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Bevacizumab in Treating Patients With Relapsed Prostate Cancer That Did Not Respond to Hormone Therapy

This study has been completed.
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
Ulka Vaishampayan, Barbara Ann Karmanos Cancer Institute
ClinicalTrials.gov Identifier:
NCT01656304
First received: July 30, 2012
Last updated: June 6, 2014
Last verified: June 2014
  Purpose

This pilot phase II trial studies how well giving bevacizumab works in treating patients with relapsed prostate cancer that did not respond to hormone therapy. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or tumor-killing substances to them. Bevacizumab may also stop the growth of prostate cancer by blocking blood flow to the tumor


Condition Intervention Phase
Adenocarcinoma of the Prostate
Recurrent Prostate Cancer
Stage I Prostate Cancer
Stage IIA Prostate Cancer
Stage IIB Prostate Cancer
Stage III Prostate Cancer
Biological: bevacizumab
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of Bevacizumab in PSA Relapse Androgen Independent Prostate Cancer (AVF3952sn)

Resource links provided by NLM:


Further study details as provided by Barbara Ann Karmanos Cancer Institute:

Primary Outcome Measures:
  • PSA Response Rate With Bevacizumab Therapy in Androgen Independent Non-metastatic Prostate Cancer [ Time Frame: An average every 6 weeks for up to 3 months ] [ Designated as safety issue: No ]
    Response rates will be summarized by point estimates and Wilson type 80% confidence intervals.

  • Toxicities Associated With Bevacizumab Therapy [ Time Frame: An average of every 2 weeks while on therapy ] [ Designated as safety issue: Yes ]
    Toxicity rates will be summarized by point estimates and Wilson type 80% confidence intervals. Toxicities will be graded per the National Cancer Institute (NCI) Common Toxicity Criteria (CTC), and PSA response will be determined as per PSA Working Group response criteria. Censored time to PSA progression will be estimated with standard Kaplan-Meier methodology.

  • Time to PSA Progression (TTPP) [ Time Frame: An average every 6 weeks for up to 3 months ] [ Designated as safety issue: No ]
    TTPP will be measured from protocol registration to appearance of PSA progression as defined by the criteria of the PSA Working Group response criteria. The end point for progression will be calculated at the time a 25% increase in PSA has been achieved. PSA velocity will also be calculated as change in PSA doubling time pre and post therapy and the rate of PSA rise pre- and post-therapy.


Secondary Outcome Measures:
  • Overall Survival of Androgen Independent Non-metastatic Prostate Cancer Patients Treated With Bevacizumab [ Time Frame: Every 3 months ] [ Designated as safety issue: No ]
  • The Change in PSA Velocity With Bevacizumab Therapy in Androgen Independent Non-metastatic Prostate Cancer [ Time Frame: Baseline, every 6 weeks while on therapy, and then every 3 months thereafter ] [ Designated as safety issue: No ]
  • Time to Distant Metastatic Disease [ Time Frame: Every 3 months ] [ Designated as safety issue: No ]
  • Circulating Tumor Cell Count [ Time Frame: Baseline, at week 12 ] [ Designated as safety issue: No ]
  • Changes in Levels of N Terminal Collagen Peptide and Bone-specific Alkaline Phosphatase With Bevacizumab Therapy [ Time Frame: Baseline, week 7 or 12, and post-therapy ] [ Designated as safety issue: No ]
  • Correlation of Urine NTX and Serum BSAP Levels With Time to PSA Progression [ Time Frame: Baseline, week 7 or 12 and post-therapy ] [ Designated as safety issue: No ]

Enrollment: 16
Study Start Date: May 2007
Study Completion Date: June 2012
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (monoclonal antibody, antiangiogenesis)
Patients receive bevacizumab IV over 30-90 minutes once every 14 days. Courses repeat every 14 days in the absence of disease progression and unacceptable toxicity.
Biological: bevacizumab
Given IV
Other Names:
  • anti-VEGF humanized monoclonal antibody
  • anti-VEGF monoclonal antibody
  • Avastin
  • rhuMAb VEGF
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. The rate of prostate-specific antigen (PSA) response with avastin (bevacizumab) therapy in androgen independent non-metastatic prostate cancer.

II. Toxicities associated with avastin therapy. III. Time to PSA progression.

SECONDARY OBJECTIVES:

I. Overall survival of androgen independent non-metastatic prostate cancer patients treated with avastin.

II. The change in PSA velocity with avastin therapy in androgen-independent non-metastatic prostate cancer.

III. Time to distant metastatic disease. IV. Circulating tumor cell count. V. Changes in levels of N terminal collagen peptide and bone-specific alkaline phosphatase with avastin therapy.

