Prostate Cancer
Conditions
Keywords
AIPC
Brief summary
The primary objective of this study is to evaluate the safety of combining Sorafenib and chemotherapy (mitoxantrone or docetaxel) in patients with AIPC.
Detailed description
Patients who have AIPC and are progressing despite systemic chemotherapy will be offered participation in this study. Patients who relapse or progress shortly (within 12 weeks) after discontinuation of chemotherapy with either docetaxel/prednisone or mitoxantrone/prednisone will also be offered participation in this trial. Enrolled patients will receive sorafenib as per protocol define dose. Sorafenib will be administered in combination with the last chemotherapy utilized. If there is no disease progression after 6 cycles, chemotherapy will be stopped and Sorafenib may continue until disease progression.
Interventions
DRUGSorafenib
400mg twice daily
Sponsors
Oncology Specialists, S.C.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* Age \> 18 years old * Eastern Cooperative Oncology Group (ECOG) Performance Status 0, 1, or 2. * Patients with a known diagnosis of prostate cancer regardless of their Gleason grade. * Patients have AIPC. * Adequate bone marrow, liver and renal function as assessed by: * Hemoglobin \> 9.0 g/dl * absolute neutrophil count (ANC) \> 1,000/mm3 * Platelet count \> 75,000/mm3 * Total bilirubin \< 1.5 x upper limit of normal (ULN) * Alanine transaminase (ALT) and aspartate aminotransferase (AST) \< 2.5 x the ULN (\< 5 x ULN for patients with liver involvement). international normalized ratio (INR) \< 1.5 or a Prothrombin time (PT)/partial thromboplastin time (PTT) within normal limits. Patients receiving anti-coagulation treatment with an agent such as warfarin or heparin may be allowed to participate. * Creatinine \< 1.5 x ULN * Transfusions and the use of growth factors (for red and white cells) are allowed * Patients must have received either docetaxel or mitoxantrone as the chemotherapy regimen * Ability to understand and willingness to sign a written informed consent. A signed informed consent must be obtained prior to any study specific procedures. * Patients must have progressed while receiving systemic chemotherapy for AIPC. Patients could have progressed within 12 weeks of their last systemic chemotherapy administration. The definition of progression is defined as follows: * 1-For patients who are receiving systemic chemotherapy (one criteria is sufficient): * Increase in prostate-specific antigen (PSA) by 25% or more than the previous value. This should be repeated within 3 weeks (while patient is off chemotherapy) to confirm that the PSA did not decrease. * For patients with visceral disease, radiographic evidence of progression by standard Response Evaluation Criteria in Solid Tumors (RECIST) criteria (regardless of the PSA value). * For patients with bone only disease, progression on a whole body bone scan (2 or more new lesions) is sufficient to fulfill the definition of progressive disease, regardless of PSA value or the visceral disease status. * 2-For patients who have received chemotherapy previously (Both criteria are needed): * Not more than 12 weeks have elapsed since last chemotherapy administration * Either biochemical progression (25% increase in PSA that is confirmed with a repeat analysis within 3 weeks), OR radiographic progression (RECIST criteria for visceral disease patients OR 2 or more lesions on a whole body bone scan)
Exclusion criteria
* Cardiac disease: Congestive heart failure \> class II New York Heart Association 9NYHA). Patients must not have unstable angina or new onset angina or myocardial infarction within the past 6 months. * Known brain metastasis. Patients with neurological symptoms must undergo a CT scan or MRI of brain to exclude brain metastasis. * Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy. Patients with history of chronic and well controlled atrial fibrillation are allowed. Beta-blockers, calcium channel blockers, or digoxin are not considered anti-arrhythmics. * Uncontrolled hypertension defined as systolic blood pressure \> 150 mmHg or diastolic pressure \> 90 mmHg, despite optimal medical management. * Sorafenib is contraindicated in patients with known severe hypersensitivity to sorafenib or any of the excipients. * Known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C. * Active clinically serious infection \> Common Toxicity Criteria for Adverse Effects (CTCAE) Grade 2. * Thrombolic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months. * Pulmonary hemorrhage/bleeding event \> CTCAE Grade 2 within 4 weeks of first dose of study drug. * Any other hemorrhage/bleeding event \> CTCAE Grade 3 within 4 weeks of first dose of study drug. * Serious non-healing wound, ulcer, or bone fracture. * Evidence or history of bleeding diathesis or uncontrolled coagulopathy. * Major surgery, open biopsy or significant traumatic injury within 4 weeks of first study drug. * Use of St. John's Wort or rifampin (rifampicin). * Known or suspected allergy to sorafenib or any agent given in the course of this trial. * Any condition that impairs patient's ability to swallow whole pills.