Neoadjuvant Phase 2 Study Comparing the Effects of AR Inhibition With/Without SRC or MEK Inhibition in Prostate Cancer

NCT01990196 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 13-000714NCI-2015-01448
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

Prostate cancer is the most common cancer in men and the second leading cause of cancer death in men. The purpose of this research study is to compare prostate cancers treated with hormone therapy versus prostate cancers treated with hormone therapy plus drugs that directly target cancer cells.

Conditions

Prostate Cancer

Keywords

prostate cancer; hormone therapy; radical prostatectomy

Outcome Measures

Primary Outcomes (1)

• N-cadherin and vimentin expression

  The primary outcome of N-cadherin and vimentin expression will be measured in post-treatment RP specimens. Comparisons amongst the various treatment groups (post-treatment inter-group) will be performed after all data have been collected.

  Prostatectomy will occur during the 2 week "window" between 6 and 8 weeks after enrollment

Study Arms (3)

AR inhibition only

ACTIVE COMPARATOR

AR inhibition only Group 1: degarelix + enzalutamide Endocrine therapy with degarelix and enzalutamide will continue for a minimum of 6 weeks and a maximum of 8 weeks in all groups prior to the planned prostatectomy.

Drug: degarelix; Drug: enzalutamide

AR inhibition plus MEK inhibition

ACTIVE COMPARATOR

AR inhibition plus MEK inhibition Group 2: trametinib + degarelix + enzalutamide In Group 2, treatment with trametinib will begin on Day 29 (i.e. four weeks after initiation of androgen deprivation). Thus, trametinib will be administered for no less than two weeks and no more than four weeks.

Drug: degarelix; Drug: enzalutamide; Drug: trametinib

AR inhibition plus SRC inhibition

ACTIVE COMPARATOR

AR inhibition plus SRC inhibition Group 3: dasatinib + degarelix + enzalutamide In Group 3, treatment with dasatinib will begin on Day 29 (i.e. four weeks after initiation of androgen deprivation). Thus, dasatinib will be administered for no less than two weeks and no more than four weeks.

Drug: degarelix; Drug: enzalutamide; Drug: dasatinib

Interventions

degarelix DRUG

Every 4-week Treatment: A starting dose of 240 mg of Degarelix is taken subcutaneously (SQ) -placed under the skin by injection- the first month. Doses continue every 4 weeks at 80 mg SQ. Dose for a drug may have to be modified based on development of adverse events on a case by case basis as per the judgment of treating physician.

Also known as: Firmagon, FE200486

AR inhibition only; AR inhibition plus MEK inhibition; AR inhibition plus SRC inhibition

enzalutamide DRUG

Once Daily Treatment: A starting dose of 160 mg of Enzalutamide is taken by mouth once daily. Dose for a drug may have to be modified based on development of adverse events on a case by case basis as per the judgment of treating physician.

Also known as: Xtandi, MDV3100

AR inhibition only; AR inhibition plus MEK inhibition; AR inhibition plus SRC inhibition

trametinib DRUG

Once Daily Treatment: If randomized into Group 2, then 2mg of Trametinib is taken by mouth daily. Dose for a drug may have to be modified based on development of adverse events on a case by case basis as per the judgment of treating physician

Also known as: Mekinist

AR inhibition plus MEK inhibition

dasatinib DRUG

Once Daily Treatment: If randomized into Group 3, then 100mg of Dasatinib is taken by mouth daily. Dose for a drug may have to be modified based on development of adverse events on a case by case basis as per the judgment of treating physician

Also known as: Sprycel, BMS-354825

AR inhibition plus SRC inhibition

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.
• Adenocarcinoma of the prostate with planned RP with curative intent as part of standard of care management plan.
• Patient is a candidate for radical prostatectomy.
• Tumor accessible to biopsy.
• Age ≥ 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Estimated life expectancy of ≥ 6 months,
• Adequate organ function: normal renal, liver, hematologic, coagulation and cardiac function:
• Absolute neutrophil count \> 1,500/µL, or platelet count \> 100,000/µL, or hemoglobin \> 5.6 mmol/L (9 g/dL) at the Screening visit,
• Total bilirubin, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) within the normal range at the Screening visit,
• Creatinine \< 1.5 mg/dL at the Screening visit,
• INR \< 1.3 (or \< 3 if on warfarin or other anticoagulants) at the Screening visit,
• Albumin \> 30 g/L (3.0 g/dL) at the Screening visit,
• Left ventricular ejection fraction (LVEF) ≥ LLN by ECHO or MUGA,
• Patients with clinically localized adenocarcinoma of the prostate who are scheduled to undergo radical prostatectomy (RP) with curative intent and have the following clinico-pathologic features: (1) Gleason score sum ≥ 4+3 or any Gleason 5, (2) PSA \> 20, (3) clinical stage ≥ T3a (staging by MRI is allowed).

You may not qualify if:

• Any prior treatment for prostate cancer,
• Any non-adenocarcinoma histologic component,
• Any evidence of lymphatic or hematogenous metastases,
• Clinically significant cardiovascular disease including:
• LVEF \< LLN
• History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months,
• Uncontrolled angina within 3 months,
• Congestive heart failure New York Heart Association (NYHA) class 3 or 4, or patients with history of congestive heart failure NYHA class 3 or 4 in the past, unless a screening echocardiogram or multi-gated acquisition scan performed within 3 months results in a left ventricular ejection fraction that is ≥ 45%,
• Any history of congestive heart failure of any NYHA class for patients assigned to Group 2 (trametinib arm).
• History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes),
• Patients with intra-cardiac defibrillators or permanent pacemakers,
• Hypotension as indicated by systolic blood pressure \< 86 millimeters of mercury (mmHg) at the Screening visit,
• Bradycardia as indicated by a heart rate of \< 50 beats per minute on the Screening ECG,
• Treatment refractory hypertension defined as a blood pressure of systolic \> 140 mmHG and/or diastolic \> 90 mmHG which cannot be controlled by anti-hypertensive therapy,
• QTC ≥ 480 milliseconds,

Sponsors & Collaborators

• Jonsson Comprehensive Cancer Center: lead
• Medivation, Inc.: collaborator
• GlaxoSmithKline: collaborator
• Prostate Cancer Foundation: collaborator
• Astellas Pharma Inc: collaborator
• Novartis: collaborator

Study Sites (1)

University of California, Los Angeles

Los Angeles, California, 90095, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

acetyl-2-naphthylalanyl-3-chlorophenylalanyl-1-oxohexadecyl-seryl-4-aminophenylalanyl(hydroorotyl)-4-aminophenylalanyl(carbamoyl)-leucyl-ILys-prolyl-alaninamide; enzalutamide; trametinib; Dasatinib

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Study Officials

• Robert Reiter, M.D.

  University of California, Los Angeles

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: November 5, 2013
• First Posted: November 21, 2013
• Study Start: September 23, 2014
• Primary Completion: September 23, 2024
• Study Completion (Estimated): September 30, 2026
• Last Updated: August 17, 2025

Record last verified: 2025-08

Locations

US (1)