Prostate Cancer
Conditions
Keywords
Prostate, Cancer, Castration-resistant, Rituximab, neoadjuvant, Rituxan
Brief summary
There is now substantial evidence that B cells are recruited into prostate cancers by CXCL13 released by the tumor cells. B cells release lymphotoxin which drives malignant cell proliferation through the NFkB pathway. This is a pilot trial in 18 patients to determine whether depletion of B cells by rituximab will result in a decrease in the extent of B cell infiltration of the prostatic cancer. The extent of infiltration in the diagnostic biopsy will be compared to that in the prostatectomy samples following administration of 4 weekly doses of rituximab.
Detailed description
This is an open label, single institution, pilot study of rituximab neoadjuvant therapy in patients with high risk prostate cancer scheduled to undergo radical prostatectomy. Prior to prostatectomy, patients will receive one treatment cycle (28 days) of rituximab 375 mg/m2 intravenously once weekly. Patients will be scheduled to undergo radical prostatectomy within two weeks of completing study treatment. Tissue from prostatectomy will be used for immunohistochemistry (IHC) staining of pharmacodynamic markers.
Interventions
DRUGrituximab
Rituximab will be administered intravenously at a dose of 375 mg/m2 of body surface area once per week for 4 weeks (Days 1, 8, 15, and 22 of a 28-day cycle).
Sponsors
Christopher Kane
Genentech, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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 (Appendix A). * Males aged ≥ 18 years. * Adequate organ function as defined below measured within 21 days of study entry: * Hematology: * Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L * Platelet count ≥ 100 x 109/L * Hemoglobin ≥ 9.0 g/dL * White blood cell (WBC) count ≥ 3.0 x 109/L * Biochemistry: * Aspartate aminotransferase/serum glutamic-oxaloacetic transaminase (AST/SGOT) and alanine transaminase/serum glutamate pyruvate transaminase (ALT/SGPT) ≤ 2 x institution's upper limit of normal (ULN) * Total bilirubin \<1.5 times ULN * Serum creatinine and blood urea nitrogen (BUN)\<1.5 times ULN * Na, K Cl, carbon dioxide (CO2), Ca, phosphate (PO4) within institutional limits * Available prostate biopsy specimen which is evaluable for B lymphocyte count.
Exclusion criteria
* Received prior treatment for prostatic adenocarcinoma including prior surgery (excluding TURP), radiation therapy, or chemotherapy. * Current or past use of investigational agents within 4 weeks of study enrollment. * Evidence of metastatic disease on cross sectional imaging or bone scan. * History of hepatitis B or C, hepatitis immunodeficiency virus (HIV), tuberculosis or a chronic infection of any type. * Positive test results for chronic hepatitis B infection (defined as positive HBsAg serology). * Positive test results for hepatitis C (hepatitis C virus \[HCV\] antibody serology testing).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| B-cell Density Stained Area | 1 treatment cycle (28 days) | Immunohistochemical staining of serial prostatectomy sections to measure the density of CD20+ B-cells as stained area (mm\^2/mm\^2) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Prostate-specific Antigen (PSA) | from Day 1 to Day 29 | Prostate-specific antigen (PSA) |
| Change in Tumor B-cell Stained Area | from Day 1 to Day 29 | Immunohistochemical staining of serial prostatectomy sections to measure the density of CD20+ B-cells as stained area (mm\^2/mm\^2) |
| Tumor CD3+ T-cell Stained Area | from Day 1 to Day 29 | Immunohistochemical staining of serial prostatectomy sections to measure the density of CD3+ T-cells as stained area (mm\^2/mm\^2) |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORStephen Howell, MD
University of California Medical Center
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 62.3 Years STANDARD_DEVIATION 5.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| PSA at dx | 7.7 ng/mL STANDARD_DEVIATION 4.7 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 7 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 8 |
| other Total, other adverse events | 4 / 8 |
| serious Total, serious adverse events | 1 / 8 |
Outcome results
None listed