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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
City of Hope Medical Center
ClinicalTrials.gov Identifier:
NCT01385059
First received: June 24, 2011
Last updated: July 17, 2014
Last verified: July 2014
  Purpose

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


Condition Intervention Phase
Stage III Prostate Cancer
Stage IV Prostate Cancer
Drug: axitinib
Procedure: therapeutic conventional surgery
Other: enzyme-linked immunosorbent assay
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized, Phase II Study Assessing Axitinib as Pre-Surgical Therapy in Patients With High Risk Prostate Cancer

Resource links provided by NLM:


Further study details as provided by City of Hope Medical Center:

Primary Outcome Measures:
  • Changes in pre-metastatic niche density, as defined by the average number of VEGF receptor 1 (VEGFR1) clusters in 8 distinct 40X microscopic fields [ Time Frame: Week 9 post treatment ] [ Designated as safety issue: No ]
    We will use a two sample student's T-test to compare pre-metastatic niche density in the regional lymph nodes of patients treated with axitinib, as compared to the pre-metastatic niche density in the lymph nodes of patients enrolled on the control arm.


Secondary Outcome Measures:
  • Toxicity, assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) [ Time Frame: 24 months post treatment ] [ Designated as safety issue: Yes ]
  • Time to biochemical recurrence [ Time Frame: 24 months post treatment ] [ Designated as safety issue: No ]
    Cox regression will be used with the log-rank test to compare time to biochemical recurrence in patients treated with axitinib to patients treated with surgery alone.

  • Time to metastatic recurrence [ Time Frame: 24 months post treatment ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: October 2011
Estimated Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: axitinib
Given PO
Other Name: AG-013736
Procedure: therapeutic conventional surgery
Undergo prostatectomy and pelvic lymph node dissection
Other: enzyme-linked immunosorbent assay
Correlative studies
Other Name: ELISA
Other: laboratory biomarker analysis
Correlative studies
Active Comparator: Arm II (surgery)
Patients undergo prostatectomy and pelvic lymph node dissection at 5-6 weeks after biopsy confirmation of prostate cancer.
Procedure: therapeutic conventional surgery
Undergo prostatectomy and pelvic lymph node dissection
Other: enzyme-linked immunosorbent assay
Correlative studies
Other Name: ELISA
Other: laboratory biomarker analysis
Correlative studies

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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
  • 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

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
    • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01385059

Locations
United States, California
City of Hope Medical Center
Duarte, California, United States, 91010
Sponsors and Collaborators
City of Hope Medical Center
Investigators
Principal Investigator: Sumanta Pal City of Hope Medical Center
  More Information

No publications provided

Responsible Party: City of Hope Medical Center
ClinicalTrials.gov Identifier: NCT01385059     History of Changes
Other Study ID Numbers: 10151, NCI-2011-01105
Study First Received: June 24, 2011
Last Updated: July 17, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Diseases, Male
Genital Neoplasms, Male
Neoplasms
Neoplasms by Site
Prostatic Diseases
Urogenital Neoplasms
Axitinib
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on October 20, 2014