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

Stephen Howell, M.D.

Status and phase: Unknown; Early Phase 1

Conditions: Prostate Cancer

Treatments: Drug: rituximab

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01804712

121451

Details and patient eligibility

About

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.

Full 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.

Enrollment: 18 estimated patients

Sex: Male

Ages: 18+ years old

Volunteers: No 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).

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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18 participants in 1 patient group

rituximab

Experimental group

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).

Treatment:

Drug: rituximab