Prostate Cancer
Conditions
Brief summary
This trial will investigate the activity of dasatinib plus LHRH analogue therapy in high-risk localized prostate cancer.
Detailed description
OUTLINE: This is a multi-center study. * Dasatinib -100 mg administered once daily per oral route for 28 consecutive days. * Leuprolide acetate - 7.5 mg administered subcutaneously on day 1 every 28 days (+ 7 days). The 28 days of dasatinib and leuprolide injection (plus the time required to recover from toxicity if encountered) is defined as a cycle. Patients will be treated for up to a maximum of 3 cycles of dasatinib and leuprolide acetate. Radical Prostatectomy should be performed no sooner than 8 hours but preferably within 24 hours of the last administered dasatinib dose. All attempts should be made for the patient to have their surgery after 8 hours but within 24 hours of their last dose of dasatinib. If surgery delay is imperative, dasatinib therapy should continue until at least 24 hours before planned surgery. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 Hematopoietic: * Hemoglobin (Hgb) ≥ 8.0 g/dL * Platelets ≥ 100 K/mm3 * Absolute neutrophil count (ANC) ≥ 1.0 K/mm3 Hepatic: * Total bilirubin \< 2.0 X Upper Limit Normal (ULN) * Aspartate aminotransferase (AST) \< 2.5 X ULN * Alanine aminotransferase (ALT) \< 2.5 X ULN Renal: * Calculated creatinine clearance of ≥ 60 cc/min using the Cockcroft-Gault formula Cardiovascular: * No uncontrolled angina, congestive heart failure or myocardial infarction within 6 months prior to registration for protocol therapy.
Interventions
DRUGDasatinib
Dasatinib 100 mg administered once daily per oral route for 28 consecutive days
DRUGLeuprolide Acetate (LHRH Analogue)
Leuprolide acetate 7.5 mg administered subcutaneously on day 1 every 28 days (+ 7 days).
PROCEDURERadical Prostatectomy
Radical prostatectomy should be performed no sooner than 8 hours but preferably within 24 hours of the last administered dasatinib dose.
Sponsors
Bristol-Myers Squibb
Noah Hahn, M.D.
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 confirmed adenocarcinoma of the prostate. * Clinical stage T1-T3a disease. * Must be willing to have a tumor biopsy, if previous tumor tissue unavailable for tumor marker analysis. * Kattan pre-operative nomogram-predicted (based on stage, Prostate Specific Antigen (PSA) and Gleason score) 5-year risk of recurrence-free survival of 80% or less * Must be deemed eligible for radical prostatectomy. * Must be willing to use an effective method of contraception (hormonal or barrier method of birth control; abstinence) from the time consent is signed until 6 weeks after treatment discontinuation. * Written informed consent and HIPAA authorization for release of personal health information. * Age \> 18 years at the time of consent.
