Trial record 5 of 101 for:    mdv3100 | Open Studies

Molecular Features and Pathways in Predicting Drug Resistance in Patients With Metastatic Hormone-Resistant Prostate Cancer Receiving Enzalutamide

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2016 by OHSU Knight Cancer Institute
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier:
NCT02228265
First received: August 25, 2014
Last updated: April 20, 2016
Last verified: April 2016
  Purpose
This research trial studies molecular features and pathways in predicting drug resistance in patients with hormone-resistant prostate cancer that has spread to other parts of the body and who are receiving enzalutamide. Studying samples of blood and tissue in the laboratory from patients receiving enzalutamide may help doctors learn more about molecular features and pathways that may cause prostate cancer to be resistant to the drug.

Condition Intervention
Hormone-Resistant Prostate Cancer
Prostate Adenocarcinoma
Recurrent Prostate Carcinoma
Stage IV Prostate Cancer
Other: Cytology Specimen Collection Procedure
Drug: Enzalutamide
Other: Laboratory Biomarker Analysis

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Identifying Mechanisms of Resistance to Enzalutamide (MDV3100) Treatment in Men With Castration-Resistant Prostate Cancer

Resource links provided by NLM:


Further study details as provided by OHSU Knight Cancer Institute:

Primary Outcome Measures:
  • PSA response, a binary variable indicating whether the PSA level has declined >= 50% within 12 weeks of beginning enzalutamide treatment [ Time Frame: Within 12 weeks ] [ Designated as safety issue: No ]
    Will be reported with 95% exact confidence interval.


Secondary Outcome Measures:
  • Degree of PSA decline [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    Simple linear regression will be used to assess the association between molecular biomarker predictors and the continuous endpoints. Logarithm transformation or other forms of transformation may be conducted to the continuous endpoints to address the skewedness of the distributions if necessary.

  • Disease-specific survival [ Time Frame: Time from day 1 of the study drug to date of death from prostate cancer, assessed up to 4 years ] [ Designated as safety issue: No ]
    Will be graphically illustrated using Kaplan-Meier plots of estimated survival distribution for patients (</>= 50%) PSA decline at 12 weeks. Log-rank test will be fitted to determine whether the estimated survival distribution of each time-to-event endpoint differs for patients with PSA decline >= 50% vs. patients with PSA decline < 50%. Cox regression models will be fitted to obtain the estimated hazard ratio for each time-to-event endpoints for patients who had >= 50% PSA decline at 12 weeks vs. those who had not.

  • Maximal PSA decline observed while on study [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
    Simple linear regression will be used to assess the association between molecular biomarker predictors and the continuous endpoints. Logarithm transformation or other forms of transformation may be conducted to the continuous endpoints to address the skewedness of the distributions if necessary.

  • Objective response [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
    Will be summarized using the estimated proportion and 95% confidence interval. Simple logistic regression model will be used to assess the association between molecular biomarker predictors and these binary secondary endpoints.

  • Overall survival [ Time Frame: Time from day 1 of study drug treatment to date of death from any cause, assessed up to 4 years ] [ Designated as safety issue: No ]
    Will be graphically illustrated using Kaplan-Meier plots of estimated survival distribution for patients (</>= 50%) PSA decline at 12 weeks. Log-rank test will be fitted to determine whether the estimated survival distribution of each time-to-event endpoint differs for patients with PSA decline >= 50% vs. patients with PSA decline < 50%. Cox regression models will be fitted to obtain the estimated hazard ratio for each time-to-event endpoints for patients who had >= 50% PSA decline at 12 weeks vs. those who had not.

  • Progression for a subgroup of patients who have metastatic CRPC and have received enzalutamide treatment [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
    Will be summarized using the estimated proportion and 95% confidence interval. Simple logistic regression model will be used to assess the association between molecular biomarker predictors and these binary secondary endpoints.

  • Progression-free survival [ Time Frame: Time from day 1 of study drug treatment to date of first documented radiographic progression or clinical progression, assessed up to 4 years ] [ Designated as safety issue: No ]
    Will be graphically illustrated using Kaplan-Meier plots of estimated survival distribution for patients (</>= 50%) PSA decline at 12 weeks. Log-rank test will be fitted to determine whether the estimated survival distribution of each time-to-event endpoint differs for patients with PSA decline >= 50% vs. patients with PSA decline < 50%. Cox regression models will be fitted to obtain the estimated hazard ratio for each time-to-event endpoints for patients who had >= 50% PSA decline at 12 weeks vs. those who had not.

  • Time to PSA progression [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
    Will be graphically illustrated using Kaplan-Meier plots of estimated survival distribution for patients (</>= 50%) PSA decline at 12 weeks. Log-rank test will be fitted to determine whether the estimated survival distribution of each time-to-event endpoint differs for patients with PSA decline >= 50% vs. patients with PSA decline < 50%. Cox regression models will be fitted to obtain the estimated hazard ratio for each time-to-event endpoints for patients who had >= 50% PSA decline at 12 weeks vs. those who had not.


Biospecimen Retention:   Samples With DNA

Genomic DNA from individuals will be extracted from collected blood samples (germ line) and tumor biopsies; sonicated to approximately 50 - 200 bp fragments; and used to make a library for paired-end sequencing (Illumina) or for sequencing within the Oregon Health & Science University (OHSU) CLIA laboratory (Ion Torrent sequencing). using established protocols.

We will use whole genome sequencing or Sanger sequencing of cell-free DNA (cfDNA) from blood and DNA from the tumor biopsy specimens. This will enable us to identify molecular features (mutations, including but not limited to the androgen receptor (AR), copy number alterations, and gene fusions) that may predict resistance or early progression despite enzalutamide treatment.


