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Hormone-Resistant Prostate CancerPhase 2NCT02881242

Trametinib in Treating Patients With Progressive Metastatic Hormone-Resistant Prostate Cancer

A Phase 2 study testing Laboratory Biomarker Analysis, Quality-of-Life Assessment and Trametinib in people with Hormone-Resistant Prostate Cancer and Metastatic Prostate Carcinoma, run by Jonsson Comprehensive Cancer Center at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This phase II trial studies how well trametinib works in treating patients with hormone-resistant prostate cancer that is growing or getting worse and has spread to other parts of the body. Trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Read more about this study

Who is it for?
Ages 18 years and older, men only
What is being tested?
Laboratory Biomarker Analysis, Quality-of-Life Assessment and Trametinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
14 participants
Where
1 siteUnited States
Study dates
30 Jan 2018to 31 Jan 2025
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Willing and able to give informed consent
  • Histologically confirmed prostate cancer (not exclusive of adenocarcinoma)
  • mCRPC that has progressed on at least 1 therapy progression (defined as Prostate Cancer Working Group 2 [PCWG2] or at investigators' discretion) approved for treatment of mCRPC, one of which must include abiraterone acetate and/or enzalutamide
  • Metastatic tumor that has been biopsied
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
  • Willing to undergo biopsy of a metastatic lesion at the time of progression
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  • Patients must have ongoing therapy to maintain serum testosterone < 50 ng/dL
  • Absolute neutrophil count > 1,500/uL during screening evaluation
  • Platelet count > 100,000/uL during screening evaluation
  • Hemoglobin > 9 g/dL during screening evaluation
  • Total bilirubin within the reference range during screening evaluation
  • Alanine aminotransferase (ALT) within the reference range during screening evaluation
  • Aspartate aminotransferase (AST) within the reference range during screening evaluation
  • Creatinine < (1.5 mg/dL) during screening evaluation (> 1.5 is allowed if epidermal growth factor receptor [EGFR] > 45 mL/min/1.73 m^2)
  • International normalized ratio (INR) < 1.3 (or < 3 if on warfarin or other anticoagulants) during screening evaluation
  • Left ventricular ejection fraction (LVEF) >= 45% as measured by echocardiogram during screening evaluation
  • Electrocardiogram (EKG) without clinically significant abnormality

Who cannot join

  • A history of retinal vein occlusion (RVO) or risks factors for RVO
  • A history of retinal pigment epithelial detachment (RPED) or risk factors for RPED
  • Clinically significant abnormality on ophthalmologic examination during screening evaluation
  • Clinically significant cardiovascular disease including:
  • LVEF < 45% measured by echocardiogram
  • History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months
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  • Uncontrolled angina within 3 months
  • New York Heart Association (NYHA) class III or IV congestive heart failure
  • Clinically significant abnormality on EKG
  • History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes)
  • Patients with intra-cardiac defibrillators or permanent pacemakers
  • Presence of a comorbid disease or medical condition that would impair the ability of the patient to receive or comply with the study protocol
  • History of interstitial lung disease or pneumonitis
  • Use of any medication or herbal products that may have hormonal anti-prostate cancer activity and/or are known to modulate PSA levels (e.g., saw palmetto) or systemic corticosteroids greater than the equivalent of 10 mg of prednisone per day within 4 weeks of enrollment
  • Prior use of trametinib or other mitogen activated protein kinase (MAPK) inhibitor in any context
  • Known or suspected brain metastasis or active leptomeningeal disease or spinal cord compression
  • Gastrointestinal disorder affecting absorption (e.g., gastrectomy, active peptic ulcer disease within last 3 months, inflammatory bowel disease)
  • Any major surgery, extensive radiotherapy, chemotherapy with delayed toxicity, biologic therapy, or immunotherapy within 30 days of enrollment and/or daily or weekly chemotherapy without the potential for delayed toxicity within 14 days of enrollment
  • Hospitalization within 30 days of enrollment for cancer related events
  • History of another malignancy within the previous 5 years other than curatively treated non-melanoma skin cancer
  • Use of an investigational agent within 4 weeks of enrollment
  • Use of any medications known to affect the serum androgen level
  • Any condition or reason that, in the opinion of the investigator, interferes with the ability of the patient to participate in the trial, which places the patient at undue risk, or complicates the interpretation of safety data

Trial locations and contacts

1 site in 1 country.

United States1 site

  • UCLA / Jonsson Comprehensive Cancer Center

    Los Angeles, California, 90095

Other trials in United States

About this study

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

This phase II trial studies how well trametinib works in treating patients with hormone-resistant prostate cancer that is growing or getting worse and has spread to other parts of the body. Trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Read the detailed description

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.

OUTLINE:

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.

Being tested
Laboratory Biomarker Analysis, Quality-of-Life Assessment, Trametinib
Medical subject headings
Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Quality-of-Life AssessmentOther

    Also called Quality of Life Assessment

    Ancillary studies

  • TrametinibDrug

    Also called GSK1120212, JTP-74057, MEK Inhibitor GSK1120212, Mekinist

    Given PO

Study groups in NCT02881242
Study groupRoleWhat they receive
Treatment (trametinib)ExperimentalPatients receive trametinib PO QD. Treatment continues in the absence of disease progression or unacceptable toxicity.
Receives: Other: Laboratory Biomarker Analysis; Other: Quality-of-Life Assessment; Drug: Trametinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. PSA response rate

    Measured: At 12 weeks

  2. Response rate assessed by RECIST criteria

    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.

    Measured: Up to 24 weeks

Secondary outcomes (11)

  1. Change in markers of cell proliferation (Ki67) and apoptosis (p27), assessed by immunohistochemistry

    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.

    Measured: Baseline up to 24 weeks

  2. Change in trametinib target engagement of MEK1/2 defined by the presence of p-ERK, assessed by immunohistochemistry

    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.

    Measured: Baseline up to 24 weeks

  3. Durability of PSA response as measured by time to PSA progression as defined by PCWG2 guidelines

    Measured: Up to 30 months

  4. Incidence of adverse events, graded according to the Common Terminology Criteria for Adverse Events version 4.0

    Measured: Up to 30 months

  5. Maximal PSA response

    Measured: Up to 30 months

  6. Molecular correlates defined by gene expression, assessed using ribonucleic acid-sequencing, and mutational events, assessed using DNA exome-seq

    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.

    Measured: Up to 24 weeks

  7. Objective radiographic response rate according to RECIST guidelines

    Measured: Up to 24 weeks

  8. Overall survival

    Measured: Time from enrollment until death, assessed for up to 30 months

  9. Quality of life, assessed by FACT-P

    Measured: Up to 30 months

  10. Time to initiation of alternative anti-neoplastic therapy

    Measured: Up to 30 months

  11. Time to radiographic progression

    Measured: Up to 24 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Aug 2016 (estimated)
  2. Study start30 Jan 2018
  3. Primary completion31 Jan 2024 (estimated)
  4. Study completion31 Jan 2025 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
14 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02881242
Sponsor's protocol ID
16-001044
Other IDs
NCI-2016-01201
Status last verified
Apr 2023
First submitted
23 Aug 2016
Last updated
1 May 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Laboratory Biomarker Analysis, Quality-of-Life Assessment and Trametinib in people with Hormone-Resistant Prostate Cancer and Metastatic Prostate Carcinoma, run by Jonsson Comprehensive Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 1 May 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

PSA response rate (time frame: At 12 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02881242.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 May 2023.

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