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

• Sponsor: Barbara Ann Karmanos Cancer Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT01656304
• Collaborator: Genentech, Inc. (Industry)
• Enrollment: 16
• Locations: 2
• Arm: 1
• Duration (Months): 61
• Patients Per Site: 8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	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

Detailed Description

PRIMARY OBJECTIVES:

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

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

SECONDARY OBJECTIVES:

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

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

3. 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.

4. 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 Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of Bevacizumab in PSA Relapse Androgen Independent Prostate Cancer (AVF3952sn)
• Study Start Date: May 1, 2007
• Actual Primary Completion Date: Jan 1, 2012
• Actual Study Completion Date: Jun 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
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

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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.

3. 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.

Secondary Outcome Measures

1. 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).

2. 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.

3. Time to Distant Metastatic Disease [Every 3 months]

   Time to distant metastatic disease using the Kaplan-Meier method

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan	United States	48201
2	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

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Clinical trial summary from the National Cancer Institute's PDQ® database

Publications

None provided.

• Responsible Party: Ulka Vaishampayan, Principal Investigator, Barbara Ann Karmanos Cancer Institute
• ClinicalTrials.gov Identifier: NCT01656304
• Other Study ID Numbers: 2006-064; NCI-2011-00661; NCT00478413
• First Posted: Aug 2, 2012
• Last Update Posted: Jul 31, 2018
• Last Verified: Jul 1, 2018

• Additional relevant MeSH terms: Prostatic Neoplasms; Bevacizumab; Antineoplastic Agents, Immunological; Antibodies; Immunoglobulins; Antibodies, Monoclonal

Study Results

Participant Flow

Arm/Group Title	Treatment (Monoclonal Antibody, Antiangiogenesis)
Arm/Group Description	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. bevacizumab: Given IV laboratory biomarker analysis: Correlative studies
Period Title: Overall Study
STARTED	16
COMPLETED	15
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Treatment (Monoclonal Antibody, Antiangiogenesis)
Arm/Group Description	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. bevacizumab: Given IV laboratory biomarker analysis: Correlative studies
Overall Participants	15
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	70.53 (10.38)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	15 100%
Region of Enrollment (participants) [Number]
United States	15 100%

Outcome Measures

1. Primary Outcome

Title	PSA Response Rate With Bevacizumab Therapy in Androgen Independent Non-metastatic Prostate Cancer
Description	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.
Time Frame	An average every 6 weeks for up to 3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Monoclonal Antibody, Antiangiogenesis)
Arm/Group Description	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. bevacizumab: Given IV laboratory biomarker analysis: Correlative studies
Measure Participants	15
Number [participants]	5 33.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment (Monoclonal Antibody, Antiangiogenesis)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Rate
	Estimated Value	.333
	Confidence Interval	(2-Sided) 80%; .20 to .50
	Parameter Dispersion	Type: Standard Error of the Mean; Value: .1217
	Estimation Comments

2. Primary Outcome

Title	Toxicities Associated With Bevacizumab Therapy
Description	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.
Time Frame	An average of every 2 weeks while on therapy

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Monoclonal Antibody, Antiangiogenesis)
Arm/Group Description	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. bevacizumab: Given IV laboratory biomarker analysis: Correlative studies
Measure Participants	15
Number [participants]	14 93.3%

3. Primary Outcome

Title	Time to PSA Progression (TTPP)
Description	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.
Time Frame	An average every 6 weeks for up to 3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Monoclonal Antibody, Antiangiogenesis)
Arm/Group Description	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. bevacizumab: Given IV laboratory biomarker analysis: Correlative studies
Measure Participants	15
Median (90% Confidence Interval) [months]	2.8

4. Secondary Outcome

Title	Overall Survival of Androgen Independent Non-metastatic Prostate Cancer Patients Treated With Bevacizumab
Description	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).
Time Frame	Every 3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Monoclonal Antibody, Antiangiogenesis)
Arm/Group Description	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. bevacizumab: Given IV laboratory biomarker analysis: Correlative studies
Measure Participants	15
Count of Participants [Participants]	13 86.7%

