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A Randomized Discontinuation Phase 2 Study of AZD0530 as a Metastasis Inhibitor in Castrate Resistant Prostate Cancer

Phase 2
Open (Enrolling)
Hormone-resistant Prostate Cancer, Recurrent Prostate Cancer, Stage IV Prostate Cancer

Thank you

Trial Information

A Randomized Discontinuation Phase 2 Study of AZD0530 as a Metastasis Inhibitor in Castrate Resistant Prostate Cancer


I. Determine if AZD0530 (saracatinib) increases time to radiographic progression in men with
CRPC compared to placebo.


I. Describe the adverse events related to AZD0530 in this population. II. Explore the role
of FYN and other SRC kinase expression as a predictor of response to AZD0530.

OUTLINE: This is a multicenter study.

LEAD-IN PHASE: Patients receive oral saracatinib once daily during for 8 weeks. Patients who
achieve disease regression or a PSA decrease of > 50% continue to receive open-label
saracatinib. Patients who do not show radiographic evidence of new metastases on bone scan
and CT, disease regression, or a > 50% decrease in PSA continue on to the randomized phase.

RANDOMIZED PHASE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive oral saracatinib once daily on days 1-28. Courses repeat every 4
weeks in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive oral placebo once daily on days 1-28. Courses repeat every 4 weeks
in the absence of disease progression or unacceptable toxicity. Upon progression, patients
may crossover to arm I.

Tissue samples may be collected for correlative studies. After completion of study
treatment, patients are followed up for 12 months.

Inclusion Criteria:

- Histologically or cytologically confirmed prostate cancer with progressive disease;
progressive disease may be defined as either

- New clinical or radiographic metastases

- Rising PSA: PSA must be greater than 1.0 ng/mL with at least 2 consecutive rises
after completion of prior therapy; the PSA values documenting these rises should
be separated by no less than 10 days; the baseline PSA value may be taken from
the end of prior therapy

- Previous treatment with docetaxel for disease progression following hormonal therapy
(i.e., castrate-resistant disease) required

- Treatment in the adjuvant or neoadjuvant setting will NOT be grounds for
inclusion unless docetaxel has been used again in the setting of progressive

- ECOG performance status 0-1

- ANC ≥ 1,500/mm³

- Hemoglobin > 9.0 g/dL

- Platelet count > 100,000/mm³

- Total bilirubin < 2.0 x institutional ULN

- AST/ALT < 5 x institutional ULN in the presence of bone/liver metastases

- Serum creatinine (Cr) within ULN

- Patients with Cr > ULN must have a Cr clearance of > 60 mL/min

- Testosterone 50 ng/mL or lower if a patient is receiving an LHRH agonist

- No testosterone testing is required for men who have undergone surgical

- Fertile patients must agree to abstinence or some adequate form of contraception

- No patients with any condition (e.g., gastrointestinal tract disease resulting in an
inability to take oral medication or a requirement for IV alimentation, prior
surgical procedures affecting absorption, or active peptic ulcer disease) that
impairs the ability to swallow AZD0530 tablets

- No history of uncontrolled or unstable cardiac dysrhythmia

- No resting ECG with measurable QTc interval of > 480 msec at 2 or more time points
within a 24-hour period

- No evidence of interstitial lung disease (bilateral, diffuse, parenchymal lung

- A high-resolution CT of the chest will be required during screening

- No evidence of severe or uncontrolled systemic conditions (e.g., severe hepatic
impairment) or current unstable or uncompensated respiratory or cardiac conditions
which makes it undesirable for the patient to participate in the study or which could
jeopardize compliance with the protocol

- No patients with a known immunodeficiency syndrome

- No patients with a history of allergic reactions attributed to compounds of similar
chemical or biologic composition to AZD0530

- No patients receiving any other investigational agents

- Previous AZD0530 exposure is allowed provided that the patient did not show
radiographic progression during treatment

- Patients receiving non-steroidal anti-androgens (e.g., flutamide) or other hormonal
treatment (such as ketoconazole, abiraterone, or TAK-700) must have stopped these
drugs at least 28 days prior to enrollment for flutamide or ketoconazole, or at least
42 days prior to enrollment for bicalutamide or nilutamide, and the patients must
have demonstrated progression of disease since the agents were suspended

- Patients should be at least 2 weeks away from previous chemotherapy, surgery, or

- No unresolved toxicity from previous treatments that are CTCAE grade 2 from previous
anti-cancer therapy (except alopecia)

- Patients who are currently on zoledronic acid (Zometa) or other bisphosphonate
therapy are eligible provided that they have been on therapy at least 6 weeks prior
to participation

- Increases in bisphosphonate dosing will not be allowed (i.e., starting within 6
weeks or changing from every 3-month to every 1-month dosing)

- Use of specifically prohibited CYP3A4-active agents or substances are not permitted
during protocol treatment, and patients who must continue treatment with these agents
are not eligible

- Prohibited drugs should be discontinued 7 days prior to the administration of
the first dose of AZD0530 and for 7 days following discontinuation of AZD0530
(unless otherwise specified)

- No concurrent use of non-FDA approved medications

Type of Study:


Study Design:

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

Outcome Measure:

Time to disease progression by CT and/or bone scan

Outcome Description:

Time to progression will be assessed using the Kaplan-Meier method and compared between groups via the logrank test.

Outcome Time Frame:

Up to 2 years

Safety Issue:


Principal Investigator

Walter Stadler

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Chicago Comprehensive Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

December 2010

Completion Date:

Related Keywords:

  • Hormone-resistant Prostate Cancer
  • Recurrent Prostate Cancer
  • Stage IV Prostate Cancer
  • Prostatic Neoplasms



Loyola University Medical Center Maywood, Illinois  60153
Ingalls Memorial Hospital Harvey, Illinois  60426
Central Illinois Hematology Oncology Center Springfield, Illinois  62701
Decatur Memorial Hospital Decatur, Illinois  62526
University of Chicago Comprehensive Cancer Center Chicago, Illinois  60637-1470
M D Anderson Cancer Center Houston, Texas  77030
Froedtert and the Medical College of Wisconsin Milwaukee, Wisconsin  53226
Evanston CCOP-NorthShore University HealthSystem Evanston, Illinois  60201
Illinois CancerCare-Peoria Peoria, Illinois  61615
Fort Wayne Medical Oncology and Hematology Inc - State Boulevard Fort Wayne, Indiana  46845
Saint John's Mercy Medical Center Saint Louis, Missouri  63141
University of Maryland Greenebaum Cancer Center Baltimore, Maryland  21201
University of Michigan University Hospital Ann Arbor, Michigan  48109
Southern Illinois University Springfield, Illinois  62702