Hormone Therapy With or Without Squalamine Lactate in Treating Patients Who Are Undergoing a Radical Prostatectomy for Locally Advanced Prostate Cancer

May 24, 2012 updated by: OHSU Knight Cancer Institute

An Open Label Randomized Phase 2 Study To Evaluate The Activity, Tolerability, And Toxicity Of Combined Neoadjuvant Anti-angiogenesis and Androgen Ablation Therapy in Men Undergoing Radical Prostatectomy

RATIONALE: Androgens can cause the growth of prostate cancer cells. Drugs, such as leuprolide and bicalutamide, may stop the adrenal glands from making androgens. Squalamine lactate may stop the growth of prostate cancer by blocking blood flow to the tumor. Giving hormone therapy together with squalamine lactate before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

PURPOSE: This randomized phase II trial is studying how well giving hormone therapy together with squalamine lactate works compared to hormone therapy alone in treating patients who are undergoing a radical prostatectomy for locally advanced prostate cancer.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

  • Compare the effect of neoadjuvant androgen-ablation therapy with vs without squalamine lactate on induced tumor regression and grade migration in patients with locally advanced high-risk adenocarcinoma of the prostate undergoing a radical prostatectomy.
  • Compare the duration of clinical disease-free survival of patients treated with these regimens.
  • Determine the applicability of prostate-specific antigen (PSA) serology as an endpoint determinant in patients treated with these regimens.
  • Compare the feasibility and potential safety effects on wound healing and recovery in patients treated with these regimens before and after a radical prostatectomy.

OUTLINE: This is an open-label, randomized, multicenter study. Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive leuprolide intramuscularly once a month for 3 months and oral bicalutamide once a day for 2 weeks.
  • Arm II: Patients receive leuprolide and bicalutamide as in arm I plus squalamine lactate IV over 4 hours once weekly for 6 weeks.

Seven weeks after beginning treatment, patients in both arms undergo standard radical prostatectomy. Patients then continue to receive leuprolide and bicalutamide with or without squalamine lactate for up to 6 additional weeks.

After completion of study treatment, patients are followed periodically for at least 3 years.

PROJECTED ACCRUAL: A total of 132 patients (66 per treatment arm) will be accrued for this study.

Study Type

Interventional

Phase

  • Phase 2

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

DISEASE CHARACTERISTICS:

  • Histologically confirmed adenocarcinoma of the prostate

    • Locally advanced disease

      • No metastatic disease

  • High-risk characteristics, meeting ≥ 1 of the following criteria:

    • Large, hard tumor on digital exam
    • Aggressive-appearing cancer cells on biopsy
  • Prostate-specific antigen > 10 ng/mL

PATIENT CHARACTERISTICS:

Performance status

  • 0-1

Life expectancy

  • Not specified

Hematopoietic

  • WBC > 1,500/mm^3
  • Platelet count > 100,000/mm^3
  • Hemoglobin > 11.0 g/dL

Hepatic

  • Bilirubin < 2 times upper limit of normal (ULN)
  • SGOT and SGPT < 2 times ULN
  • PT and PTT normal

Renal

  • Creatinine < 1.8 g/dL

Cardiovascular

  • No history of ventricular arrhythmia or dysfunction
  • No congestive heart failure
  • No symptomatic coronary artery disease
  • No prior myocardial infarction
  • No history of thromboembolic disease (e.g., deep vein thrombosis or stroke) within the past 12 months
  • No other significant cardiovascular disease

Pulmonary

  • No pulmonary embolism within the past 12 months
  • No exercise-limiting respiratory disease

Other

  • Fertile patients must use effective barrier method contraception
  • No sexual intercourse for 6 weeks after surgery
  • No uncontrolled diabetes
  • No serious acute infection
  • No other malignancy except nonmelanoma skin cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No prior squalamine lactate

Chemotherapy

  • No prior chemotherapy for prostate cancer
  • No concurrent anticancer chemotherapy

Endocrine therapy

  • No concurrent systemic corticosteroids

Radiotherapy

  • No prior radiotherapy for prostate cancer
  • No concurrent radiotherapy

Surgery

  • No prior surgery for prostate cancer
  • No other concurrent surgery

Other

  • At least 6 weeks since prior and no concurrent use of over-the-counter or herbal drugs that have estrogenic activity
  • No participation in another investigational study within the past 3 months
  • No concurrent participation in another investigational study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Tumor response in terms of tumor volume as measured by transrectal ultrasound before and after neoadjuvant treatment
Tumor response in terms of conventional histopathology as measured by prostatectomy specimens and Gleason scores in comparison to pre-treatment biopsies
Tumor response in terms of molecular markers as measured by changes in VEGF, VEGF-flt-1, and integrin Alpha6Beta4, AlphaVBeta3, and AlphaVBeta5 expression in pre-treatment biopsy and post-treatment prostatectomy specimens

Secondary Outcome Measures

Outcome Measure
Safety, feasibility, and tolerability as measured by CTCAE v3.0
Prostate-specific antigen (PSA) serology as measured by PSA value during and after completion of study treatment
Survival for up to 3 years after completion of study treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

OHSU Knight Cancer Institute

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: Mitchell Sokoloff, MD, FACS, OHSU Knight Cancer Institute

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2002

Primary Completion (Actual)

June 1, 2007

Study Completion (Actual)

June 1, 2007

Study Registration Dates

First Submitted

October 25, 2005

First Submitted That Met QC Criteria

October 25, 2005

First Posted (Estimate)

October 27, 2005

Study Record Updates

Last Update Posted (Estimate)

May 28, 2012

Last Update Submitted That Met QC Criteria

May 24, 2012

Last Verified

May 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000446087
  • OHSU-MSI-1256F-204
  • OHSU-IRB-357

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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