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients Needing a Dose Reduction. | participants were followed for an average of 25 months | The actual percentage was determined by taking the number of patients requiring a dose reduction divided by the total number of patients multiplied by100% |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Clinical Benefit (OCB)of This Combination as Calculated by the Sum of Complete Response (CR), Partial Response (PR), and Stable Disease (SD). | 3-10 months | Assessment of response was done per Response Evaluation Criteria in Solid Tumors (RECIST) criteria as outlined in the protocol. Complete Response (CR) defined as disappearance of all measurable lesions. Partial Response (PR) more than 30% decrease in the sum of longest diameter of measurable lesions compared to baseline. Stable Disease (SD) lesions should have no sufficient decrease for PR any sufficient increase to meet criteria for PD. Progressive Disease (PD) more than 20% increase in the sum of longest diameter of measurable lesions compared to baseline, and/or evidence of new lesions on imaging studies or the appearance of 2 or more new bony lesions. For patient with measurable disease,prostate-specific antigen (PSA), progression in the absence of measurable disease progression will not be considered progressive disease. Overall Clinical Benefit (OCB) (CR + PR+ SD)/#participants. |
| PSA -Biochemical Response | 1-10 months | PSA Biochemical Response = PSA complete response + PSA partial response. A PSA complete response is defined as a non-detectable PSA (\<4 ng/dl). A PSA partial response is defined as a PSA that decreases by greater than or equal to 50%. |
Countries
United States
Participant flow
Recruitment details
Recruitment was from our clinic population.
Pre-assignment details
Eligible patients were those who progressed while receiving chemotherapy (docetaxel or mitoxantrone)or within 12 weeks of stopping chemo.
Participants by arm
| Arm | Count |
|---|---|
| Single Agent Sorafenib Oral Single agent Sorafenib 400mg twice daily | 22 |
| Total | 22 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
Baseline characteristics
| Characteristic | Single Agent Sorafenib |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 17 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants |
| Region of Enrollment United States | 22 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 22 / 22 |
| serious Total, serious adverse events | 12 / 22 |
Outcome results
Primary
Percentage of Patients Needing a Dose Reduction.
The actual percentage was determined by taking the number of patients requiring a dose reduction divided by the total number of patients multiplied by100%
Time frame: participants were followed for an average of 25 months
Population: 15 patients required dose reductions.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Single Agent Sorafenib | Percentage of Patients Needing a Dose Reduction. | 71 percentage of participants |
Secondary
Overall Clinical Benefit (OCB)of This Combination as Calculated by the Sum of Complete Response (CR), Partial Response (PR), and Stable Disease (SD).
Assessment of response was done per Response Evaluation Criteria in Solid Tumors (RECIST) criteria as outlined in the protocol. Complete Response (CR) defined as disappearance of all measurable lesions. Partial Response (PR) more than 30% decrease in the sum of longest diameter of measurable lesions compared to baseline. Stable Disease (SD) lesions should have no sufficient decrease for PR any sufficient increase to meet criteria for PD. Progressive Disease (PD) more than 20% increase in the sum of longest diameter of measurable lesions compared to baseline, and/or evidence of new lesions on imaging studies or the appearance of 2 or more new bony lesions. For patient with measurable disease,prostate-specific antigen (PSA), progression in the absence of measurable disease progression will not be considered progressive disease. Overall Clinical Benefit (OCB) (CR + PR+ SD)/#participants.
Time frame: 3-10 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Single Agent Sorafenib | Overall Clinical Benefit (OCB)of This Combination as Calculated by the Sum of Complete Response (CR), Partial Response (PR), and Stable Disease (SD). | 76 percentage of patients |
Secondary
PSA -Biochemical Response
PSA Biochemical Response = PSA complete response + PSA partial response. A PSA complete response is defined as a non-detectable PSA (\<4 ng/dl). A PSA partial response is defined as a PSA that decreases by greater than or equal to 50%.
Time frame: 1-10 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Single Agent Sorafenib | PSA -Biochemical Response | 45 percentage of participants |