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Saracatinib in Treating Patients With Prostate Cancer

A Randomized Discontinuation Phase 2 Study of AZD0530 as a Metastasis Inhibitor in Castrate Resistant Prostate Cancer

Status
Terminated
Phases
Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT01267266
Enrollment
31
Registered
2010-12-28
Start date
2010-12-31
Completion date
2013-11-30
Last updated
2015-04-01

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

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

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.

Interventions

DRUGsaracatinib

Given orally

Given orally

Sponsors

National Cancer Institute (NCI)
Lead SponsorNIH

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
MALE
Healthy volunteers
No

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

Design outcomes

Primary

MeasureTime frameDescription
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

MeasureTime frameDescription
Toxicity and Incidence of Adverse EventsUp to 6 months.Percentage of patients with grade 4 toxicity.
Toxicity and Incidence of Adverse Events.Up to 6 months.Percentage of patients who discontinued therapy due to toxicity.
Correlation of Molecular Profile With Clinical OutcomesUp to 2 yearsStudy terminated after randomization of only 8 subjects. Correlative data not analyzed.

Countries

United States

Participant flow

Participants by arm

ArmCount
Arm I (Saracatinib)
Patients receive 175 mg oral saracatinib once daily on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
31
Total31

Withdrawals & dropouts

PeriodReasonFG000FG001
Enrollment PhaseWithdrawal by Subject20
Lead-in PhaseAdverse Event20
Lead-in PhaseLack of Efficacy200
Lead-in PhaseWithdrawal by Subject10

Baseline characteristics

CharacteristicArm I (Saracatinib)
Age, Continuous71 years
Sex: Female, Male
Female
0 Participants
Sex: Female, Male
Male
31 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
deaths
Total, all-cause mortality
— / —— / —— / —
other
Total, other adverse events
29 / 313 / 33 / 5
serious
Total, serious adverse events
1 / 310 / 31 / 5

Outcome results

Primary

Duration of Stable Disease. (Time to Disease Progression by CT and/or Bone Scan or Clinical Progression.)

Time to progression will be assessed using the Kaplan-Meier method and compared between groups via Wilcoxon rank-sum test.

Time frame: Up to 6 months.

Population: Two patients in the placebo arm censored at 12 and 17 weeks, respectively.

ArmMeasureValue (MEDIAN)
Arm I (Saracatinib)Duration of Stable Disease. (Time to Disease Progression by CT and/or Bone Scan or Clinical Progression.)18 weeks
Arm II (Placebo)Duration of Stable Disease. (Time to Disease Progression by CT and/or Bone Scan or Clinical Progression.)12 weeks
p-value: 0.2Log Rank
Secondary

Correlation of Molecular Profile With Clinical Outcomes

Study terminated after randomization of only 8 subjects. Correlative data not analyzed.

Time frame: Up to 2 years

Secondary

Toxicity and Incidence of Adverse Events

Percentage of patients with grade 4 toxicity.

Time frame: Up to 6 months.

ArmMeasureValue (NUMBER)
Arm I (Saracatinib)Toxicity and Incidence of Adverse Events0.0 percentage of participants
Arm II (Placebo)Toxicity and Incidence of Adverse Events0.0 percentage of participants
Secondary

Toxicity and Incidence of Adverse Events.

Percentage of patients who discontinued therapy due to toxicity.

Time frame: Up to 6 months.

ArmMeasureValue (NUMBER)
Arm I (Saracatinib)Toxicity and Incidence of Adverse Events.0.0 percentage of participants
Arm II (Placebo)Toxicity and Incidence of Adverse Events.20.0 percentage of participants

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026