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A Randomized, Phase II Study Assessing Axitinib as Pre-Surgical Therapy in Patients With High Risk Prostate Cancer

Phase 2
18 Years
Open (Enrolling)
Stage III Prostate Cancer, Stage IV Prostate Cancer

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Trial Information

A Randomized, Phase II Study Assessing Axitinib as Pre-Surgical Therapy in Patients With High Risk Prostate Cancer


I. To determine if axitinib modulates pre-metastatic niche density in patients with
high-risk prostate cancer.


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.

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

- 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

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Pre-metastatic niche density

Outcome Description:

Defined by the average number of VEGFR1 clusters in 8 distinct 40X microscopic fields.

Outcome Time Frame:

Week 9 post treatment

Safety Issue:


Principal Investigator

Sumanta Pal

Investigator Role:

Principal Investigator

Investigator Affiliation:

City of Hope Medical Center


United States: Food and Drug Administration

Study ID:




Start Date:

October 2011

Completion Date:

Related Keywords:

  • Stage III Prostate Cancer
  • Stage IV Prostate Cancer
  • Prostatic Neoplasms



City of Hope Medical Center Duarte, California  91010