APC8015 and Bevacizumab in Treating Patients With Prostate Cancer

National Cancer Institute (NCI)

Status and phase

Completed

Phase 2

Conditions

Prostate Cancer

Treatments

Procedure: in vitro-treated peripheral blood stem cell transplantation

Biological: prostatic acid phosphatase-sargramostim fusion protein

Biological: sipuleucel-T

Biological: therapeutic autologous dendritic cells

Biological: bevacizumab

Study type

Interventional

Funder types

NIH

Identifiers

NCT00027599

NCI-2012-02427

NCI-2617

UCSF-01554

UCSF-0155-01

CDR0000069047 (Registry Identifier)

Details and patient eligibility

About

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.

Full description

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.

Enrollment

25 patients

Sex

Male

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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