AZD0530 in Treating Patients With Prostate Cancer That Did Not Respond to Hormone Therapy

Phase 2

Completed

Conditions: Hormone-resistant Prostate Cancer
Recurrent Prostate Cancer

Interventions: Drug: saracatinib
Other: laboratory biomarker analysis

Registration Number: NCT00513071

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: This phase II trial is studying how well AZD0530 works in treating patients with prostate cancer that did not respond to hormone therapy. AZD0530 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth

Detailed Description: PRIMARY OBJECTIVES:

I. To test the hypothesis that AZD0530 will improve the prostate-specific antigen (PSA) response rate and progression-free survival (PFS) in comparison with historical controls for patients with hormone-refractory prostate cancer (HRPC).

II. Evaluate the time to treatment failure and overall survival of patients with HRPC treated with AZD0530.

III. Evaluate the toxicities and tolerance of AZD0530 therapy in the HRPC population.

OUTLINE: This is a multicenter study.

Patients receive oral AZD0530 once daily. Treatment repeats every 4 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 6 months for the first 2 years and then yearly thereafter.

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 28

Inclusion Criteria

Histologically or cytologically confirmed prostate cancer with a Gleason score available or interpretable and meeting 1 of the following criteria:
- No prior chemotherapy and relatively minimal cancer spread
- Only one prior taxane-based chemotherapy for aggressive and/or symptomatic disease
Must have prostate cancer considered to be hormone refractory or androgen independent by one or more of the following criteria (despite androgen deprivation and anti-androgen withdrawal when applicable):
- Progression of unidimensionally measurable disease assessed within 28 days prior to initial administration of drug
- Progression of evaluable but not measurable disease assessed within 28 days prior to initial administration of drug for PSA evaluation and within 42 days for imaging studies (e.g., bone scans)
Patients must have nonmeasurable disease (e.g., nuclear medicine bone scans) and non-target lesions (e.g., PSA level) assessed within 28 days prior to initial administration of drug
- Measurable disease is not required but is allowed
Must be surgically or medically castrated
- If the method of castration was luteinizing hormone-releasing hormone (LHRH) agonists (e.g., leuprolide or goserelin), then the patient must be willing to continue the use of LHRH agonists
- Serum testosterone must be at castrate levels (< 50 ng/dL) at least 3 months prior to registration
ECOG performance status 0-2
WBC >= 3,000/uL
Absolute neutrophil count >= 1,500/uL
Platelets >= 100,000/uL
Hemoglobin > 9 g/d
Total bilirubin within normal institutional limits
AST/ALT =< 2.5 x institutional upper limit of normal
Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min
Must agree to use adequate contraception prior to study entry and for the duration of study participation
At least 3 weeks since the completion of chemotherapy and radiotherapy and the patient must have recovered from the side effects of the therapy
At least 28 days since prior non-steroidal anti-androgens (e.g., flutamide) (42 days for bicalutamide or nilutamide) or hormonal treatment (e.g., ketoconazole) and demonstrated progression of disease since the agents were suspended
Concurrent bisphosphonate therapy is allowed

Exclusion Criteria

Known brain metastases
History of allergic reactions attributed to compounds of similar chemical or biological composition to AZD0530
Patients with any of the following conditions that impair the ability to swallow AZD0530 tablets
- Gastrointestinal tract disease resulting in an inability to take oral medication or requiring IV alimentation
- Prior surgical procedures affecting absorption
- Active peptic ulcer disease
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements
Patients who have not recovered from adverse events due to agents administered more than 4 weeks earlier
Use of specifically prohibited CYP3A4-active agents or substances
- 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
Patients receiving any other investigational agents
No investigational or commercial agents or therapies other than study drugs may be administered with the intent to treat the patient's malignancy
HIV-positive patients on combination antiretroviral therapy

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (saracatinib)	laboratory biomarker analysis	Patients receive oral AZD0530 once daily. Treatment repeats every 4 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity.
Treatment (saracatinib)	saracatinib	Patients receive oral AZD0530 once daily. Treatment repeats every 4 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
PSA Response Rate	PSA measured every 4 weeks	Complete Response (CR), disappearance of all measurable and non-measurable disease. No new lesions. PSA ≤ 0.2 ng/mL; Partial Response (PR), a decline in PSA by at least 30%, confirmed by a second PSA value four or more weeks later; Overall Response (OR) = CR + PR

Secondary Outcome Measures

Name	Time	Method
Toxicity Data	Up to 2 years	Toxicity assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. All grade 3 or worse toxicities (Possibly, Probably, or Definitely) attributed to AZD0530.
N-telopeptide and Deoxypyridinoline as Prognostic Bone Markers	At baseline, at 6 hours, at each course (day 1), and at 2 years
Time to Treatment Failure	From first day of treatment until discontinuation of treatment, up to 2 years	Defined as the time from start of treatment to the discontinuation of treatment for any reason, including disease progression, treatment toxicity, patient preference, or death Will be summarized using the Kaplan-Meier product-limit estimators. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Progression-free Survival (PFS)	From start of treatment until progression or death, up to 2 years	PFS defined as time between start of treatment and disease progression or death. Using the method of Kaplan-Meier. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Overall Survival	From start of treatment, up to 5 years	Estimated using the product-limit method of Kaplan and Meier.
Relationship Between Changes in Laboratory Correlates and Response and Survival	Up to 2 years