Stage III Prostate CancerPhase 2NCT01385059
Axitinib Before Surgery in Treating Patients With High-Risk Prostate Cancer
A Phase 2 study testing axitinib, therapeutic conventional surgery and enzyme-linked immunosorbent assay in people with Stage III Prostate Cancer and Stage IV Prostate Cancer, run by City of Hope Medical Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Stage III Prostate Cancer, Stage IV Prostate Cancer
- What is being tested?
- axitinib, therapeutic conventional surgery and enzyme-linked immunosorbent assay
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Oct 2011to 9 Oct 2013
- 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
- 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
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- 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
- Life expectancy of >= 12 weeks
- No prior systemic therapy for prostate cancer
- No evidence of preexisting uncontrolled hypertension as documented by 2 consecutive blood pressure readings taken within 1 hour; the baseline systolic blood pressure readings must be =< 140 mm mercury (Hg), and the baseline diastolic blood pressure readings must be =< 90 mm Hg; patients whose hypertension is controlled by antihypertensive therapies are eligible
- Within 2 weeks of consent (and prior to initiating systemic therapy with axitinib if randomized to that arm), patients should visit with a radiation oncologist to discuss the option of radiation therapy (potentially with concomitant androgen deprivation therapy) for high-risk disease; if the patient has met with a radiation oncologist within 3 months of study enrollment to discuss the possibility of radiation therapy for localized prostate cancer, then this will suffice; patients do not have the right to refuse consultation; if this is the case, it must be documented by the treating physician in the medical record
- Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the trial prior to enrollment
Who cannot join
- 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
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- 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)
- Requirement of anticoagulant therapy with oral vitamin K antagonists; therapeutic use of low molecular weight heparin is allowed
- Active seizure disorder
- A serious uncontrolled medical disorder or active infection that would impair their ability to receive study treatment
- Any of the following within the 12 months prior to study drug administration: myocardial infarction, uncontrolled angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack and 6 months for deep vein thrombosis or pulmonary embolism
- Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness
- History of a malignancy (other than prostate cancer) except those treated with curative intent for skin cancer (other than melanoma), in situ breast or in situ cervical cancer, or those treated with curative intent for any other cancer with no evidence of disease for 2 years
- Dementia or significant altered mental status that would prohibit the understanding or rendering of informed consent and compliance with the requirements of this protocol
- Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the patient inappropriate for entry into this study
Trial locations and contacts
1 site in 1 country.
United States1 site
City of Hope Medical Center
Duarte, California, 91010
About this study
Official title: A Randomized, Phase II Study Assessing Axitinib as Pre-Surgical Therapy in Patients With High Risk Prostate Cancer
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
Read the detailed description
PRIMARY OBJECTIVES:
- To determine if axitinib modulates pre-metastatic niche density in patients with high-risk prostate cancer.
SECONDARY OBJECTIVES:
- 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.
- 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.
- Being tested
- axitinib, therapeutic conventional surgery, enzyme-linked immunosorbent assay, laboratory biomarker analysis
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
axitinibDrug
Also called AG-013736
Given PO
therapeutic conventional surgeryProcedure or surgery
Undergo prostatectomy and pelvic lymph node dissection
enzyme-linked immunosorbent assayOther
Also called ELISA
Correlative studies
laboratory biomarker analysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Procedure: therapeutic conventional surgery; Other: enzyme-linked immunosorbent assay; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: At the time of prostatectomy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jun 2011 (estimated)
- Study start28 Oct 2011
- Primary completion9 Oct 2013
- Study completion9 Oct 2013
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 Stage III Prostate CancerStudies of the same condition, open and under way.
- More trials run by City of Hope Medical CenterThe 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
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- City of Hope Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Sumanta Pal, Principal investigator, City of Hope Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01385059
- Sponsor's protocol ID
- 10151
- Other IDs
- NCI-2011-01105
- Status last verified
- Feb 2023
- First submitted
- 24 Jun 2011
- Last updated
- 7 Mar 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 26450920
Study at a glance
From the registry record, last updated by the sponsor on 7 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Phase II Study Assessing Axitinib as Pre-Surgical Therapy in Patients With High Risk Prostate Cancer
- ClinicalTrials.gov ID
- NCT01385059
- Acronym / sponsor ID
- 10151
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- City of Hope Medical CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 28 Oct 2011 (actual)
- Primary completion
- 9 Oct 2013 (actual)
- Study completion
- 9 Oct 2013 (actual)
- First posted
- 29 Jun 2011 (estimated)
- Results
- Posted 7 Mar 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- To determine if axitinib modulates pre-metastatic niche density in patients with high-risk prostate cancer.
SECONDARY OBJECTIVES:
- 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.
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I (neoadjuvant enzyme inhibitor and prostatectomy) | Experimental | Drug: axitinib, Procedure: therapeutic conventional surgery, Other: enzyme-linked immunosorbent assay, Other: laboratory biomarker analysisPatients 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. |
| Arm II (surgery) | Active comparator | Procedure: therapeutic conventional surgery, Other: enzyme-linked immunosorbent assay, Other: laboratory biomarker analysisPatients undergo prostatectomy and pelvic lymph node dissection at 5-6 weeks after biopsy confirmation of prostate cancer. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Histologically confirmed diagnosis of prostate cancer
- High-risk prostate cancer as defined by 1 of the 3 following criteria:
- 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
Key exclusion criteria (23 listed)
- 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
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 |
|---|---|---|
| axitinibAlso: AG-013736Given PO | Drug | Arm I (neoadjuvant enzyme inhibitor and prostatectomy) |
| therapeutic conventional surgeryUndergo prostatectomy and pelvic lymph node dissection | Procedure or surgery | Arm I (neoadjuvant enzyme inhibitor and prostatectomy), Arm II (surgery) |
| enzyme-linked immunosorbent assayAlso: ELISACorrelative studies | Other | Arm I (neoadjuvant enzyme inhibitor and prostatectomy), Arm II (surgery) |
| laboratory biomarker analysisCorrelative studies | Other | Arm I (neoadjuvant enzyme inhibitor and prostatectomy), Arm II (surgery) |
Primary outcome
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Mar 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 26450920Pal 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.
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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.
Sumanta Pal principal investigator
City of Hope Medical Center
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 axitinib, therapeutic conventional surgery and enzyme-linked immunosorbent assay in people with Stage III Prostate Cancer and Stage IV Prostate Cancer, run by City of Hope Medical Center 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 20 inclusion and 23 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 7 Mar 2023. 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. 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 7 Mar 2023). 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?
Pre-metastatic Niche Density (time frame: At the time of prostatectomy). 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 NCT01385059, 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 7 Mar 2023.