Clinical trial NCT01267266: Saracatinib in Treating Patients With Prostate Cancer
Official title: A Randomized Discontinuation Phase 2 Study of AZD0530 as a Metastasis Inhibitor in Castrate Resistant Prostate Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Hormone-resistant Prostate Cancer
Recurrent Prostate Cancer
Stage IV Prostate Cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2010-12-28
Enrollment: 31
Sex: MALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This randomized phase II clinical trial is studying how well saracatinib works in treating patients with prostate cancer. Saracatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed description: PRIMARY OBJECTIVES:

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

SECONDARY OBJECTIVES:

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.

Eligibility criteria: 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 CRPC
* 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 orchiectomy
* 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 disease)

  * 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 radiotherapy
* 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

Primary outcomes:
measure: Duration of Stable Disease. (Time to Disease Progression by CT and/or Bone Scan or Clinical Progression.)
timeFrame: Up to 6 months.
Secondary outcomes:
measure: Toxicity and Incidence of Adverse Events
timeFrame: Up to 6 months.
measure: Toxicity and Incidence of Adverse Events.
timeFrame: Up to 6 months.
measure: Correlation of Molecular Profile With Clinical Outcomes
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Decatur
country: United States
facility: Decatur Memorial Hospital
state: Illinois
city: Evanston
country: United States
facility: NorthShore University HealthSystem-Evanston Hospital
state: Illinois
city: Harvey
country: United States
facility: Ingalls Memorial Hospital
state: Illinois
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Peoria
country: United States
facility: Illinois CancerCare-Peoria
state: Illinois
city: Springfield
country: United States
facility: Central Illinois Hematology Oncology Center
state: Illinois
city: Springfield
country: United States
facility: Southern Illinois University
state: Illinois
city: Fort Wayne
country: United States
facility: Fort Wayne Medical Oncology and Hematology Inc-Parkview
state: Indiana
city: Baltimore
country: United States
facility: University of Maryland Greenebaum Cancer Center
state: Maryland
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Saint Louis
country: United States
facility: Saint John's Mercy Medical Center
state: Missouri
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
city: Madison
country: United States
facility: University of Wisconsin Women's Health Center
state: Wisconsin
city: Milwaukee
country: United States
facility: Froedtert and the Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: University of Chicago
name: Walter Stadler
role: PRINCIPAL_INVESTIGATOR
References: