Clinical trial NCT00111618: Study of AS1404 With Docetaxel in Patients With Hormone Refractory Metastatic Prostate Cancer
Official title: An Open Label, Randomized, Phase II Study of AS1404 in Combination With Docetaxel in Patients With Hormone Refractory Metastatic Prostate Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Prostate Cancer
Keywords: vascular disrupting agent
safety
tolerability
efficacy
hormone refractory prostate cancer
Lead sponsor: Antisoma Research
Sponsor class: INDUSTRY
First posted: 2005-05-25
Enrollment: 70
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this trial is to confirm a safe dose of AS1404, to be given with docetaxel, and to see whether adding AS1404 and docetaxel together improves the outcome of the treatment, when compared to docetaxel alone.

Detailed description: The overall aim of this study is to determine the safety, tolerability and efficacy of AS1404 in combination with docetaxel in patients with hormone refractory metastatic prostate cancer.

Eligibility criteria: Inclusion Criteria:

* Age equal to, or greater than 18 years
* Eastern Cooperative Oncology Group (ECOG) performance status 0-2
* Life expectancy greater than or equal to 3 months
* Histopathologically confirmed adenocarcinoma of the prostate
* Metastatic progressive androgen-independent prostate cancer with no previous chemotherapy treatment
* At least 4 weeks off of flutamide and 6 weeks off of bicalutamide and nilutamide
* Patients who have not undergone surgical castration must continue treatment with an luteinizing hormone-releasing hormone (LHRH) agonist. In those patients where, for some reason, the LHRH agonist has been discontinued prior to entry on the study, it should be reinstituted and disease progression must be documented.
* Hematological and biochemical indices at screening within the following ranges:

  * An absolute neutrophil count of greater than or equal to 1.5 x 10\^9/L;
  * A platelet count of greater than or equal to 100 x 10\^9/L;
  * A hemoglobin level of greater than or equal to 10 g/dL.
* Adequate hepatic and renal function, as defined by:

  * Serum bilirubin less than or equal to upper limit of normal (ULN);
  * SGOT and/or SGPT less than or equal to 1.5 x ULN concomitant with alkaline phosphatase less than or equal to 2.5 x ULN;
  * Serum creatinine less than or equal to 120 micromol/L or creatinine clearance greater than or equal to 60 mL/min.
* Be willing and able to provide written informed consent and, in the opinion of the Investigator, be able to comply with the study assessments and follow-up
* Serum testosterone no greater than 50 ng/mL (chemically castrated patients only)

Exclusion Criteria:

* Decreasing PSA levels after antiandrogen withdrawal
* Previous chemotherapy treatment for prostate cancer
* Patients who have received blood transfusions or growth factors to aid hematological recovery within two weeks of scheduled baseline visit
* Concurrent severe and/or uncontrolled co-morbid medical condition within 2 weeks of screening
* Previous exposure to AS1404 or other vascular targeting agents
* Clinically significant cardiac arrhythmias and known QTc prolongation (interval \>450 msec)
* Evidence of severe or uncontrolled systemic disease that, in the opinion of the Investigator, might interfere with the patient's participation in the study
* A history of alcoholism; drug addiction; or any psychiatric condition, which, in the opinion of the Investigator, would impair the patient's ability to comply with study procedures
* A history of hypersensitivity to taxanes or other drugs formulated with polysorbate 80
* Treatment with the following medications within two weeks of AS1404 administration or the expected need for such treatments during the study period:

  * Medications known to modulate serotonin;
  * Medications known to affect the QT interval;
  * Current treatment with, or the expected need during the treatment period for ketoconazole, erythromycin, troleandomycin, and/or cyclosporine. The use of other agents known to induce, inhibit, or that are metabolized by cytochrome P450-3A4 should be undertaken with caution.
* Concurrent or previous malignancy of a different tumor type within five years of starting the study, except for adequately treated non-melanoma skin cancer
* Clinical or radiological evidence of central nervous system (CNS) metastases
* Symptomatic peripheral neuropathy greater than or equal to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grade II
* Evidence of any other significant clinical disorder or laboratory finding that, in the opinion of the Investigator, compromises the patient safety during study participation
* Participation in any prostate cancer investigational drug study in which the study drug has not subsequently obtained a product license
* Any other concurrent treatment for prostate cancer (with the exception of palliative radiotherapy) other than that specified in the protocol, including the use of herbal remedies, (e.g. saw palmetto)

