Rituximab in Treating Patients with High-Risk Prostate Cancer Undergoing Surgery
This early phase I trial studies rituximab in treating patients with high-risk prostate cancer undergoing surgery. Monoclonal antibodies, such as rituximab, may block tumor growth in different ways by targeting certain cells.
Inclusion Criteria
- Ability to understand and provide written informed consent
- Patient has EITHER: * A Kattan nomogram predicted probability of being disease free 5 years after surgery of < 60%, OR * A Gleason sum >= 8
- Indicated for radical prostatectomy * Note: candidates for radical prostatectomy are still eligible even if they have a history of deep venous thrombosis, pulmonary embolism, and/or cerebrovascular accident or currently requiring systemic anticoagulation
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
- Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
- Platelet count >= 100 x 10^9/L
- Hemoglobin >= 9.0 g/dL
- White blood cell (WBC) count >= 3.0 x 10^9/L
- Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/serum glutamate pyruvate transaminase (SGPT) =< 2 x institution’s upper limit of normal (ULN)
- Total bilirubin < 1.5 times ULN
- Serum creatinine < 1.5 times ULN
- Blood urea nitrogen (BUN) < 1.5 times ULN
- Sodium (Na), potassium chloride (K Cl), carbon dioxide (CO2), calcium (Ca), phosphate (PO4) within institutional limits
Exclusion Criteria
- Received prior treatment for prostatic adenocarcinoma including prior surgery (excluding transurethral resection of the prostate [TURP]), radiation therapy, or chemotherapy
- Current or past use of investigational agents within 4 weeks of study enrollment
- Use of erectile dysfunction drugs (e.g., Cialis, Viagra) within 14 days prior to treatment or during study
- Evidence of metastatic disease on cross sectional imaging or bone scan
- Receipt of a live vaccine within 4 weeks prior to rituximab administration
- History of hepatitis B or C, human immunodeficiency virus (HIV), tuberculosis or a chronic infection of any type
- Positive test results for chronic hepatitis B infection (defined as positive hepatitis B surface antigen [HBsAg] serology)
- Positive test results for hepatitis C (hepatitis C virus [HCV] antibody serology testing)
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT01804712.
PRIMARY OBJECTIVES:
I. To determine the histologic response rate in patients with high risk prostate cancer receiving one treatment cycle of neoadjuvant rituximab prior to radical prostatectomy, defined as an extent of B cell infiltration within the tumor region of the prostatectomy specimen of =< the 18.2 percentile of the B cell content from 27 historical control samples.
SECONDARY OBJECTIVES:
I. To determine the effectiveness of neoadjuvant rituximab in the treatment of prostate cancer as evaluated by the serum prostate-specific antigen (PSA).
II. To determine the effect of neoadjuvant rituximab on the serum chemokine (C-X-C motif) ligand 13 (CXCL13) concentration.
III. To determine the effect of neoadjuvant rituximab on peripheral blood B lymphocyte count.
IV. To assess the safety and tolerability of neoadjuvant rituximab.
V. To explore the impact of neoadjuvant rituximab on immunohistochemical staining profiles of primary tumors including expression of: I-kappa-B kinase alpha (IKK-alpha); BMI1 polycomb ring finger oncogene (BMI1); ubiquitinated histone 2A; B cell marker cluster of differentiation (CD)20; T cell markers CD3, CD4, and CD8; macrophage markers CD68 and CD11b; alpha-smooth muscle actin (alpha-SMA); CXCL13; lymphotoxin alpha (LT-alpha) and lymphotoxin beta (LT-beta), and lymphotoxin beta receptor (LT-beta-R).
VI. To understand the long term impact of neoadjuvant rituximab in the treatment of prostate cancer on biochemical relapse based on PSA levels collected during standard of care follow-up.
OUTLINE:
Patients receive rituximab intravenously (IV) on days 1, 8, 15, and 22. Treatment continues in the absence of disease progression or unacceptable toxicity. Within 14 days after the last dose of rituximab, patients undergo radical prostatectomy.
After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 1 year.
Trial PhasePhase O
Trial Typetreatment
Lead OrganizationUC San Diego Medical Center - Hillcrest
Principal InvestigatorStephen B Howell
- Primary ID121451
- Secondary IDsNCI-2013-01403, UCSD 121451
- ClinicalTrials.gov IDNCT01804712