Saracatinib in Treating Patients With Prostate Cancer

NCT ID: NCT01267266

Last Updated: 2015-04-01

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 31 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-12-31
• Study Completion Date: 2013-11-30

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.

Conditions

Hormone-resistant Prostate Cancer; Recurrent Prostate Cancer; Stage IV Prostate Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

saracatinib

Intervention Type: DRUG

Given orally

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.

Group Type: PLACEBO_COMPARATOR

hydrocortisone/placebo

Intervention Type: OTHER

Given orally

Interventions

saracatinib

Given orally

Intervention Type: DRUG

hydrocortisone/placebo

Given orally

Intervention Type: OTHER

Other Intervention Names

AZD0530

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

• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Walter Stadler

Role: PRINCIPAL_INVESTIGATOR

University of Chicago

Locations

University of Chicago

Chicago, Illinois, United States

Decatur Memorial Hospital

Decatur, Illinois, United States

NorthShore University HealthSystem-Evanston Hospital

Evanston, Illinois, United States

Ingalls Memorial Hospital

Harvey, Illinois, United States

Loyola University Medical Center

Maywood, Illinois, United States

Illinois CancerCare-Peoria

Peoria, Illinois, United States

Central Illinois Hematology Oncology Center

Springfield, Illinois, United States

Southern Illinois University

Springfield, Illinois, United States

Fort Wayne Medical Oncology and Hematology Inc-Parkview

Fort Wayne, Indiana, United States

University of Maryland Greenebaum Cancer Center

Baltimore, Maryland, United States

University of Michigan

Ann Arbor, Michigan, United States

Saint John's Mercy Medical Center

St Louis, Missouri, United States

M D Anderson Cancer Center

Houston, Texas, United States

University of Wisconsin Women's Health Center

Madison, Wisconsin, United States

Froedtert and the Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Countries

United States

Other Identifiers

NCI-2011-02563

Identifier Type: REGISTRY

Identifier Source: secondary_id

CDR0000691725

Identifier Type: -

Identifier Source: secondary_id

10-436-B

Identifier Type: OTHER

Identifier Source: secondary_id

8446

Identifier Type: OTHER

Identifier Source: secondary_id

N01CM00099

Identifier Type: NIH

Identifier Source: secondary_id

View Link

N01CM00071

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U01CA062491

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P30CA014599

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2011-02563

Identifier Type: -

Identifier Source: org_study_id