VI. Correlation of crosslinked N-telopeptide of type I collagen (NTX) and serum B-Cell-Specific Activator Protein (BSAP) levels with time to PSA progression.

OUTLINE:

Patients receive bevacizumab intravenously (IV) over 30-90 minutes once every 14 days. Courses repeat every 14 days in the absence of disease progression and unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months.

  Eligibility

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

Inclusion Criteria:

  • A histologic diagnosis of prostate adenocarcinoma.
  • No evidence of bone/visceral metastases as visualized on standard imaging such as bone scan, chest X-ray, CT scan or MRI of abdomen and pelvis.
  • PSA-only progression despite androgen deprivation therapy. PSA progression is defined as 3 rising levels, with a minimum interval of 2 weeks between each determination. The last determination must have a minimum value of

    1ng/ml and be determined within two weeks prior to registration. If the second or third confirmatory value is less than the previous value, the patient will still be eligible if a repeat value (No. 4) is found to be greater than all the prior values.

  • If patient has been on antiandrogen in the past 28 days, then PSA progression after withdrawal period (28 days for flutamide and 42 days for bicalutamide or nilutamide) is required.
  • ECOG performance status of 0-1.
  • No prior avastin therapy.
  • No investigational or commercial agents or therapies (except LHRH agonists) may be administered concurrently with the intent to treat the patient's malignancy. Patients on LHRH agonists must continue the use of LHRH agonist therapy. Bisphosphonates can be administered per treating physician discretion.
  • At least 4 weeks must have elapsed since prior systemic therapy, except for LHRH analogue therapy and steroids. If steroids are being used for therapy of prostate cancer, these should be discontinued prior to starting avastin therapy.
  • Age ≥ 18 years.
  • Life expectancy of at least 6 months.
  • Ability to understand and the willingness to sign a written informed consent that is approved by the Institutional Human Investigation Committee.
  • Use of effective means of contraception in subjects.

Exclusion Criteria:

Inability to comply with study and/or follow-up procedures.

  • Inadequately controlled hypertension (defined as systolic blood pressure >150 and/or diastolic blood pressure > 100 mmHg on antihypertensive medications).
  • Any prior history of hypertensive crisis or hypertensive encephalopathy.
  • New York Heart Association (NYHA) Grade II or greater congestive heart failure (see Appendix E).
  • History of myocardial infarction or unstable angina within last 12 months prior to study enrollment.
  • History of stroke or transient ischemic attack within 6 months prior to study enrollment.
  • Known CNS disease.
  • Significant vascular disease (e.g., aortic aneurysm, aortic dissection).
  • Symptomatic peripheral vascular disease.
  • Evidence of bleeding diathesis or coagulopathy.
  • Patients on anticoagulants are allowed if patient has been on therapy for at least 4 weeks and patient has no acute thromboembolic activity.
  • Major surgical procedure, open biopsy, or significant traumatic injury within. 28 days prior to study enrollment or anticipation of need for major surgical procedure during the course of the study.
  • Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to study enrollment.
  • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment.
  • Serious, non-healing wound, ulcer, or bone fracture.
  • Proteinuria at screening as demonstrated by:

    1. Urine protein:creatinine (UPC) ratio ≥ 1.0 at screening

  • Known hypersensitivity to any component of avastin.
  • Refusal to use effective means of contraception.
  • Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to avastin.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Patients with immune deficiency such as HIV-positive patients or those receiving combination anti-retroviral therapy are excluded from the study because of lack of safety data for avastin in these patients.
  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: NCT01656304

Locations
United States, Michigan
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
Henry Ford Hospital
Detroit, Michigan, United States, 48202
Sponsors and Collaborators
Barbara Ann Karmanos Cancer Institute
Genentech, Inc.
Investigators
Principal Investigator: Ulka Vaishampayan Barbara Ann Karmanos Cancer Institute
  More Information

Additional Information:
No publications provided

Responsible Party: Ulka Vaishampayan, Principal Investigator, Barbara Ann Karmanos Cancer Institute
ClinicalTrials.gov Identifier: NCT01656304     History of Changes
Obsolete Identifiers: NCT00478413
Other Study ID Numbers: 2006-064, NCI-2011-00661
Study First Received: July 30, 2012
Results First Received: June 6, 2014
Last Updated: June 6, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Adenocarcinoma
Prostatic Neoplasms
Carcinoma
Genital Diseases, Male
Genital Neoplasms, Male
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Prostatic Diseases
Urogenital Neoplasms
Antibodies
Antibodies, Monoclonal
Bevacizumab
Immunoglobulins
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antineoplastic Agents
Growth Inhibitors
Growth Substances
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014