Saracatinib in Treating Patients With Prostate Cancer

Phase 2

Terminated

Conditions: Hormone-resistant Prostate Cancer
Recurrent Prostate Cancer
Stage IV Prostate Cancer

Interventions: Other: hydrocortisone/placebo
Drug: saracatinib

Registration Number: NCT01267266

Lead Sponsor: National Cancer Institute (NCI)

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.

Recruitment & Eligibility

Status: TERMINATED

Sex: Male

Target Recruitment: 31

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

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm II (placebo)	hydrocortisone/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.
Arm I (saracatinib)	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.

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (15): University of Chicago
🇺🇸
Chicago, Illinois, United States
University of Maryland Greenebaum Cancer Center
🇺🇸
Baltimore, Maryland, United States
Decatur Memorial Hospital
🇺🇸
Decatur, Illinois, United States
M D Anderson Cancer Center
🇺🇸
Houston, Texas, United States
Loyola University Medical Center
🇺🇸
Maywood, Illinois, United States
NorthShore University HealthSystem-Evanston Hospital
🇺🇸
Evanston, Illinois, United States
Ingalls Memorial Hospital
🇺🇸
Harvey, 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
Saint John's Mercy Medical Center
🇺🇸
Saint Louis, Missouri, United States
University of Wisconsin Women's Health Center
🇺🇸
Madison, Wisconsin, United States
University of Michigan
🇺🇸
Ann Arbor, Michigan, United States
Froedtert and the Medical College of Wisconsin
🇺🇸
Milwaukee, Wisconsin, United States