Estimated Enrollment: 65
Study Start Date: March 2013
Estimated Primary Completion Date: October 2017 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Ancillary-Correlative (genetic analysis)
Patients undergo collection of blood and tissue samples at baseline, during administration of enzalutamide and at disease progression for analysis via immunohistochemistry, comparative genome hybridization, and sequencing.
Other: Cytology Specimen Collection Procedure
Correlative studies
Other Name: Cytologic Sampling
Drug: Enzalutamide
Given PO
Other Names:
  • MDV3100
  • Xtandi
Other: Laboratory Biomarker Analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To assess the correlations between baseline molecular features and pathways and prostate-specific antigen (PSA) response (</>= 50% decline) at 12 weeks vs. baseline.

SECONDARY OBJECTIVES:

I. To assess the correlations between the baseline molecular features and pathways and progression-free survival (defined as time from day 1 of study drug treatment to date of radiographic progression or clinical progression), disease-specific survival (defined as the time from day 1 of study drug to date of death from prostate cancer), and overall survival (defined as time from day 1 of study drug treatment to date of death from any cause).

II. To assess the correlations between the baseline molecular features and pathways and time to PSA progression.

III. To identify molecular features and cellular pathways present in tumors from men with metastatic castrate-resistant prostate cancer (CRPC) that are progressing despite enzalutamide treatment.

IV. To explore correlation between baseline molecular features and pathways and objective response.

V. To assess the correlations between the baseline molecular features and pathways and degree of PSA decline at 12 weeks and maximal PSA decline observed while on study.

TERTIARY OBJECTIVES:

I. To assess correlations between cell-free deoxyribonucleic acid (cfDNA) molecular features from blood and molecular features and pathways from the biopsy samples.

II. To assess correlations between cfDNA molecular features and endpoints in the primary and secondary objectives listed above.

OUTLINE:

Patients undergo collection of blood and tissue samples at baseline, during administration of enzalutamide, and at disease progression for analysis via immunohistochemistry, comparative genome hybridization, and sequencing.

After completion of study, patients are followed up every 12 weeks.

  Eligibility

Ages Eligible for Study:   Child, Adult, Senior
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
This is a prospective, single-arm multi-center biomarker study to identify molecular predictive markers for PSA response (</>=50% decline) at 12 weeks vs. baseline in man with metastatic CRPC. We expect to enroll 65 patients over the period of three years, with an approximate of 21 patients per year. All subjects will be treated with MDV3100 and followed on protocol until disease progression or intolerance.
Criteria

Inclusion Criteria:

  • Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features
  • Ongoing androgen deprivation therapy with a gonadotropin-releasing hormone (GnRH) analogue or orchiectomy (i.e., surgical or medical castration); for patients who have not had an orchiectomy, there must be a plan to maintain effective GnRH-analogue therapy for the duration of the trial
  • Radiographic evidence of regional or distant metastases with suspected tumor in an area that is safe to biopsy
  • Willingness to undergo a tumor biopsy at baseline and at disease progression
  • Serum testosterone level < 50 ng/dL at screening
  • Progressive disease by PSA or imaging in the setting of medical or surgical castration; disease progression for study entry is defined as one or more of the following three criteria:

    • PSA progression defined by a minimum of three rising PSA levels with an interval of >= 1 week between each determination; the PSA value at screening should be >= 2 ug/L (2 ng/ml)
    • Soft tissue disease progression defined by Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
    • Bone disease progression defined by two or more new lesions on bone scan
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
  • Clinically able, in the opinion of the investigator, to receive MDV3100 (enzalutamide)
  • Willing and able to give informed consent

Exclusion Criteria:

  • Severe, concurrent disease, infection, or co-morbidity that, in the judgment of the investigator, would make the patient inappropriate for enrollment
  • Metastases in the brain or active epidural disease (NOTE: patients with treated epidural disease are allowed)
  • Platelet count < 75,000/microliter (uL)
  • Prothrombin time (PT) or international normalized ratio (INR) and a partial thromboplastin time (PTT) > 1.5 times the institutional upper limit of normal (ULN)
  • Structurally unstable bone lesions suggesting impending fracture
  • Previous treatment with MDV3100, ARN-509, or BMS-641988
  • Medical contraindications to stopping aspirin, Coumadin or other anticoagulants for 1 week prior to image-guided tumor biopsies
  • Plans to initiate treatment with an investigational agent while on study prior to discontinuation of MDV3100 treatment
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02228265

Locations
United States, California
UCLA / Jonsson Comprehensive Cancer Center Recruiting
Los Angeles, California, United States, 90095
Contact: Matthew B. Rettig    310-794-3565    mrettig@mednet.ucla.edu   
Principal Investigator: Matthew B. Rettig         
University of California at San Francisco - Comprehensive Cancer Center Recruiting
San Francisco, California, United States, 94143-0875
Contact: Eric J. Small    415-353-9865    small@medicine.ucsf.edu   
Principal Investigator: Eric J. Small         
United States, Oregon
OHSU Knight Cancer Institute Recruiting
Portland, Oregon, United States, 97239
Contact: Joshi J. Alumkal    503-494-1091    alumkalj@ohsu.edu   
Principal Investigator: Joshi J. Alumkal         
Sponsors and Collaborators
OHSU Knight Cancer Institute
National Cancer Institute (NCI)
Investigators
Principal Investigator: Joshi Alumkal OHSU Knight Cancer Institute
  More Information

Responsible Party: OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier: NCT02228265     History of Changes
Other Study ID Numbers: 9259  NCI-2014-01438  9259  P30CA069533 
Study First Received: August 25, 2014
Last Updated: April 20, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Prostatic Neoplasms
Adenocarcinoma
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on August 29, 2016