A Randomized, Phase II Study Assessing Axitinib as Pre-Surgical Therapy in Patients With High Risk Prostate Cancer
Overview
- Phase
- Phase 2
- Intervention
- laboratory biomarker analysis
- Conditions
- Stage III Prostate Cancer
- Sponsor
- City of Hope Medical Center
- Enrollment
- 11
- Locations
- 1
- Primary Endpoint
- Pre-metastatic Niche Density
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
This randomized phase II trial studies how well axitinib works in treating patients with high-risk prostate cancer before undergoing surgery. Axitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving axitinib before surgery may make the tumor smaller and reduce the amount of normal cells that have to be removed
Detailed Description
PRIMARY OBJECTIVES: I. To determine if axitinib modulates pre-metastatic niche density in patients with high-risk prostate cancer. SECONDARY OBJECTIVES: I. To determine if pre-metastatic niche density in regional lymph nodes (LNs) is associated with progression-free survival (PFS). II. To determine if therapy with axitinib prolongs time to biochemical recurrence. III. To determine if phosphorylated form of signal transducer and activator of transcription (pSTAT)3 in tumor tissue is associated with biochemical recurrence. IV. To determine if myeloid derived suppressor cell (MDSC) recruitment in tumor tissue is associated with biochemical recurrence. V. To determine if lysyl oxidase (LOX) expression in tumor tissue is associated with biochemical recurrence. VI. To evaluate time to metastatic recurrence. VII. To determine the rate of erectile dysfunction and urinary incontinence (grade \>= 3 for both) in the setting of preoperative axitinib therapy. VIII. To evaluate changes in blood-based biomarkers (pSTAT3 and selected angiogenic factors) from baseline to the time of prostatectomy. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive axitinib orally (PO) twice daily (BID) on days 1-28. Patients then undergo prostatectomy and pelvic lymph node dissection. Treatment continues in the absence of disease progression or unacceptable toxicity. ARM II: Patients undergo prostatectomy and pelvic lymph node dissection at 5-6 weeks after biopsy confirmation of prostate cancer. After completion of study treatment, patients are followed up periodically.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically confirmed diagnosis of prostate cancer
- •High-risk prostate cancer as defined by 1 of the 3 following criteria:
- •Baseline prostate specific antigen (PSA) \> 20
- •Clinical stage \>= T3a and
- •Gleason score 8-9
- •Subjects must be appropriate candidates for prostatectomy and pelvic lymph node dissection, as deemed by multidisciplinary tumor team; subjects must provide informed consent to these procedures prior to initiating study treatment
- •Subjects must provide written informed consent prior to performance of study-specific procedures or assessments, and must be willing to comply with treatment and follow-up; procedures conducted as part of the subject's routine clinical management (e.g., blood count, imaging study) and obtained prior to signing of informed consent may be utilized for screening or baseline purposes provided these procedures are conducted as specified in the protocol
- •Absolute neutrophil count (ANC) \>= 1500 cells/mm\^3
- •Platelets \>= 100,000 cells/mm\^3
- •Hemoglobin \>= 9.0 g/dL
Exclusion Criteria
- •Prior systemic therapy for prostate cancer (including by not limited to endocrine therapy; i.e., LHRH analogues, antiandrogens, etc.)
- •Evidence of metastatic disease
- •Prior radiation therapy for prostate cancer
- •Known history of allergic reactions to axitinib or other VEGF-TKIs
- •Presence of serious or uncontrollable infection
- •Major surgery \<4 weeks of starting the study treatment
- •Gastrointestinal abnormalities including:
- •Inability to take oral medication
- •Requirement for intravenous alimentation
- •Prior surgical procedures affecting absorption including total gastric resection
Arms & Interventions
Arm II (surgery)
Patients undergo prostatectomy and pelvic lymph node dissection at 5-6 weeks after biopsy confirmation of prostate cancer.
Intervention: laboratory biomarker analysis
Arm I (neoadjuvant enzyme inhibitor and prostatectomy)
Patients receive axitinib PO BID on days 1-28. Patients then undergo prostatectomy and pelvic lymph node dissection. Treatment continues in the absence of disease progression or unacceptable toxicity.
Intervention: axitinib
Arm I (neoadjuvant enzyme inhibitor and prostatectomy)
Patients receive axitinib PO BID on days 1-28. Patients then undergo prostatectomy and pelvic lymph node dissection. Treatment continues in the absence of disease progression or unacceptable toxicity.
Intervention: therapeutic conventional surgery
Arm I (neoadjuvant enzyme inhibitor and prostatectomy)
Patients receive axitinib PO BID on days 1-28. Patients then undergo prostatectomy and pelvic lymph node dissection. Treatment continues in the absence of disease progression or unacceptable toxicity.
Intervention: enzyme-linked immunosorbent assay
Arm I (neoadjuvant enzyme inhibitor and prostatectomy)
Patients receive axitinib PO BID on days 1-28. Patients then undergo prostatectomy and pelvic lymph node dissection. Treatment continues in the absence of disease progression or unacceptable toxicity.
Intervention: laboratory biomarker analysis
Arm II (surgery)
Patients undergo prostatectomy and pelvic lymph node dissection at 5-6 weeks after biopsy confirmation of prostate cancer.
Intervention: therapeutic conventional surgery
Arm II (surgery)
Patients undergo prostatectomy and pelvic lymph node dissection at 5-6 weeks after biopsy confirmation of prostate cancer.
Intervention: enzyme-linked immunosorbent assay
Outcomes
Primary Outcomes
Pre-metastatic Niche Density
Time Frame: At the time of prostatectomy
The niche density is defined as the average number of VEGF receptor 1 (VEGFR1) clusters in 8 distinct 40X microscopic fields in the regional lymph nodes of patients. We will use a two sample student's T-test to compare the primary endpoint of pre-metastatic niche density in the patients treated with axitinib, as compared to the pre-metastatic niche density in the patients enrolled on the control arm.