Saracatinib in Treating Patients With Prostate Cancer

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

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.

Study Overview

• Status: Terminated
• Conditions: Recurrent Prostate Cancer; Hormone-resistant Prostate Cancer; Stage IV Prostate Cancer
• Intervention / Treatment: Drug: saracatinib; Other: hydrocortisone/placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
    • Decatur, Illinois, United States, 62526
      • Decatur Memorial Hospital
    • Evanston, Illinois, United States, 60201
      • NorthShore University HealthSystem-Evanston Hospital
    • Harvey, Illinois, United States, 60426
      • Ingalls Memorial Hospital
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
    • Peoria, Illinois, United States, 61615
      • Illinois CancerCare-Peoria
    • Springfield, Illinois, United States, 62702
      • Southern Illinois University
    • Springfield, Illinois, United States, 60702
      • Central Illinois Hematology Oncology Center
  • Indiana
    • Fort Wayne, Indiana, United States, 46845
      • Fort Wayne Medical Oncology and Hematology Inc-Parkview
  • Maryland
    • Baltimore, Maryland, United States, 21201-1595
      • University of Maryland Greenebaum Cancer Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • Saint John's Mercy Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • M D Anderson Cancer Center
  • Wisconsin
    • Madison, Wisconsin, United States, 53715
      • University of Wisconsin Women's Health Center
    • Milwaukee, Wisconsin, United States, 53226
      • Froedtert and the Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Arm I (saracatinib); Patients receive oral saracatinib once daily on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.	Drug: saracatinib; Given orally; Other Names: AZD0530
PLACEBO_COMPARATOR: Arm II (placebo); 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.	Other: hydrocortisone/placebo; Given orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Stable Disease. (Time to Disease Progression by CT and/or Bone Scan or Clinical Progression.)	Time to progression will be assessed using the Kaplan-Meier method and compared between groups via Wilcoxon rank-sum test.	Up to 6 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Toxicity and Incidence of Adverse Events	Percentage of patients with grade 4 toxicity.	Up to 6 months.
Toxicity and Incidence of Adverse Events.	Percentage of patients who discontinued therapy due to toxicity.	Up to 6 months.
Correlation of Molecular Profile With Clinical Outcomes	Study terminated after randomization of only 8 subjects. Correlative data not analyzed.	Up to 2 years

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: December 1, 2010
• Primary Completion (ACTUAL): September 1, 2012
• Study Completion (ACTUAL): November 1, 2013

Study Registration Dates

• First Submitted: December 24, 2010
• First Submitted That Met QC Criteria: December 24, 2010
• First Posted (ESTIMATE): December 28, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): April 1, 2015
• Last Update Submitted That Met QC Criteria: March 18, 2015
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Hydrocortisone; Saracatinib
• Other Study ID Numbers: NCI-2011-02563 (REGISTRY: CTRP (Clinical Trial Reporting Program)); P30CA014599 (U.S. NIH Grant/Contract); U01CA062491 (U.S. NIH Grant/Contract); N01CM00071 (U.S. NIH Grant/Contract); N01CM00099 (U.S. NIH Grant/Contract); CDR0000691725; 10-436-B (OTHER: University of Chicago); 8446 (OTHER: CTEP)