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

A Phase II Trial of AZD0530 in Hormone Refractory Prostate Cancer (HRPC)

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

Study Overview

• Status: Completed
• Conditions: Recurrent Prostate Cancer; Hormone-resistant Prostate Cancer
• Intervention / Treatment: Other: laboratory biomarker analysis; Drug: saracatinib

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.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • City Of Hope

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (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.	Other: laboratory biomarker analysis; Correlative studies; Drug: saracatinib; Given orally; Other Names: AZD0530

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PSA Response Rate	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	PSA measured every 4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS)	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.	From start of treatment until progression or death, up to 2 years
Time to Treatment Failure	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	From first day of treatment until discontinuation of treatment, up to 2 years
Overall Survival	Estimated using the product-limit method of Kaplan and Meier.	From start of treatment, up to 5 years
Toxicity Data	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.	Up to 2 years
Relationship Between Changes in Laboratory Correlates and Response and Survival		Up to 2 years
N-telopeptide and Deoxypyridinoline as Prognostic Bone Markers		At baseline, at 6 hours, at each course (day 1), and at 2 years

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Primo Lara, City of Hope Medical Center

Study record dates

Study Major Dates

• Study Start: August 1, 2007
• Primary Completion (Actual): October 1, 2008
• Study Completion (Actual): October 1, 2008

Study Registration Dates

• First Submitted: August 6, 2007
• First Submitted That Met QC Criteria: August 6, 2007
• First Posted (Estimate): August 8, 2007

Study Record Updates

• Last Update Posted (Actual): April 19, 2018
• Last Update Submitted That Met QC Criteria: March 21, 2018
• Last Verified: March 1, 2018

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; Antineoplastic Agents; Saracatinib
• Other Study ID Numbers: NCI-2012-02842; N01CM62201 (U.S. NIH Grant/Contract); PHII-79; N01CM62209 (U.S. NIH Grant/Contract); CDR0000559142 (Registry Identifier: PDQ (Physician Data Query))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No