Axitinib Before Surgery in Treating Patients With High-Risk Prostate Cancer

NCT01385059 | Completed Phase 2 Results DMC

• 2 other identifiers: 10151NCI-2011-01105
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

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

Conditions

Stage III Prostate Cancer; Stage IV Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• Pre-metastatic Niche Density

  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.

  At the time of prostatectomy

Study Arms (2)

Arm I (neoadjuvant enzyme inhibitor and prostatectomy)

EXPERIMENTAL

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.

Drug: axitinib; Procedure: therapeutic conventional surgery; Other: enzyme-linked immunosorbent assay; Other: laboratory biomarker analysis

Arm II (surgery)

ACTIVE COMPARATOR

Patients undergo prostatectomy and pelvic lymph node dissection at 5-6 weeks after biopsy confirmation of prostate cancer.

Procedure: therapeutic conventional surgery; Other: enzyme-linked immunosorbent assay; Other: laboratory biomarker analysis

Interventions

axitinib DRUG

Given PO

Also known as: AG-013736

Arm I (neoadjuvant enzyme inhibitor and prostatectomy)

therapeutic conventional surgery PROCEDURE

Undergo prostatectomy and pelvic lymph node dissection

Arm I (neoadjuvant enzyme inhibitor and prostatectomy); Arm II (surgery)

enzyme-linked immunosorbent assay OTHER

Correlative studies

Also known as: ELISA

Arm I (neoadjuvant enzyme inhibitor and prostatectomy); Arm II (surgery)

laboratory biomarker analysis OTHER

Correlative studies

Arm I (neoadjuvant enzyme inhibitor and prostatectomy); Arm II (surgery)

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 X upper limit of normal (ULN)
• Total bilirubin =\< 1.5 X ULN
• Serum creatinine =\< 1.5 X ULN or calculated creatinine clearance \>= 60 mL/min
• Urinary protein \< 2+ by urine analysis (UA); if UA is \>= 2+ for protein then a 24-hour urine collection can be done and the patient may enter only if urinary protein is \< 2 g per 24 hours
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

You may not qualify if:

• 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
• Treatment for active peptic ulcer disease in the past 6 months
• Active gastrointestinal bleeding, unrelated to cancer, as evidenced by hematemesis, hematochezia or melena in the past 3 months without evidence of resolution documented by endoscopy or colonoscopy
• Malabsorption syndromes
• Current use or anticipated need for treatment with drugs that are known potent cytochrome P450 3A4 (CYP3A4) inhibitors (ie, grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole, erythromycin, telithromycin, clarithromycin, indinavir, saquinavir, ritonavir, nelfinavir, lopinavir, atazanavir, amprenavir, fosamprenavir and delavirdine)
• Current use or anticipated need for treatment with drugs that are known CYP3A4 or cytochrome P450 1A2 (CYP1A2) inducers (ie, carbamazepine, dexamethasone, felbamate, omeprazole, phenobarbital, phenytoin, amobarbital, nevirapine, primidone, rifabutin, rifampin, and St. John's wort)

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

Related Publications (1)

• Pal SK, Vuong W, Zhang W, Deng J, Liu X, Carmichael C, Ruel N, Pinnamaneni M, Twardowski P, Lau C, Yu H, Figlin RA, Agarwal N, Jones JO. Clinical and Translational Assessment of VEGFR1 as a Mediator of the Premetastatic Niche in High-Risk Localized Prostate Cancer. Mol Cancer Ther. 2015 Dec;14(12):2896-900. doi: 10.1158/1535-7163.MCT-15-0367. Epub 2015 Oct 8.

  PMID: 26450920 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Axitinib; Enzyme-Linked Immunosorbent Assay

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Indazoles; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Immunoenzyme Techniques; Immunoassay; Immunologic Techniques; Investigative Techniques; Immunosorbent Techniques; Immunohistochemistry; Molecular Probe Techniques

Results Point of Contact

• Title: Dr. Sumanta Kumar Pal
• Organization: City of Hope Medical Center

SPal@coh.org

626-359-8111

Study Officials

• Sumanta Pal

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 24, 2011
• First Posted: June 29, 2011
• Study Start: October 28, 2011
• Primary Completion: October 9, 2013
• Study Completion: October 9, 2013
• Last Updated: March 7, 2023
• Results First Posted: March 7, 2023

Record last verified: 2023-02

Locations

US (1)