Exclusion criteria
* No evidence of regional, lymph node or distant metastasis on clinical or radiological assessments. All baseline radiology studies must be performed within 28 days prior to registration for protocol therapy. * No prior malignancy in the past 2 years except for basal cell and squamous cell carcinoma of the skin. Other cancers with low potential for metastasis, such as in situ cancers (e.g., Grade 1, TA TCC (low grade superficial bladder cancer), and colonic polyp with focus of adenocarcinoma) can be enrolled after approval from the Sponsor Investigator. * No prior hormonal therapy with the exception of oral 5-alpha-reductase inhibitors (finasteride, dutasteride, etc.). Patients who have received prior oral anti-androgen therapies (bicalutamide, flutamide, nilutamide, etc.), prior LHRH agonist therapy (leuprolide, goserelin acetate, etc.), or prior orchiectomy are ineligible. * No prior systemic chemotherapy or radiotherapy for prostate cancer is allowed. Transurethral resection of the prostate for benign prostatic hypertrophy (BPH) and oral alpha-blockers (terazosin, tamsulosin, doxazosin) are permitted. * No history of hemorrhage or thrombotic events (cerebrovascular accident, deep vein thrombosis, pulmonary embolism, etc.) within 6 months prior to registration for protocol therapy. * No history of diagnosed congenital bleeding disorders (e.g., von Willebrand's disease) * No history of diagnosed acquired bleeding disorder within one year (e.g., acquired anti-factor VIII antibodies) of registration on protocol therapy. * No history of ongoing or recent (≤ 3 months of registration on protocol therapy) significant gastrointestinal bleeding * No ongoing anti-coagulation and/or anti-platelet therapies allowed. * No unresolved pleural or pericardial effusion of any grade within 3 months of registration for protocol therapy. * No uncontrolled angina, congestive heart failure or MI within 6 months prior to registration for protocol therapy. * No diagnosed congenital long QT syndrome. * No history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de Pointes). * No prolonged QTc interval on pre-entry electrocardiogram (\> 450 msec) * Following medications must be discontinued at least 7 days prior to registration for protocol therapy and be withheld for the duration of dasatinib therapy: * Drugs that are generally accepted to have a risk of causing Torsades de Pointes * Patient must not be receiving any prohibited CYP3A4 inhibitors /inducers/ substrates * Anti-coagulation and/or anti-platelet therapies - to avoid potential bleeding risks. * No major surgical procedure, open biopsy, or significant trauma within 28 days prior to registration for protocol therapy. * Ability to comply with study and/or follow-up procedures and requirements. * No treatment with any investigational agent for any medical condition within 28 days prior to registration for protocol therapy. * No clinically significant infections or any other condition which, in the investigator's opinion, deems the patient an unsuitable candidate to receive the study drug. * Ability to take oral medication (dasatinib must be swallowed whole). * No known history of hypokalemia that cannot be corrected prior to registration on protocol therapy. * No known history of hypomagnesemia that cannot be corrected prior to registration on protocol therapy.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To Estimate the Pathologic Complete Response (pCR) Rate | 18 months |
Secondary
| Measure | Time frame |
|---|---|
| To Estimate Progression Free Survival | 18 months |
| To Estimate Partial Pathologic Responses (pPR) | 18 months |
| To Estimate PSA Response Rate | 18 months |
| To Evaluate the Impact of Dasatinib Plus LHRH on Expression of Selected Biomarkers | 18 months |
| To Estimate Safety and Tolerability of LHRH Plus Dasatinib | 18 months |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Experimental Arm Neoadjuvant dasatinib plus leuprolide acetate followed by radical prostatectomy
Dasatinib: Dasatinib 100 mg administered once daily per oral route for 28 consecutive days
Leuprolide Acetate (LHRH Analogue): Leuprolide acetate 7.5 mg administered subcutaneously on day 1 every 28 days (+ 7 days).
Radical Prostatectomy: Radical prostatectomy should be performed no sooner than 8 hours but preferably within 24 hours of the last administered dasatinib dose. | 1 |
| Total | 1 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Study Terminated | 1 |
Baseline characteristics
| Characteristic | Experimental Arm |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants |
| Region of Enrollment United States | 1 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 1 / 1 |
| serious Total, serious adverse events | 0 / 1 |
Outcome results
Primary
To Estimate the Pathologic Complete Response (pCR) Rate
Time frame: 18 months
Population: No participants were analyzed for pCR due to study termination
Secondary
To Estimate Partial Pathologic Responses (pPR)
Time frame: 18 months
Secondary
To Estimate Progression Free Survival
Time frame: 18 months
Secondary
To Estimate PSA Response Rate
Time frame: 18 months
Population: Data for this secondary objective was not collected or analyzed.
Secondary
To Estimate Safety and Tolerability of LHRH Plus Dasatinib
Time frame: 18 months
Secondary
To Evaluate the Impact of Dasatinib Plus LHRH on Expression of Selected Biomarkers
Time frame: 18 months