Primary outcomes:
measure: Laboratory safety
measure: Adverse event monitoring
measure: Electrocardiogram (EKG)
measure: Ophthalmic assessments
measure: Tumor assessment
measure: Time to progression and survival time
measure: Prostate-specific antigen (PSA)
measure: Pharmacokinetic sampling
Secondary outcomes:
Other outcomes:
Locations:
city: Alhambra
country: United States
facility: Central Hematology Oncology Medical Group Inc
state: California
city: Bakersfield
country: United States
facility: Comprehensive Blood and Cancer Center
state: California
city: Burbank
country: United States
facility: Providence Saint Joseph's Medical Center (PSJMC)
state: California
city: Encinitas
country: United States
facility: Pacific Oncology & Hematology Associates
state: California
city: Fullerton
country: United States
facility: Virginia K. Crosson Cancer Center
state: California
city: Long Beach
country: United States
facility: Pacific Shores Medical Group
state: California
city: Los Angeles
country: United States
facility: UCLA Clinical Research Unit
state: California
city: Northridge
country: United States
facility: North Valley Hematology/Oncology Medical Group, The Thomas and Dorothy Leavey Cancer Center
state: California
city: Oxnard
country: United States
facility: Ventura County Hematology-Oncology Specialists
state: California
city: Redondo Beach
country: United States
facility: Cancer Care Associates Medical Group, Inc
state: California
city: Santa Barbara
country: United States
facility: Sansum Santa Barbara Medical Foundation Clinic
state: California
city: Santa Barbara
country: United States
facility: Santa Barbara Hematology Oncology Medical Group, Inc.
state: California
city: Santa Maria
country: United States
facility: Central Coast Medical Oncology Corporation
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center-Cancer Center
state: California
city: Miami
country: United States
facility: University of Miami School of Medicine
state: Florida
city: Atlanta
country: United States
facility: Peachtree Hematology and Oncology
state: Georgia
city: Peoria
country: United States
facility: Oncology Hematology Associates of Central Illinois,PC
state: Illinois
city: New Orleans
country: United States
facility: Ochsner Cancer Institute
state: Louisiana
city: Baltimore
country: United States
facility: The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: St Louis Park
country: United States
facility: Park Nicollet Institute
state: Minnesota
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Bronx,
country: United States
facility: Biomedical Research Alliance of New York (BRANY)
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Staten Island
country: United States
facility: Staten Island Urological Research
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
city: Marshfield
country: United States
facility: Marshfield Clinic Foundation
state: Wisconsin
Study officials:
affiliation: The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
name: Roberto Pili, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Jameson MB, Thompson PI, Baguley BC, Evans BD, Harvey VJ, Porter DJ, McCrystal MR, Small M, Bellenger K, Gumbrell L, Halbert GW, Kestell P; Phase I/II Trials Committee of Cancer Research UK. Clinical aspects of a phase I trial of 5,6-dimethylxanthenone-4-acetic acid (DMXAA), a novel antivascular agent. Br J Cancer. 2003 Jun 16;88(12):1844-50. doi: 10.1038/sj.bjc.6600992.
citation: Seshadri M, Spernyak JA, Maiery PG, Cheney RT, Mazurchuk R, Bellnier DA. Visualizing the acute effects of vascular-targeted therapy in vivo using intravital microscopy and magnetic resonance imaging: correlation with endothelial apoptosis, cytokine induction, and treatment outcome. Neoplasia. 2007 Feb;9(2):128-35. doi: 10.1593/neo.06748.