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

NCT02881242 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 16-001044NCI-2016-01201
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Hormone-Resistant Prostate Cancer; Metastatic Prostate Carcinoma; Recurrent Prostate Carcinoma; Stage IV Prostate Cancer

Outcome Measures

Primary Outcomes (2)

• PSA response rate

  At 12 weeks

• 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.

  Up to 24 weeks

Secondary Outcomes (11)

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

  Baseline up to 24 weeks

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

  Baseline up to 24 weeks

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

  Up to 30 months

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

  Up to 30 months

• Maximal PSA response

  Up to 30 months

Other Outcomes (1)

• ctDNA genomic aberrations, assessed by exome sequencing

  Up to 24 weeks

Study Arms (1)

Treatment (trametinib)

EXPERIMENTAL

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; Drug: Trametinib

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (trametinib)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Treatment (trametinib)

Trametinib DRUG

Given PO

Also known as: GSK1120212, JTP-74057, MEK Inhibitor GSK1120212, Mekinist

Treatment (trametinib)

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Jonsson Comprehensive Cancer Center: lead
• Stand Up To Cancer: collaborator
• Novartis: collaborator
• Prostate Cancer Foundation: collaborator

Study Sites (1)

UCLA / Jonsson Comprehensive Cancer Center

Los Angeles, California, 90095, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

trametinib

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Study Officials

• Matthew Rettig

  UCLA / Jonsson Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 23, 2016
• First Posted: August 26, 2016
• Study Start: January 30, 2018
• Primary Completion: January 31, 2024
• Study Completion: January 31, 2025
• Last Updated: May 1, 2023

Record last verified: 2023-04

Locations

US (1)