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

This study has been withdrawn prior to enrollment.
(Sponsor withdrew drug.)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier:
NCT00244920
First received: October 25, 2005
Last updated: May 24, 2012
Last verified: May 2011
  Purpose

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.


Condition Intervention Phase
Prostate Cancer
Drug: bicalutamide
Drug: leuprolide acetate
Drug: squalamine lactate
Procedure: adjuvant therapy
Procedure: antiandrogen therapy
Procedure: antiangiogenesis therapy
Procedure: conventional surgery
Procedure: neoadjuvant therapy
Procedure: releasing hormone agonist therapy
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by OHSU Knight Cancer Institute:

Primary Outcome Measures:
  • Tumor response in terms of tumor volume as measured by transrectal ultrasound before and after neoadjuvant treatment [ Designated as safety issue: No ]
  • Tumor response in terms of conventional histopathology as measured by prostatectomy specimens and Gleason scores in comparison to pre-treatment biopsies [ Designated as safety issue: No ]
  • 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 [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety, feasibility, and tolerability as measured by CTCAE v3.0 [ Designated as safety issue: Yes ]
  • Prostate-specific antigen (PSA) serology as measured by PSA value during and after completion of study treatment [ Designated as safety issue: No ]
  • Survival for up to 3 years after completion of study treatment [ Designated as safety issue: No ]

Enrollment: 0
Study Start Date: January 2002
Study Completion Date: June 2007
Primary Completion Date: June 2007 (Final data collection date for primary outcome measure)
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.

  Eligibility

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

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00244920

Sponsors and Collaborators
OHSU Knight Cancer Institute
Investigators
Study Chair: Mitchell Sokoloff, MD, FACS OHSU Knight Cancer Institute
  More Information

No publications provided

Responsible Party: OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier: NCT00244920     History of Changes
Other Study ID Numbers: CDR0000446087, OHSU-MSI-1256F-204, OHSU-IRB-357
Study First Received: October 25, 2005
Last Updated: May 24, 2012
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by OHSU Knight Cancer Institute:
adenocarcinoma of the prostate
stage III prostate cancer

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Androgen Antagonists
Bicalutamide
Hormones
Leuprolide
Squalamine
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Fertility Agents, Female
Fertility Agents
Reproductive Control Agents
Therapeutic Uses
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Anticarcinogenic Agents
Protective Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors

ClinicalTrials.gov processed this record on August 21, 2014