5. Secondary Outcome

Title	The Change in PSA Velocity With Bevacizumab Therapy in Androgen Independent Non-metastatic Prostate Cancer
Description	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 Frame	Baseline, every 6 weeks while on therapy, and then every 3 months thereafter

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Monoclonal Antibody, Antiangiogenesis)
Arm/Group Description	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. bevacizumab: Given IV laboratory biomarker analysis: Correlative studies
Measure Participants	15
Pre-therapy	2.64
On therapy	1.87

6. Secondary Outcome

Title	Time to Distant Metastatic Disease
Description	Time to distant metastatic disease using the Kaplan-Meier method
Time Frame	Every 3 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Monoclonal Antibody, Antiangiogenesis)
Arm/Group Description	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. bevacizumab: Given IV laboratory biomarker analysis: Correlative studies
Measure Participants	15
Median (90% Confidence Interval) [months]	7.9

Adverse Events

Arm/Group Title	Treatment (Monoclonal Antibody, Antiangiogenesis)
Arm/Group Description	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. bevacizumab: Given IV laboratory biomarker analysis: Correlative studies
All Cause Mortality
	Treatment (Monoclonal Antibody, Antiangiogenesis)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Treatment (Monoclonal Antibody, Antiangiogenesis)
	Affected / at Risk (%)	# Events
Total	4/16 (25%)
Renal and urinary disorders
Proteinuria	1/16 (6.3%)	1
Vascular disorders
Hypertension	2/16 (12.5%)	2
Pulmonary Embolism	1/16 (6.3%)	1
Other (Not Including Serious) Adverse Events
	Treatment (Monoclonal Antibody, Antiangiogenesis)
	Affected / at Risk (%)	# Events
Total	13/16 (81.3%)
Blood and lymphatic system disorders
Anemia	2/16 (12.5%)	2
Gastrointestinal disorders
GERD	1/16 (6.3%)	1
Constipation	1/16 (6.3%)	1
Diarrhea	3/16 (18.8%)	3
Hemorrhage GI	1/16 (6.3%)	1
Hemorrhage GU	1/16 (6.3%)	1
Hemorrhage GU-prostate/urethra	1/16 (6.3%)	1
Hemorrhage oral cavity	1/16 (6.3%)	1
nausea	2/16 (12.5%)	2
Vomiting	1/16 (6.3%)	1
General disorders
Chills	1/16 (6.3%)	1
Edema	1/16 (6.3%)	1
Fatigue	7/16 (43.8%)	7
Generalized Pain	1/16 (6.3%)	1
Injury, poisoning and procedural complications
Bruising	1/16 (6.3%)	1
Investigations
ALT increase	1/16 (6.3%)	1
AST Increase	2/16 (12.5%)	2
Elevated Creatinine	2/16 (12.5%)	2
Leukopenia	1/16 (6.3%)	1
Thrombocytopenia	1/16 (6.3%)	1
weight loss	1/16 (6.3%)	1
Metabolism and nutrition disorders
Anorexia	1/16 (6.3%)	1
Hyperglycemia	1/16 (6.3%)	1
Hypoglycemia	1/16 (6.3%)	1
Hyponatremia	1/16 (6.3%)	1
Musculoskeletal and connective tissue disorders
bone pain	1/16 (6.3%)	1
Lower Extremity swelling	1/16 (6.3%)	1
myalgia	2/16 (12.5%)	2
Weakness	1/16 (6.3%)	1
Nervous system disorders
headache	1/16 (6.3%)	1
Renal and urinary disorders
Hematuria	2/16 (12.5%)	2
Proteinuria	6/16 (37.5%)	6
Urine color change	1/16 (6.3%)	1
Respiratory, thoracic and mediastinal disorders
Cough	1/16 (6.3%)	1
Hemorrhage nose	2/16 (12.5%)	2
Vascular disorders
Hypertension	1/16 (6.3%)	8

Limitations/Caveats

There was a small sample size.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.