Saracatinib in Treating Patients With Prostate Cancer

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01267266
First received: December 24, 2010
Last updated: April 1, 2014
Last verified: January 2013
  Purpose

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.


Condition Intervention Phase
Hormone-resistant Prostate Cancer
Recurrent Prostate Cancer
Stage IV Prostate Cancer
Drug: saracatinib
Other: hydrocortisone/placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Discontinuation Phase 2 Study of AZD0530 as a Metastasis Inhibitor in Castrate Resistant Prostate Cancer

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Time to disease progression by CT and/or bone scan [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Time to progression will be assessed using the Kaplan-Meier method and compared between groups via the logrank test.

  • PFS [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Will be assessed using the Kaplan-Meier method and compared between groups via the logrank test.


Secondary Outcome Measures:
  • Toxicity and incidence of adverse events [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]
    Toxicities will be summarized by type and grade.

  • PSA response [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    PSA levels post-randomization will be analyzed using mixed models for longitudinal data.

  • Correlation of molecular profile with clinical outcomes [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]

Enrollment: 32
Study Start Date: December 2010
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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

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

Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01267266

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

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01267266     History of Changes
Other Study ID Numbers: NCI-2011-02563, NCI-2011-02563, CDR0000691725, 10-436-B, 8446, N01CM00099, N01CM00071, U01CA062491, P30CA014599
Study First Received: December 24, 2010
Last Updated: April 1, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Hydrocortisone acetate
Hydrocortisone 17-butyrate 21-propionate
Cortisol succinate
Hydrocortisone
Hydrocortisone-17-butyrate
Saracatinib
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Dermatologic Agents
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 28, 2014