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Rituximab Neoadjuvant Therapy in Patients With Prostate Cancer Scheduled to Undergo Radical Prostatectomy

Primary Purpose

Prostate Cancer

Status
Unknown status
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
rituximab
Sponsored by
Stephen Howell, M.D.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Prostate Cancer focused on measuring Prostate, Cancer, Castration-resistant, Rituximab, neoadjuvant, Rituxan

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

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).

Sites / Locations

  • Moores UCSD Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

rituximab

Arm Description

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).

Outcomes

Primary Outcome Measures

Histologic response rate after one cycle of rituximab

Secondary Outcome Measures

Change in prostate-specific antigen (PSA)
Change in peripheral blood B cell number
Change in serum CXCL13 level

Full Information

First Posted
March 1, 2013
Last Updated
May 17, 2017
Sponsor
Stephen Howell, M.D.
Collaborators
Genentech, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT01804712
Brief Title
Rituximab Neoadjuvant Therapy in Patients With Prostate Cancer Scheduled to Undergo Radical Prostatectomy
Official Title
A Pilot Study of Rituximab Neoadjuvant Therapy in Patients With High Risk Prostate Cancer Scheduled to Undergo Radical Prostatectomy
Study Type
Interventional

2. Study Status

Record Verification Date
May 2017
Overall Recruitment Status
Unknown status
Study Start Date
July 2013 (undefined)
Primary Completion Date
April 2018 (Anticipated)
Study Completion Date
April 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Stephen Howell, M.D.
Collaborators
Genentech, Inc.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Cancer
Keywords
Prostate, Cancer, Castration-resistant, Rituximab, neoadjuvant, Rituxan

7. Study Design

Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
18 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
rituximab
Arm Type
Experimental
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
rituximab
Other Intervention Name(s)
Rituxan
Intervention Description
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).
Primary Outcome Measure Information:
Title
Histologic response rate after one cycle of rituximab
Time Frame
1 treatment cycle (28 days)
Secondary Outcome Measure Information:
Title
Change in prostate-specific antigen (PSA)
Time Frame
from Day 1 to Day 29
Title
Change in peripheral blood B cell number
Time Frame
from Day 1 to Day 29
Title
Change in serum CXCL13 level
Time Frame
from Day 1 to Day 29

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stephen Howell, MD
Organizational Affiliation
University of California Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Moores UCSD Cancer Center
City
La Jolla
State/Province
California
ZIP/Postal Code
92093-0698
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
32466781
Citation
Ryan ST, Zhang J, Burner DN, Liss M, Pittman E, Muldong M, Shabaik A, Woo J, Basler N, Cunha J, Shalapour S, Estrada MV, Karin M, Messer K, Howell S, Kane CJ, Jamieson CAM. Neoadjuvant rituximab modulates the tumor immune environment in patients with high risk prostate cancer. J Transl Med. 2020 May 28;18(1):214. doi: 10.1186/s12967-020-02370-4.
Results Reference
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Rituximab Neoadjuvant Therapy in Patients With Prostate Cancer Scheduled to Undergo Radical Prostatectomy

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