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A Phase II Study of SU011248 in Men With Advanced Prostate Cancer

Phase 2
18 Years
Not Enrolling
Prostate Cancer

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Trial Information

A Phase II Study of SU011248 in Men With Advanced Prostate Cancer

Background: There are nearly 30,000 deaths per year in the United States from prostate
cancer, making this a large and important target patient population for new therapeutics.
The mainstay of therapy for advanced prostate cancer is androgen deprivation therapy (ADT).
Although ADT is effective in the large majority of men with advanced prostate cancer, the
favorable response to ADT is only transient. In hormone-refractory, metastatic prostate
cancer the only effective systemic treatment is cytotoxic chemotherapy. The median duration
of response to standard, taxane-based chemotherapy is approximately six months, and median
survival in contemporary studies is only 16-18 months. Thus, there is an urgent need for
new therapeutic agents to treat advanced prostate cancer.

SU011248 is an orally administered inhibitor of the vascular endothelial growth factor
(VEGF) receptors, platelet-derived growth factor (PDGF) receptor, FLT-3 and c-KIT. SU011248
has demonstrated significant clinical activity in other malignancies, but its activity in
prostate cancer has not been studied to date. Clinical trials have demonstrated that
SU011248 is generally well tolerated, with mild fatigue and diarrhea the most common adverse
effects. Preclinical studies have demonstrated that levels of VEGF and PDGF are elevated in
prostate cancer and may correlate with worse outcome. The inhibition of several pathways
implicated in prostate cancer progression by SU011248 suggests that it might have
significant anti-tumor activity in men with AIPC.

Many of the new, targeted agents are efficacious in only a subset of patients with a
particular malignancy, and these subsets may be definable on the basis of specific tumor
mutations or patterns of gene expression. Identification of reliable predictive methods is
crucial in moving forward with targeted therapies, and we believe that exploratory clinical
trials such as this one should incorporate assays designed to address this issue.

Objective/Hypothesis: The objective of this proposal is to determine whether SU011248 is an
effective treatment in two cohorts of men with advanced prostate cancer: men with
androgen-independent prostate cancer (AIPC) who have not been treated with chemotherapy
(Group A), and men with taxane-refractory, metastatic disease (Group B). We hypothesize
that specific serum biomarkers and tumor mutations may predict response and may allow
optimal subject selection in the future.

Specific Aims: (1) To evaluate the efficacy and safety of SU011248 in men with chemo-naïve
AIPC, (2) to evaluate the efficacy and safety of SU011248 in men with metastatic,
taxane-resistant AIPC, (3) to measure serum biomarkers in men with AIPC prior to and
following treatment with SU011248 and correlate these markers with clinical response, and
(4) to mutational analysis from tumor specimens of men with metastatic prostate cancer
treated with SU011248 and correlate with clinical response.

Study Design: We will conduct a phase II clinical trial in two groups of subjects: men with
AIPC who have not yet developed overt metastases (Group A), and men with taxane-refractory,
metastatic disease (Group B). Men in both groups will receive single-agent SU011248 on a
six-week repeating schedule, with four weeks of daily treatment followed by a two-week rest.
The primary endpoint will be PSA response rate. Secondary endpoints will include time to
disease progression, objective response rate, and safety parameters. Eligibility for this
study will require signed informed consent, adenocarcinoma of the prostate, documented PSA
progression despite ADT, reasonable functional status, resolution of toxic effects from
prior treatments, and acceptable bone marrow, hepatic, renal and cardiac function. A
Simon's two-stage design will be employed to allow early termination for lack of efficacy.
Ultimately, 30 patients will be enrolled in each group, for a total of 60 patients. A
defined program of history and physical examinations, radiographic studies, and laboratory
tests including PSA will be carried out to determine the efficacy and safety of SU011248 in
this patient population.

All subjects will have blood and urine collected for research purposes, and men in Group B
will have tumor biopsy prior to enrollment. Translational studies aimed at identifying
specific biomarkers in the blood will include analysis of serum cytokine levels including
VEGF and others, circulating endothelial cells and endothelial precursors, white blood cell
differential, and bone turnover markers. Tumor samples will be analyzed for the presence of
predictive tumor mutations.

