Prostate Cancer
Conditions
Keywords
Prostate Cancer
Brief summary
This is a clinical trial of orally administered Ruxolitinib (INCB018424) in patients whose disease has progressed following 1 prior chemotherapy regimen (not including anti-androgens or ketoconazole) for metastatic, androgen-independent prostate cancer.
Interventions
DRUGRuxolitinib
Ruxolitinib 25 mg tablets taken with water twice a day.
Sponsors
Incyte Corporation
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
* Diagnosed with radiographically-documented metastatic prostate cancer that has progressed while receiving androgen-suppressive therapy in the form of a bilateral orchiectomy or Gonadotropin-Releasing Hormone (GnRH) agonist (eg, leuprolide, goserelin). * Patients must demonstrate evidence of progressive disease based on 1 of the following criteria: 1) Progressive measurable disease, or 2) Progressive rise in prostate-specific antigen (PSA) level (2 consecutive rises from a prior reference level), or 3) Development of new lesions on bone scan. * If receiving a GnRH agonist as primary hormonal therapy, the serum testosterone level must be ≤ 50 ng/mL. * Must have received and progressed during or following 1 prior chemotherapy regimen for metastatic disease (not including an anti-androgen or ketoconazole); or, must have discontinued prior systemic therapy because of poor tolerance or other adverse effects; or, must have refused chemotherapy treatment. Patients having undergone more than 1 prior chemotherapy regimen may be admitted at the discretion of the sponsor. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. * Baseline serum PSA level of ≥ 10 ng/mL
Exclusion criteria
* Received any anti-cancer medications in the 30 days before receiving their first dose of study medication except for GnRH agonists and bisphosphonates. * Any unresolved toxicity greater than or equal to Grade 2 from previous anti-cancer therapy, except for stable chronic toxicities not expected to resolve, such as peripheral neurotoxicity.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a Prostate-specific Antigen Response | Assessed monthly from Baseline until the end of study (up to 8 months) | A prostate-specific antigen (PSA) response was defined as a PSA decline from Baseline of 50% or greater, repeated on 2 occasions at least 4 weeks apart. |
| Number of Participants With Adverse Events (AE) | From Baseline through to the end of study (up to 8 months) | A treatment-related AE was defined as an event with a definite, probable, or possible causality to study medication. A serious AE is an event resulting in death, hospitalization, persistent or significant disability/incapacity, or is life threatening, a congenital anomaly/birth defect or requires medical or surgical intervention to prevent 1 of the outcomes above. The intensity of an AE was graded according to the National Cancer Institute common terminology criteria for adverse events (NCI-CTCAE) version 3.0: Grade 1 (Mild); Grade 2 (Moderate); Grade 3 (Severe); Grade 4 (life-threatening). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Progression | From Baseline until the end of study (up to 8 months). | The time from first dosing day to the date of disease progression: * Progressive measurable disease by RECIST criteria (regardless of bone scan or prostate-specific antigen (PSA) results). * Development of unequivocal new lesions on bone scan without clinical suspicion of a flare reaction. * In patients who responded or had a decreased PSA from Baseline, a rise of 50% from PSA nadir, if the increase is ≥ 5 ng/mL or back to Baseline and confirmed by a 2nd value. * In patients with no decrease in PSA from Baseline, a 25% rise over Baseline and ≥ 5 ng/mL confirmed by a 2nd value. |
| Number of Participants With a Complete Response or Partial Response | From Baseline through the end of study (up to 8 months) | Complete Response (CR) and Partial Response (PR) defined by the Response Evaluation Criteria in Solid Tumor (RECIST) criteria. CR: Disappearance of all target and nontarget lesions. PR: At least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter, or persistence of 1 or more nontarget lesion(s) or/and maintenance of tumor marker level above the normal limits. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ruxolitinib Participants received ruxolitinib 25 mg orally twice daily in 12-hour intervals for 21-day cycles for as long as the study medication was tolerated and provided clinical benefit. | 22 |
| Total | 22 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Death | 2 |
| Overall Study | Disease progression | 15 |
| Overall Study | Physician Decision | 4 |
Baseline characteristics
| Characteristic | Ruxolitinib |
|---|---|
| Age, Continuous | 70.4 years STANDARD_DEVIATION 7.11 |
| 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 | 21 / 22 |
| serious Total, serious adverse events | 9 / 22 |
Outcome results
Primary
Number of Participants With Adverse Events (AE)
A treatment-related AE was defined as an event with a definite, probable, or possible causality to study medication. A serious AE is an event resulting in death, hospitalization, persistent or significant disability/incapacity, or is life threatening, a congenital anomaly/birth defect or requires medical or surgical intervention to prevent 1 of the outcomes above. The intensity of an AE was graded according to the National Cancer Institute common terminology criteria for adverse events (NCI-CTCAE) version 3.0: Grade 1 (Mild); Grade 2 (Moderate); Grade 3 (Severe); Grade 4 (life-threatening).
