Hormone-resistant Prostate Cancer, Recurrent Prostate Cancer
Conditions
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.
Interventions
DRUGsaracatinib
Given orally
OTHERlaboratory biomarker analysis
Correlative studies
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Overall Survival | From start of treatment, up to 5 years | Estimated using the product-limit method of Kaplan and Meier. |
| 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. |
| 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 | — |
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Saracatinib) Patients receive oral AZD0530 at 175 mg once daily. Treatment repeats every 4 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity.
saracatinib: Given orally
laboratory biomarker analysis: Correlative studies | 28 |
| Total | 28 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Physician Decision | 3 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Treatment (Saracatinib) |
|---|---|
| Age, Continuous | 67 years |
| Region of Enrollment United States | 28 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 28 |
| other Total, other adverse events | 26 / 28 |
| serious Total, serious adverse events | 5 / 28 |
Outcome results
Primary
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
Time frame: PSA measured every 4 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Saracatinib) | PSA Response Rate | 0 percentage of participants |
Secondary
N-telopeptide and Deoxypyridinoline as Prognostic Bone Markers
Time frame: At baseline, at 6 hours, at each course (day 1), and at 2 years
Population: Bone marker data was not collected.
Secondary
Overall Survival
Estimated using the product-limit method of Kaplan and Meier.
Time frame: From start of treatment, up to 5 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Saracatinib) | Overall Survival | 26.0 Months |
Secondary
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.
Time frame: From start of treatment until progression or death, up to 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Saracatinib) | Progression-free Survival (PFS) | 1.9 Months |
Secondary
Relationship Between Changes in Laboratory Correlates and Response and Survival
Time frame: Up to 2 years
Population: Laboratory correlates were not collected.
Secondary
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
Time frame: From first day of treatment until discontinuation of treatment, up to 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Saracatinib) | Time to Treatment Failure | 1.9 Months |
Secondary
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.
Time frame: Up to 2 years
Population: One patient died unexpectedly at home. No autopsy was performed. Treatment was listed as possible cause along with diabetes mellitus, morbid obesity, hypertension, hypercholesterolemia, and renal failure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment (Saracatinib) | Toxicity Data | Grade 3 : Alanine aminotransferase (ALT) | 1 participants |
| Treatment (Saracatinib) | Toxicity Data | Grade 3 : Asparate aminotransferase (AST) | 1 participants |
| Treatment (Saracatinib) | Toxicity Data | Grade 3 : Nausea | 1 participants |
| Treatment (Saracatinib) | Toxicity Data | Grade 3 : Vomiting | 1 participants |
| Treatment (Saracatinib) | Toxicity Data | Grade 3 : Lymphopenia | 1 participants |
| Treatment (Saracatinib) | Toxicity Data | Grade 3 : Death, not associated with CTC term | 0 participants |
| Treatment (Saracatinib) | Toxicity Data | Grade 5 : Alanine aminotransferase (ALT) | 0 participants |
| Treatment (Saracatinib) | Toxicity Data | Grade 5 : Asparate aminotransferase (AST) | 0 participants |
| Treatment (Saracatinib) | Toxicity Data | Grade 5 : Nausea | 0 participants |
| Treatment (Saracatinib) | Toxicity Data | Grade 5 : Vomiting | 0 participants |
| Treatment (Saracatinib) | Toxicity Data | Grade 5 : Lymphopenia | 0 participants |
| Treatment (Saracatinib) | Toxicity Data | Grade 5 : Death, not associated with CTC term | 1 participants |