MDX-010 for Advanced Prostate Cancer

This study has been completed.
Sponsor:
Collaborators:
U.S. Army Medical Research Acquisition Activity
Medarex
Information provided by (Responsible Party):
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00170157
First received: September 13, 2005
Last updated: December 20, 2013
Last verified: December 2013
  Purpose

A total of 108 males with advanced prostate cancer will be enrolled into this study. Patients must have undergone prostate cancer staging within 180 days of enrollment. 54 patients will be randomized to receive hormone therapy alone and 54 patients will be randomized to receive hormone therapy plus the MDX-010 therapy.


Condition Intervention Phase
Prostatic Neoplasms
Drug: Combination Androgen Ablative Therapy
Biological: MDX-010 therapy
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Immunotherapeutic Trial: Combination Androgen Ablative Therapy and CTLA-4 Blockade as a Treatment for Advanced Prostate Cancer

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Number of Participants Progression-free at 18 Months [ Time Frame: 18 months from the start of AA therapy ] [ Designated as safety issue: No ]
    PSA progression is defined as a rise in PSA to >4.0 ng/mL demonstrated twice in measurements taken two weeks apart.


Secondary Outcome Measures:
  • Number of Participants With an Initial Prostate-specific Antigen (PSA) Response [ Time Frame: Duration of study (up to 18 months) ] [ Designated as safety issue: No ]
    Initial PSA response is defined as the response to the initially assigned treatment (prior to crossing over). A response is defined as a decrease in PSA 50% or greater that is confirmed 2 consecutive measurements taken at least 2 weeks apart.


Enrollment: 112
Study Start Date: June 2005
Study Completion Date: November 2010
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Androgen Ablative (AA) therapy + MDX-010

3 months of concurrent androgen ablative (AA) therapy + MDX-010

Androgen ablative (AA) therapy is received a combined regimen of GnRH agonist and androgen receptor blocker. GnRH agonists must be in the form of a 1 month depot of either leuprolide acetate (Lupron) 7.5 mg intramuscular (IM), or goserelin acetate (Zoladex) 3.6 mg subcutaneous (SC) and will be administered on Day 0 (baseline), Day 28 and Day 56. Androgen receptor blockade may be provided by oral administration of either flutamide (Eulexin) 250 mg orally 3 times daily, or bicalutamide (Casodex) 50 mg orally once daily.

MDX-010 is received as an infusion at a dose of 3.0 mg/kg on day 7.

Drug: Combination Androgen Ablative Therapy

Lupron 7.5 mg monthly times 3 months (leuprolide acetate)

Casodex 50 mg daily times 3 months (Bicalutamide)

Other Names:
  • Lupron or leuprolide acetate
  • Casodex or Bicalutamide
Biological: MDX-010 therapy
MDX-010 3 mg/kg one time dose (Ipilimumab)
Other Name: MDX-010 or Ipilimumab
Active Comparator: Androgen ablative (AA)

3 months of initial AA therapy alone

Androgen ablative (AA) therapy is received a combined regimen of GnRH agonist and androgen receptor blocker. GnRH agonists must be in the form of a 1 month depot of either leuprolide acetate (Lupron) 7.5 mg intramuscular (IM), or goserelin acetate (Zoladex) 3.6 mg subcutaneous (SC) and will be administered on Day 0 (baseline), Day 28 and Day 56. Androgen receptor blockade may be provided by oral administration of either flutamide (Eulexin) 250 mg orally 3 times daily, or bicalutamide (Casodex) 50 mg orally once daily.

Drug: Combination Androgen Ablative Therapy

Lupron 7.5 mg monthly times 3 months (leuprolide acetate)

Casodex 50 mg daily times 3 months (Bicalutamide)

Other Names:
  • Lupron or leuprolide acetate
  • Casodex or Bicalutamide

Detailed Description:

This trial has been designed to ensure the capture of both treatment mechanism-specific data as well as clinically meaningful data within a relatively compressed study interval. Thus, this trial is constructed around a single inductive short-term cycle of AA therapy.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed adenocarcinoma of the prostate staged within 180 days of study enrollment, stage with or without metastatic disease, with the exclusion of central nervous system metastases; includes post radical prostatectomy patients with a rising PSA.
  • An initial PSA greater than 4.0 using the Hybritech Assay. For those participants who have received hormone therapy less than or equal to 21 days, a documented PSA of greater than or equal to 4.0 prior to initiation of hormone therapy is acceptable. For those participants who are post radical prostatectomy, a rising PSA is acceptable.
  • Adequate organ function defined as: WBC greater than 3,000; platelets greater than 75,000; total bilirubin less than 1.5mg; transaminases less than 2.5 times upper limit of normal; serum creatinine less than 2.0 mg or calculated creatinine clearance greater than 60 mL. All values must be obtained 14 days prior to study entry.
  • ECOG performance status of 0 2.
  • Patients must be 18 years of age at the time of study entry and able to understand and sign informed consent.

Exclusion Criteria:

  • Underlying other serious medical condition which, in the opinion of the investigator, precludes study participation. This includes immuno-suppressive disease such as AIDS or autoimmune disorders such as multiple sclerosis or lupus.
  • Patients not recovered from major infections and/or surgical procedures.
  • Prior hormonal therapy greater than 21 days prior to enrollment, including estrogens, LH/RH agonists, antiandrogens, or 5-reductase inhibitors.
  • Recent less than 3 months of informed consent usage of immuno suppressive medications including steroids, Immuran, Cyclosporin. Topical or inhalational steroid use is permissible.
  • For participants who elect to undergo the baseline transrectal needle biopsy of the prostate, current usage of systemic anticoagulation therapy, i.e. heparin or coumadin or inability to discontinue aspirin, aspirin-containing products or ibuprofen for seven days prior to the prostate biopsies required for this study.
  • Prior systemic chemotherapy.
  • Prior radiation therapy to the prostate
  • Concurrent malignancy, except for adequately treated basal cell or squamous cell skin cancer.
  • Prior malignancy, unless the patient has been cancer free for five years or more.
  • Uncontrolled underlying medical or psychiatric illness, or serious active infections.
  • Patient unwilling to complete all required follow-up visits.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00170157

Locations
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
U.S. Army Medical Research Acquisition Activity
Medarex
Investigators
Principal Investigator: Eugene D. Kwon, M.D. Mayo Clinic
  More Information

Additional Information:
No publications provided

Responsible Party: Mayo Clinic
ClinicalTrials.gov Identifier: NCT00170157     History of Changes
Other Study ID Numbers: MC0253, 1564-02, MC0253
Study First Received: September 13, 2005
Results First Received: May 3, 2013
Last Updated: December 20, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Androgens
Leuprolide
Bicalutamide
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses
Fertility Agents, Female
Fertility Agents
Reproductive Control Agents
Androgen Antagonists
Hormone Antagonists

ClinicalTrials.gov processed this record on April 17, 2014