APC8015 and Bevacizumab in Treating Patients With Prostate Cancer

Study Overview
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Brief Summary
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Phase II trial to study the effectiveness of APC8015 combined with bevacizumab in treating patients who have undergone radiation therapy and/or surgery and who have progressive prostate cancer. Biological therapies such as APC8015 use different ways to stimulate the immune system and stop cancer cells from growing. Monoclonal antibodies such as bevacizumab can locate tumor cells and kill them without harming normal cells. Combining monoclonal antibody therapy with biological therapy may kill more cancer cells.

Detailed Description
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OBJECTIVES: I. Determine the efficacy of APC8015 (Provenge) and bevacizumab, in terms of decline in prostate-specific antigen (PSA) value and effect on PSA doubling time, in patients with progressive prostate cancer. II. Determine any immune response in patients treated with this regimen. III. Determine the safety of this regimen in these patients. OUTLINE: Autologous dendritic cells (DCs) are harvested and pulsed with prostatic acid phosphatase-sargramostim fusion protein to produce APC8015 (Provenge). Patients receive APC8015 IV over 30 minutes and bevacizumab IV over 30-60 minutes on day 1. Treatment repeats every 14 days for 3 courses. Patients continue to receive bevacizumab alone every 14 days in the absence of disease progression or unacceptable toxicity. Patients are followed every month.

Official Title
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A Phase II Study Of Prostatic Acid Phosphatase-Pulsed Dendritic Cells (Provenge) In Combination With Bevacizumab In Patients With Serologic Progression Of Prostate Cancer After Definitive Local Therapy

Conditions
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Prostate Cancer

Intervention / Treatment
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* Biological: bevacizumab
* Biological: prostatic acid phosphatase-sargramostim fusion protein
* Biological: sipuleucel-T
* Biological: therapeutic autologous dendritic cells
* Procedure: in vitro-treated peripheral blood stem cell transplantation


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed adenocarcinoma of the prostate Any T, any N, M0 Received prior therapy comprising one of the following regimens for primary prostate cancer: External beam radiotherapy Brachytherapy with or without pelvic external beam radiotherapy Cryosurgery Radical prostatectomy with or without adjuvant or salvage radiotherapy Adjuvant or salvage radiotherapy after radical prostatectomy is allowed provided the following criteria is met: PSA was never greater than 6.0 ng/mL At least 3 months since androgen deprivation Elevated PSA (0.4-6.0 ng/mL) that has increased on 2 measurements taken at least 2 weeks apart No history of or radiological evidence of current CNS disease (e.g., primary brain tumor, seizures not controlled with standard medical therapy, or brain metastases) PATIENT CHARACTERISTICS: Performance status: ECOG 0-1 Life expectancy: At least 12 months Hematopoietic: WBC greater than 2,500/mm^3 Absolute neutrophil count greater than 1,000/mm^3 Platelet count greater than 100,000/mm^3 No prior bleeding disorder Hepatic: Bilirubin no greater than 2 times upper limit of normal (ULN) AST no greater than 2 times ULN Hepatitis B and C negative Renal: Creatinine no greater than 2 times ULN BUN no greater than 2 times ULN Cardiovascular: No clinically significant cardiovascular disease No New York Heart Association grade II-IV heart disease (symptomatic congestive heart failure) No unstable angina pectoris No serious cardiac arrhythmia requiring medication No uncontrolled hypertension No prior myocardial infarction No grade II or greater peripheral vascular disease within the past year No prior deep vein thrombosis Other: Fertile patients must use effective contraception HIV and HTLV I and II negative No other uncontrolled illness, underlying medical condition, psychiatric illness, or social situation that would preclude study participation No ongoing or active infection No active autoimmune disease requiring treatment No significant traumatic injury within the past 4 weeks No serious nonhealing wound, ulcer, or bone fracture No other currently active malignancy except nonmelanoma skin cancer Not currently active if considered by physician as having less than 30% risk of relapse after completion of therapy PRIOR CONCURRENT THERAPY: Biologic therapy: No prior immunotherapy No prior anti-vascular endothelial growth factor therapy Chemotherapy: No prior chemotherapy Endocrine therapy: No prior hormonal therapy (e.g., luteinizing hormone-releasing hormone [LHRH] agonists or antagonists, antiandrogens, estrogens, megestrol, or PC-SPES) for progressive disease Prior hormonal therapy in adjuvant or neoadjuvant setting as primary therapy allowed if at least 3 months since androgen deprivation No concurrent systemic steroid therapy (inhaled or topical steroids allowed) Radiotherapy: No concurrent radiotherapy Surgery: At least 4 weeks since prior major surgery, including open biopsy or needle biopsy of liver No concurrent major surgery Other: At least 10 days since prior aspirin At least 10 days since prior oral or parenteral anticoagulants except to maintain patency of pre-existing permanent indwelling IV catheters No concurrent aspirin No concurrent oral or parenteral anticoagulants except to maintain patency of pre-existing permanent indwelling IV catheters No other concurrent experimental or commercial agents or therapies for prostate cancer
Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>Autologous dendritic cells (DCs) are harvested and pulsed with prostatic acid phosphatase-sargramostim fusion protein to produce APC8015 (Provenge). Patients receive APC8015 IV over 30 minutes and bevacizumab IV over 30-60 minutes on day 1. Treatment repeats every 14 days for 3 courses. Patients continue to receive bevacizumab alone every 14 days in the absence of disease progression or unacceptable toxicity. | Biological: bevacizumab<br> <br> Biological: prostatic acid phosphatase-sargramostim fusion protein<br> <br> Biological: sipuleucel-T<br> <br> Biological: therapeutic autologous dendritic cells<br> <br> Procedure: in vitro-treated peripheral blood stem cell transplantation<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adenocarcinoma of the prostate, stage I prostate cancer, stage IIB prostate cancer, stage IIA prostate cancer, stage III prostate cancer, stage IV prostate cancer, recurrent prostate cancer