Genomic Guided Therapy With Dasatinib or Nilutamide in Metastatic Castration-Resistant Prostate Cancer

NCT00918385 | Terminated Phase 2 Results DMC

• 2 other identifiers: Pro00012159CA180-263
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 3

Brief Summary

This is a phase II multi-center study to determine the clinical impact of using a patient-specific genomic expression signature of androgen receptor (AR) activity to determine therapy for patients with castration-resistant metastatic prostate cancer (CRPC). After patient eligibility is determined, the genomic signature will be applied to fresh frozen tissue harvested from a metastatic lesion during image-guided biopsy. After assessing for androgen receptor activity, the investigators will select patients for either continued androgen manipulation with nilutamide (high AR activity) or targeted therapy with dasatinib (low AR activity). Once patients develop a first progression on either arm, patients will receive combination therapy with dasatinib and nilutamide. The primary aim is to estimate the median progression free survival in men with CRPC treated according to tumor AR activity. The investigators hypothesize that by treating men based upon AR activity, median progression free survival (PFS) will improve from a historical median of 3.0 months to 6.0 months.

Conditions

Prostate Cancer

Keywords

hormone resistant prostate cancer; castration resistant prostate cancer; hormone refractory prostate cancer; metastatic prostate cancer; hormonal therapy; antiandrogen therapy; androgen receptor; nilutamide; dasatinib; genomics; genomic signature; genomic predictor; genomic analysis; genomic expression profile

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  PFS is the interval from start of monotherapy until first disease progression or death, whichever occurred first.

  During monotherapy ( at least 12 weeks)

Secondary Outcomes (2)

• Overall Response Rate of Men With High AR Activity

  During monotherapy (at least 12 weeks)

• Overall Response Rate of Men With Low AR Activity

  During dasatinib monotherapy ( at least 12 weeks)

Study Arms (2)

1

ACTIVE COMPARATOR

High Androgen Receptor (AR) activity

Drug: Nilutamide

2

ACTIVE COMPARATOR

Low Androgen Receptor (AR) activity

Drug: Dasatinib

Interventions

Nilutamide DRUG

Nilutamide 150mg orally each day for 28 days per cycle. After first progression, Nilutamide 150mg orally each day in combination with Dasatinib 100mg orally each day for 28 days per cycle.

Also known as: Nilandron

1

Dasatinib DRUG

Dasatinib 100mg orally daily x 28 days per cycle. After first progression, Dasatinib 100mg orally each day in combination with Nilutamide 150mg orally each day for 28 days per cycle.

Also known as: Sprycel

2

Eligibility Criteria

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

You may qualify if:

• Confirmed diagnosis of adenocarcinoma of the prostate.
• Radiographic evidence of metastatic disease amenable to image-guided biopsy.
• Testosterone \<50ng/dL on androgen deprivation therapy (ADT). ADT must continue while on study.
• The patient must have discontinued antiandrogens 30 days prior to baseline PSA unless the patient did not respond to anti-androgen therapy or experienced a decline in PSA lasting \< 3 months after starting antiandrogen therapy.
• Evidence of disease progression on ADT.
• Patients must have adequate organ and marrow function as defined below:
• Hemoglobin \>9.0g/dL (without transfusion of PRBC)
• ANC/AGC \>1,500/μl
• Platelets \>75,000/μl
• Total bilirubin \< 2.0 times the institutional ULN
• Creatinine \<1.5 times the institutional ULN
• PT or INR and aPTT \< 1.5 times the institutional ULN
• AST and ALT \<2.5 x ULN
• Age \> 18 years
• Ability to take oral medications (pills must be swallowed whole)

You may not qualify if:

• Patients who have received prior treatment with nilutamide or dasatinib
• Patients who have not recovered to Grade 1 or Grade 0 from the toxic effects of prior investigational therapy, biologic therapy, hormonal therapy (other than ADT), immunotherapy, or chemotherapy
• Medical contraindications to stopping aspirin or coumadin for 1 week prior to image-guided tumor biopsy AND while on dasatinib treatment.
• History of the following cardiac related conditions:
• Uncontrolled angina, congestive heart failure or MI within (6 months)
• Diagnosed congenital long QT syndrome
• Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de pointes)
• Prolonged QTc interval on pre-entry electrocardiogram (\> 450 msec)
• Subjects with hypokalemia or hypomagnesemia if it cannot be corrected prior to dasatinib administration
• History of significant bleeding disorder unrelated to cancer.
• Concomitant use of Category I drugs that are generally accepted to have a risk of causing Torsades de Pointes including: (These medications can be stopped while the patient is on the protocol and the patient needs to be off the drugs for at least 7 days prior to starting dasatinib)
• Patients who have a history of amiodarone use.
• Clinically significant pericardial or pleural effusion or severe respiratory insufficiency
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (requiring antifungal, antibiotic or antiviral therapy), symptomatic congestive heart failure (NYHC II or greater, unstable angina pectoris, cardiac arrhythmia (uncontrolled SVT or any VT), or psychiatric illness/social situations that would limit compliance with study requirements.
• Patients with a medical contraindication to image-guided biopsies

Sponsors & Collaborators

• Duke University: lead
• Bristol-Myers Squibb: collaborator

Study Sites (3)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

University of Washington/Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

Related Publications (1)

• Mendiratta P, Mostaghel E, Guinney J, Tewari AK, Porrello A, Barry WT, Nelson PS, Febbo PG. Genomic strategy for targeting therapy in castration-resistant prostate cancer. J Clin Oncol. 2009 Apr 20;27(12):2022-9. doi: 10.1200/JCO.2008.17.2882. Epub 2009 Mar 16.

  PMID: 19289629 BACKGROUND

MeSH Terms

Conditions

Prostatic Neoplasms; Bulbo-Spinal Atrophy, X-Linked

Interventions

nilutamide; 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; Muscular Atrophy, Spinal; Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Motor Neuron Disease; Neuromuscular Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Dr. Daniel George
• Organization: Duke University

daniel.george@duke.edu

(919) 668 4615

Study Officials

• Daniel George, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: June 10, 2009
• First Posted: June 11, 2009
• Study Start: May 1, 2009
• Primary Completion: February 1, 2012
• Study Completion: August 1, 2013
• Last Updated: October 29, 2014
• Results First Posted: October 29, 2014

Record last verified: 2014-09

Locations

US (3)