Adenocarcinoma of the ProstatePhase 2NCT01832259
A Study of VEGF Tyrosine Kinase Inhibitor (Pazopanib) in Men With High-Risk Prostate Cancer Followed by Radical Prostatectomy and Pelvic Lymph Node Dissection
A Phase 2 study testing Pazopanib in people with Adenocarcinoma of the Prostate, run by University of Utah at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Adenocarcinoma of the Prostate
- What is being tested?
- Pazopanib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2013to 9 Aug 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
- Note: Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry. Following antihypertensive medication initiation or adjustment, blood pressure (BP) must be re-assessed three times at approximately 2-minute intervals. At least 24 hours must have elapsed between anti-hypertensive medication initiation or adjustment and Blood Pressure measurement. These three values should be averaged to obtain the mean diastolic blood pressure (DBP) and the mean systolic blood pressure (SBP). The mean SBP / DBP ratio must be <140/90 mm Hg (OR 150/90 mm Hg, if this criterion is approved by the Huntsman Cancer Institute (HCI) Data Safety and Monitoring Committee (DSMC) Chair or Co-chair) in order for a subject to be eligible for the study (see protocol for details on Blood Pressure control and re-assessment prior to study enrollment).
- History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months.
- Major surgery or trauma within 28 days prior to first dose of investigational product and/or presence of any non-healing wound, fracture, or ulcer (procedures such as catheter placement not considered to be major surgery).
- Evidence of active bleeding or bleeding diathesis.
- Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels that increase the risk of pulmonary hemorrhage Note: Lesions infiltrating major pulmonary vessels (contiguous tumour and vessels) are excluded; however, the presence of a tumor that is touching, but not infiltrating (abutting) the vessels is acceptable (CT (computed tomography) with contrast is strongly recommended to evaluate such lesions).
- Large protruding endobronchial lesions in the main or lobar bronchi are excluded; however, endobronchial lesions in the segmented bronchi are allowed.
- Lesions extensively infiltrating the main or lobar bronchi are excluded; however, minor infiltrations in the wall of the bronchi are allowed.
- Recent hemoptysis (=> ½ teaspoon of red blood within 8 weeks before first dose of study drug).
- Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures.
- Unable or unwilling to discontinue use of prohibited medications listed in the protocol for at least 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of study drug and for the duration of the study.
- Treatment with any of the following anti-cancer therapies:
- radiation therapy, chemotherapy, immunotherapy, biologic therapy, investigational therapy
- surgery or tumor embolization within 14 days prior to the first dose of pazopanib OR hormonal therapy within 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of Pazopanib
- Administration of any non-oncologic investigational drug within 30 days or 5 half lives whichever is longer prior to receiving the first
- Any ongoing toxicity from prior hormonal therapy that is >Grade 1 and/or that is progressing in severity.
Trial locations and contacts
1 site in 1 country.
United States1 site
Huntsman Cancer Institute
Salt Lake City, Utah, 84112
About this study
Official title: A Neoadjuvant, Randomized, Phase II Study of Vascular Endothelial Growth Factor (VEGF) Tyrosine Kinase Inhibitor (Pazopanib) in Men With High-Risk Prostate Cancer Followed by Radical Prostatectomy and Pelvic Lymph Node Dissection
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
- Being tested
- Pazopanib, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PazopanibDrug
Pazopanib, 800 mg, orally daily for 28 days prior to radical prostatectomy.
PlaceboOther
Placebo tablet orally, daily for 28 days prior to radical prostatectomy.
| Study group | Role | What they receive |
|---|---|---|
| Placebo arm | Placebo comparator | Participants receiving placebo Receives: Other: Placebo |
| Pazopanib arm | Experimental | Participants receiving Pazopanib Receives: Drug: Pazopanib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 1 month
Secondary outcomes (2)
Participants Experiencing Adverse Events
Adverse events were assessed using the Common Terminology for Adverse Events (CTCAE) version 4. Each event was assigned a grade (1-5), with lower grades indicating milder events. All adverse events were recorded, regardless of attribution to study treatment. For a full listing of Adverse Events, please see the Adverse Events section of the Results for this study.
Measured: From first dose of study treatment to one month post-prostatectomy (approximately 2 months)
Biochemical Recurrence Progression Free Survival Rate
Following prostatectomy, patients' Prostate Specific Antigen (PSA) lab values were collected for up to two years. Biochemical recurrence was defined as the first PSA lab value of greater than or equal to 0.2 ng/mL following prostatectomy. Biochemical recurrence progression free survival rate was defined as the percent chance of 1 year survival with no biochemical recurrence.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Apr 2013 (estimated)
- Study startAug 2013
- Primary completion7 Feb 2017
- Study completion9 Aug 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Adenocarcinoma of the ProstateStudies of the same condition, open and under way.
- More trials run by University of UtahThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Utah
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis
- Responsible party
- Sponsor
- Investigators
- Neeraj Agarwal, MD, Principal investigator, Huntsman Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01832259
- Sponsor's protocol ID
- HCI63129
- Status last verified
- Dec 2018
- First submitted
- 21 Mar 2013
- Last updated
- 12 Dec 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 30575560
Study at a glance
From the registry record, last updated by the sponsor on 12 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Neoadjuvant, Randomized, Phase II Study of Vascular Endothelial Growth Factor (VEGF) Tyrosine Kinase Inhibitor (Pazopanib) in Men With High-Risk Prostate Cancer Followed by Radical Prostatectomy and Pelvic Lymph Node Dissection
- ClinicalTrials.gov ID
- NCT01832259
- Acronym / sponsor ID
- HCI63129
- Conditions
- Adenocarcinoma of the Prostate
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- University of UtahUniversity, hospital or other
- Collaborators
- Novartis
- Study start
- Aug 2013
- Primary completion
- 7 Feb 2017 (actual)
- Study completion
- 9 Aug 2018 (actual)
- First posted
- 16 Apr 2013 (estimated)
- Results
- Posted 12 Jun 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo arm | Placebo comparator | Other: PlaceboParticipants receiving placebo |
| Pazopanib arm | Experimental | Drug: PazopanibParticipants receiving Pazopanib |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 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.
Key exclusion criteria (30 listed)
- 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:
- Corrected QT interval (QTc) > 480 msecs Note: Correction method should be reported
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PazopanibPazopanib, 800 mg, orally daily for 28 days prior to radical prostatectomy. | Drug | Pazopanib arm |
| PlaceboPlacebo tablet orally, daily for 28 days prior to radical prostatectomy. | Other | Placebo arm |
Primary outcome
Number of Vascular Endothelial Growth Factor Receptor 1 (VEGFR1)-Positive Clusters
Time frame: 1 month
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.
2 secondary outcomes
Participants Experiencing Adverse Events
Time frame: From first dose of study treatment to one month post-prostatectomy (approximately 2 months)
Biochemical Recurrence Progression Free Survival Rate
Time frame: 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Dec 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30575560Maughan 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Neeraj Agarwal, MD principal investigator
Huntsman Cancer Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pazopanib in people with Adenocarcinoma of the Prostate, run by University of Utah at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Jun 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Vascular Endothelial Growth Factor Receptor 1 (VEGFR1)-Positive Clusters (time frame: 1 month). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01832259, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Dec 2018.