
I. To describe the relationship of XPO-1 expression to PSA decline. II. To describe the expression profile of metastatic tumor and outcome. III. To describe the type of progression (e.g. pain, bone etc). IV. To define XPO-1 expression in patients for whom pre- and post-treatment biopsy is obtained.
Patients receive selinexor orally (PO) on days 1 and 3 of weeks 1-3. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 30 days and then every 6 months thereafter.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||14 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase II Single Agent Study of Selinexor (KPT-330) in Patients With Metastatic Castration-Resistant Prostate Cancer (mCRPC) and Prior Therapy With Abiraterone and/or Enzalutamide|
|Actual Study Start Date :||September 2, 2014|
|Actual Primary Completion Date :||February 15, 2017|
|Actual Study Completion Date :||April 2, 2018|
Experimental: Treatment (selinexor)
Patients receive selinexor PO on days 1 and 3 of weeks 1-3. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
- Radiographic Progression Free Survival (rPFS) [ Time Frame: From study start up to 3 years ]Defined as the time from study start until one of the following events occurs: >= 2 new bone lesions on technetium bone scan; Response Evaluation Criteria in Solid Tumors (RECIST)-defined tumor progression; clinical deterioration requiring a change in prostate cancer therapy, or at clinician discretion; surgery or radiation to treat a prostate cancer related indication; or death from any cause.
- Abiraterone Resistance Status (Primary Versus Acquired) [ Time Frame: At baseline ]Comparison of radiographic progression free survival between patients with primary abiraterone resistance and acquired abiraterone resistance using a Cox proportional hazards model.
- Time to PSA Progression [ Time Frame: Time between the first evaluation at which the response criteria are met and the first documentation of PSA progression or death or up to 3 years ]Time between the first evaluation at which the response criteria are met and the first documentation of PSA (Prostate-Specific Antigen) progression or death. Progression is defined as a rise in PSA of 50% above nadir value or 25% above baseline if there is no decline.
- Incidence of Non-serious Adverse Events [ Time Frame: Up to 3 years after treatment start ]Incidence of non-serious adverse events, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
- Comparison of Leukocyte Exportin 1 (XPO-1) and Macrophage Inhibitory Cytokine-1 (MIC-1) Gene Expression Levels Pre- and Post-Selinexor Treatment [ Time Frame: On days 1 and 15 of course 1 and on day 1 of courses 2 and 3 ]Total RNA isolated from leukocytes of patients will be used for quantitative polymerase chain reaction analysis (qPCR) in order to compare expression levels of XPO-1 and MIC-1 as a function of selinexor dose and total time on treatment.
- PSA Decline of ≥50% at 12 Weeks Post Therapy Initiation [ Time Frame: At 12 weeks post therapy initiation ]The number of patients experiencing a PSA decline from baseline of at least 50% in PSA at 12 weeks following the initiation of study therapy.
- Reduction in Pain for Symptomatic Patients, Measured Using the Brief Pain Inventory (BPI), Short Form [ Time Frame: At baseline and day 1 of every following cycle until end of treatment or 3 years after study start ]The effect of selinexor on persistent pain associated with bone metastasis, measured using the Brief Pain Inventory (BPI), Short Form. 0 denotes ''no pain'' and 10, ''pain as bad as you can imagine".
- Serum Selinexor Levels [ Time Frame: At day 1 of course 1, each treatment day until end of treatment up to 3 years ]Serum selinexor trough levels as a function of dose and time since last dose
- Time to Confirmed Development of >= 2 New Bone Lesions That Cannot be Attributable to Bone Scan Flare [ Time Frame: At week 8, 16, 24, and every 12 weeks thereafter up to 3 years after treatment start ]Defined as time interval between the date of treatment initiation and the date of documented new lesions. Evaluation criteria is defined by the PSAWG2 (Prostate-Specific Antigen Working Group 2) criteria for bone scan evaluation. The time will be 'backdated' to when the >= 2 new lesions were detected if a second scan is done to confirm progression.
- Incidence of Serious Adverse Events [ Time Frame: Up to 3 years after treatment start ]Incidence of serious adverse events, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
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): NCT02215161
|United States, California|
|University of California, San Francisco|
|San Francisco, California, United States, 94115|
|Principal Investigator:||Charles Ryan, MD||University of California, San Francisco|