A Study of VEGF Tyrosine Kinase Inhibitor (Pazopanib) in Men With High-Risk Prostate Cancer Followed by Radical Prostatectomy and Pelvic Lymph Node Dissection

NCT01832259 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: HCI63129
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The area around a tumor ("pre-metastatic niche") may be an area to which cancer cells are attracted. The study doctor will take blood and tumor samples to look for certain features linked with response to treatment so that they can predict which future patients may benefit from this therapy. The purpose of this study is to see if the drug pazopanib can be used to reduce the amount of pre-metastatic niche in the patient's lymph nodes (a common site for prostate cancer to spread). Down the line, this may help to prevent prostate cancer from coming back after surgery.

Conditions

Adenocarcinoma of the Prostate

Outcome Measures

Primary Outcomes (1)

• Number of Vascular Endothelial Growth Factor Receptor 1 (VEGFR1)-Positive Clusters

  Patients with high-risk, localized prostate cancer were treated with 28 days of Pazopanib or placebo, after which they underwent radical prostatectomy. During prostatectomy, benign pelvic lymph node tissue was collected and subsequently analyzed for the average number of VEGFR1-positive clusters in 8 distinct 40x microscopic fields as an indicator of pre-metastatic niche formation.

  1 month

Secondary Outcomes (2)

• Participants Experiencing Adverse Events

  From first dose of study treatment to one month post-prostatectomy (approximately 2 months)

• Biochemical Recurrence Progression Free Survival Rate

  2 years

Study Arms (2)

Placebo arm

PLACEBO COMPARATOR

Participants receiving placebo

Other: Placebo

Pazopanib arm

EXPERIMENTAL

Participants receiving Pazopanib

Drug: Pazopanib

Interventions

Pazopanib DRUG

Pazopanib, 800 mg, orally daily for 28 days prior to radical prostatectomy.

Pazopanib arm

Placebo OTHER

Placebo tablet orally, daily for 28 days prior to radical prostatectomy.

Placebo arm

Eligibility Criteria

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

You may qualify if:

• Men ≥ 18 years of age
• Histological documentation of adenocarcinoma of the prostate, with available biopsy pathology. Biopsy material must be available for pathologic review.
• All patients must meet one or more of the following disease features: clinical stage greater than or equal to T3; Primary Gleason score of 4 OR Gleason score of 8, 9 or 10; serum prostate-specific antigen (PSA) ≥ 20 ng/mL; Prostate MRI findings consistent with T3 disease; Any clinical stage and PSA (prostate-specific antigen) \>10 and Gleason score 7; A Kattan nomogram predicted probability of being free from biochemical progression at 5 years after surgery of \< 60%.
• Patients must have a PSA (prostate-specific antigen) ≥ 2 ng/mL at the time of diagnosis of prostate cancer or later.
• No prior radiation or chemotherapy for prostate cancer treatment.
• Scheduled for radical prostatectomy surgery.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
• Patients may have been treated with up to 4 months of androgen deprivation therapy.
• No clinical evidence of metastatic prostate cancer, or enlarged pelvic lymph nodes in the imaging studies.
• Resected lymph nodes must be provided for all subjects for biomarker analysis immediately (same day) after surgery (radical prostatectomy).
• Adequate organ system function as defined by study Protocol
• Subjects may not have had a transfusion within 7 days of screening assessment.
• Concomitant elevations in bilirubin and aspartate aminotransferase (AST)/alanine aminotransferase (ALT) above 1.0 x upper limit of normal (ULN) are not permitted.
• If urine protein count (UPC) =\>1, then a 24-hour urine protein must be assessed. Subjects must have a 24-hour urine protein value \<1 to be eligible.
• Subjects must provide written informed consent within one month prior to performance of study-specific procedures or assessments and must be willing to comply with treatment and follow up.

You may not qualify if:

• Clinical evidence of metastatic prostate cancer.
• Prior malignancy. No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for 5 years.
• Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to: Active peptic ulcer disease Known intraluminal metastatic lesion/s with risk of bleeding Inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease), or other gastrointestinal conditions with increased risk of perforation History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to beginning study treatment.
• Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product including, but not limited to:
• Malabsorption syndrome or
• Major resection of the stomach or small bowel.
• Corrected QT interval (QTc) \> 480 msecs Note: Correction method should be reported
• History of any one or more of the following cardiovascular conditions within the past 6 months:
• Cardiac angioplasty or stenting
• Myocardial infarction
• Unstable angina
• Coronary artery bypass graft surgery
• Symptomatic peripheral vascular disease
• Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA)
• No evidence of preexisting uncontrolled hypertension. If the patient has a history of elevated blood pressure at baseline then they must have controlled hypertension documented and confirmed by 2 consecutive blood pressure readings taken within 1 hour. The baseline systolic blood pressure readings must be =\<140 mm Hg, and the baseline diastolic blood pressure readings must be =\<90 mm Hg.

Sponsors & Collaborators

• University of Utah: lead
• Novartis: collaborator

Study Sites (1)

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

Related Publications (1)

• Maughan BL, Pal SK, Gill D, Boucher K, Martin C, Salgia M, Nussenzveig R, Liu T, Hawks JL, Batten J, Nachaegari G, Stephenson R, Lowrance W, Jones J, Dechet C, Agarwal N. Modulation of Premetastatic Niche by the Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitor Pazopanib in Localized High-Risk Prostate Cancer Followed by Radical Prostatectomy: A Phase II Randomized Trial. Oncologist. 2018 Dec;23(12):1413-e151. doi: 10.1634/theoncologist.2018-0652. Epub 2018 Nov 1.

  PMID: 30575560 DERIVED

MeSH Terms

Interventions

pazopanib

Results Point of Contact

• Title: Josiah Lyn Hawks
• Organization: Huntsman Cancer Institute / University of Utah

Josiah.Hawks@hci.utah.edu

801-585-0601

Study Officials

• Neeraj Agarwal, MD

  Huntsman Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 21, 2013
• First Posted: April 16, 2013
• Study Start: August 1, 2013
• Primary Completion: February 7, 2017
• Study Completion: August 9, 2018
• Last Updated: December 12, 2018
• Results First Posted: June 12, 2018

Record last verified: 2018-12

Locations

US (1)