Relevance: Our ultimate goals are to determine whether SU011248 is an important therapeutic
agent in men with advanced prostate cancer, and to identify predictive markers of
anti-cancer activity within individual subjects that would allow selective treatment of
appropriate subjects in the future. The data obtained should also contribute to our general
understanding of serum biomarkers and genetic changes in advanced prostate cancer. Positive
results of our trial would lead to expanded, multi-center trials of SU011248 in men with
advanced prostate cancer.

Inclusion Criteria:

- Signed informed consent indicating that the subject has been informed of all
pertinent aspects of the trial.

- Adenocarcinoma of the prostate

- Male subjects, 18 years of age or older

- Life expectancy of > 12 weeks

- Resolution of all acute toxic effects of prior chemotherapy, radiotherapy or surgical
procedure to National Cancer Institute Common Toxicity Criteria Adverse Event (NCI
CTCAE) grade <1

- Surgical or ongoing chemical castration

- Androgen-independent disease, defined as progressive disease despite surgical or
ongoing chemical castration. See section 8.2.3 for definition of progressive

- Eastern Cooperative Oncology Group performance status of 0, 1 or 2

- Adequate bone marrow reserve:

- Neutrophil count > 1,500/ul

- Platelet count > 75,000/ul

- Adequate hepatic function:

- Serum bilirubin < 1.5 x upper limit of normal

- Asparate aminotransferase and alanine aminotransferase < 2.5 x upper limit of

- Adequate renal function, with serum creatinine < 2 x upper limit of normal

- Prostate Specific Antigen (PSA) > 5.0 ng/mL, based on PSA Working Group Criteria

- Willingness and ability to comply with scheduled visits, treatment plans, laboratory
tests and other study procedures

For Group A only:

· No prior treatment for prostate cancer with cytotoxic chemotherapy

For Group B only:

- Radiographic evidence of metastatic prostate cancer

- One prior docetaxel-based chemotherapy regimen, minimum of two cycles

- Disease progression during treatment with docetaxel, or within 60 days of receiving

Exclusion Criteria:

- Small cell carcinoma of the prostate

- Treatment with extensive external beam radiation therapy or radionuclide therapy
within six weeks of study entry. Palliative radiation involving less than 20% of
bone marrow reserves must have been completed within four weeks of entry.

- Any of the following within the prior 6 months: unstable angina, myocardial
infarction, symptomatic congestive heart failure or cerebrovascular accident

- Receipt of any investigational anti-cancer agent within 4 weeks of the study

- NCI CTCAE grade 3 hemorrhage < 4 weeks of starting study treatment

- Uncontrolled hypertension

- Prolongation of the QTc interval to > 450 msec

- Other serious acute or chronic medical or psychiatric condition that may increase the
risk associated with study participation, and in the judgment of the investigator
would make the subject inappropriate for entry into this study.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

The Number of Men With Advanced Prostate Cancer Treated With Sunitinib Who Have a Prostate Specific Antigen (PSA) Response

Outcome Description:

Prostate specific antigen (PSA) responses, defined as the number of men who exhibit PSA decline of at least 50% that is confirmed by a second PSA value 4 or more weeks later (PSA Working Group I Criteria)

Outcome Time Frame:

were followed until disease progression, an average of 12 weeks

Safety Issue:


Principal Investigator

Dror Michaelson, MD PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Massachusetts General Hospital


United States: Food and Drug Administration

Study ID:




Start Date:

March 2006

Completion Date:

June 2008

Related Keywords:

  • Prostate Cancer
  • Sutent
  • Sunitinib
  • Bone
  • Metastatic
  • Hormone-refractory
  • Biomarkers
  • Prostatic Neoplasms



Massachusetts General Hospital Boston, Massachusetts  02114-2617
Dana Farber Cancer Institute Boston, Massachusetts  02115
Beth Israel-Deaconess Medical Center Boston, Massachusetts  02215