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

Phase 2

Completed

• Conditions: Adenocarcinoma of the Prostate; Stage I Prostate Cancer; Stage IIA Prostate Cancer; Recurrent Prostate Cancer; Stage IIB Prostate Cancer; Stage III Prostate Cancer
• Interventions: Biological: bevacizumab; Other: laboratory biomarker analysis

• Registration Number: NCT01656304
• Lead Sponsor: Barbara Ann Karmanos Cancer Institute

Brief Summary

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

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.

Study Timeline

• Study Start: 2007-05
• Primary Completion: 2012-01
• Study Completion: 2012-06
• Study First Submitted: 2012-07-30
• Study First Submitted QC: 2012-08-01
• Study First Posted: 2012-08-02
• Results First Submitted: 2014-06-06
• Results First Submitted QC: 2014-06-06
• Results First Posted: 2014-07-08
• Status Verified: 2018-07
• Last Update Submitted: 2018-07-01
• Last Update Posted: 2018-07-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 16

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (monoclonal antibody, antiangiogenesis)	bevacizumab	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.
Treatment (monoclonal antibody, antiangiogenesis)	laboratory biomarker analysis	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.

Primary Outcome Measures

Name	Time	Method
Time to PSA Progression (TTPP)	An average every 6 weeks for up to 3 months	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.
PSA Response Rate With Bevacizumab Therapy in Androgen Independent Non-metastatic Prostate Cancer	An average every 6 weeks for up to 3 months	A PSA response will be considered a PSA decline of at least 50% must be confirmed by a second PSA value four or more weeks later. The reference PSA for these declines should be a PSA measured within 2 weeks prior to the initiation of therapy. Response rates will be summarized by point estimates and Wilson type 80% confidence intervals.
Toxicities Associated With Bevacizumab Therapy	An average of every 2 weeks while on therapy	Toxicity rates will be summarized by point estimates and Wilson type 90% 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.

Secondary Outcome Measures

Name	Time	Method
The Change in PSA Velocity With Bevacizumab Therapy in Androgen Independent Non-metastatic Prostate Cancer	Baseline, every 6 weeks while on therapy, and then every 3 months thereafter	PSA velocity with bevacizumab therapy in androgen independent non-metastatic prostate cancer pre-therapy, as well as, PSA velocity with bevacizumab therapy while on therapy.
Time to Distant Metastatic Disease	Every 3 months	Time to distant metastatic disease using the Kaplan-Meier method
Overall Survival of Androgen Independent Non-metastatic Prostate Cancer Patients Treated With Bevacizumab	Every 3 months	Overall survival of androgen independent non-metastatic prostate cancer patients treated with bevacizumab. The number of patients still alive at the end of the study (median K-M estimate cannot be obtained due to the 86.7% censoring rate).

Trial Locations

Locations (2)

Barbara Ann Karmanos Cancer Institute; 🇺🇸 Detroit, Michigan, United States

Henry Ford Hospital; 🇺🇸 Detroit, Michigan, United States