Time frame: From Baseline through to the end of study (up to 8 months)
Population: The Safety population included all enrolled patients who received at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ruxolitinib | Number of Participants With Adverse Events (AE) | Treatment-related adverse event | 16 Participants |
| Ruxolitinib | Number of Participants With Adverse Events (AE) | Serious adverse event | 9 Participants |
| Ruxolitinib | Number of Participants With Adverse Events (AE) | Any adverse event | 22 Participants |
| Ruxolitinib | Number of Participants With Adverse Events (AE) | Grade 3 or 4 adverse event | 13 Participants |
| Ruxolitinib | Number of Participants With Adverse Events (AE) | Discontinued study medication due to adverse event | 4 Participants |
| Ruxolitinib | Number of Participants With Adverse Events (AE) | Discontinued study due to adverse events | 1 Participants |
Primary
Number of Participants With a Prostate-specific Antigen Response
A prostate-specific antigen (PSA) response was defined as a PSA decline from Baseline of 50% or greater, repeated on 2 occasions at least 4 weeks apart.
Time frame: Assessed monthly from Baseline until the end of study (up to 8 months)
Population: The Intent-to-treat population, which included all patients enrolled in the study who took at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ruxolitinib | Number of Participants With a Prostate-specific Antigen Response | 0 participants |
Secondary
Number of Participants With a Complete Response or Partial Response
Complete Response (CR) and Partial Response (PR) defined by the Response Evaluation Criteria in Solid Tumor (RECIST) criteria. CR: Disappearance of all target and nontarget lesions. PR: At least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter, or persistence of 1 or more nontarget lesion(s) or/and maintenance of tumor marker level above the normal limits.
Time frame: From Baseline through the end of study (up to 8 months)
Population: According to the protocol, the sponsor decided to close the study after it was determined that less than 2 of the first 22 patients showed a PSA50 response. Given that all patients discontinued the study due to lack of efficacy, the secondary endpoint of tumor response rate was not assessed.
Secondary
Time to Progression
The time from first dosing day to the date of disease progression: * Progressive measurable disease by RECIST criteria (regardless of bone scan or prostate-specific antigen (PSA) results). * Development of unequivocal new lesions on bone scan without clinical suspicion of a flare reaction. * In patients who responded or had a decreased PSA from Baseline, a rise of 50% from PSA nadir, if the increase is ≥ 5 ng/mL or back to Baseline and confirmed by a 2nd value. * In patients with no decrease in PSA from Baseline, a 25% rise over Baseline and ≥ 5 ng/mL confirmed by a 2nd value.
Time frame: From Baseline until the end of study (up to 8 months).
Population: According to the protocol, the sponsor decided to close the study after it was determined that less than 2 of the first 22 patients showed a PSA50 response. Given that all patients discontinued the study due to lack of efficacy, the secondary endpoint of median time to progression was not assessed.