Prostate Cancer
Conditions
Keywords
prostate
Brief summary
The purpose of this study is to determine the effectiveness of two drugs, docetaxel and Gleevec®(also called imatinib), in prostate cancer that no longer responds to hormone therapy. The investigators are interested in finding out if the combination of these two drugs is more effective than docetaxel alone in the treatment of prostate cancer.
Detailed description
This is a non-randomized multicenter Phase II trial of Gleevec and docetaxel in chemo naïve metastatic hormone refractory prostate cancer. The primary objective of this study is to assess the time to disease progression in patients with hormone refractory prostate cancer treated with daily oral imatinib and intravenous docetaxel, administered every three weeks. Secondary objectives include: 1) to assess the rate of response to imatinib and docetaxel, using Prostate Specific Antigen (PSA) and/or measurable disease; 2) to assess the overall survival of patients with hormone refractory prostate cancer treated with imatinib and docetaxel; and 3) to evaluate the qualitative and quantitative toxicities of this combination.
Interventions
DRUGGleevec
Imatinib-400mg po qd for 10 days to commence on day 3. On day 0, Docetaxel 60mg/m\^2 administered IV
DRUGDocetaxel
60 mg/m\^2 administered IV on day 0
Sponsors
Novartis Pharmaceuticals
Leonard Appleman
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
1. Must have a histologic diagnosis of adenocarcinoma of the prostate Stage D2 that is unresponsive or refractory to hormone therapy. Must have metastatic prostate cancer with a rising PSA, and deemed to be hormone refractory. 2. All subjects must have pre-study PSA within 28 days prior to registration 3. Subjects who have measurable disease must have had X-rays, scans or physical examinations used for tumor measurement completed within 28 days prior to registration. Subjects must have non-measurable disease assessed within 28 days (for PSA level) or 42 days (for imaging studies) prior to registration. 4. Subjects with bone metastases, as documented by X-ray, bone scan, MRI, or biopsy. 5. All subjects must have had a CT scan of the abdomen and pelvis within 28 days prior to registration. 6. Subjects must have been surgically or medically castrated. If the method of castration was LHRH (Luteinizing Hormone-Releasing Hormone) agonists, then the subject must be willing to continue the use of LHRH agonists. 7. If the subject has been treated with non-steroidal anti-androgens or other hormonal treatment these agents must have been stopped at least 28 days prior to enrollment for flutamide or ketoconazole, and at least 42 days prior to enrollment for bicalutamide or nilutamide; and the subjects must have demonstrated progression of disease since the agents were suspended. 8. Prior radiation therapy is allowed. At least 21 days must have elapsed since the completion of radiation therapy, and the subject must have recovered from the side effects of the radiation 9. 9\. Due to the unknown side effects of imatinib, men of reproductive potential must agree to use an effective contraceptive method. 10. Subjects must have recovered from major infections and/or surgical procedures and, in the opinion of the investigator, not have significant active concurrent other medical illness precluding protocol treatment. 11. ECOG performance status of 0-1 12. ANC ≥ 1,500/mL and a platelet count of ³ 100,000/mL. These tests must be obtained within 7 days prior to registration. 13. Serum bilirubin ≤ 1.3, SGOT and SGPT ≤ 2 x institutional upper limit of normal, and a serum creatinine ≤ 1.8 mg/dl. These tests must be obtained within 7 days prior to registration. Testosterone level may be done 28 days prior to study entry. Testosterone level should be below 50 ng/dL.
Exclusion criteria
1. No prior chemotherapy for hormone-refractory disease is allowed. At least three weeks must have elapsed since the completion of any non-cytotoxic investigational therapy, and the patient must have recovered from the side effects of the therapy. 2. No other cytotoxics, biological response modifiers, radiation therapy, corticosteroid or hormonal concomitant therapy (other than continuing LHRH treatment) may be given during protocol treatment. Bisphosphonates may be given during protocol treatment. No unconventional therapy may be given during protocol treatment. 3. Subjects must NOT have Grade III/IV cardiac problems as defined by the New York Heart Association Criteria. 4. Subjects with known chronic liver disease are NOT eligible 5. Must NOT have a known diagnosis of human immunodeficiency virus (HIV) infection. 6. Subjects must NOT have known brain metastases. 7. No prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ carcinoma of any site, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for 5 years.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Time To Progression (TTP) | Up to 24 months | TTP is the amount of time from date of registration to date of first documentation of progression or symptomatic deterioration. For progression, one or more of the following must occur: (1) 20% increase in the sum of longest diameters of target measurable lesions over smallest sum observed (over baseline if no decrease during therapy) using the same techniques as baseline. (2) Increase in PSA by at least 25% from baseline in patients whose PSA did not decrease, and of 50% from nadir in patients whose PSA decreased with a confirmation 3 weeks later. (3) Unequivocal progression of non-measurable disease in the opinion of the treating physician (an explanation must be provided). (4) Appearance of any new lesion/site. (5) Death due to disease without prior documentation of progression and without symptomatic deterioration, which is defined as global deterioration of health status requiring discontinuation of treatment without objective evidence of progression. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Prostate-Specific Antigen (PSA) Response Rate | Up to 12 months | PSA response rate is the number of participants who experienced a best response of: complete response, CR (PSA less than or equal to 0.2 ng/mL, documented two or more times, a minimum of four weeks apart), partial response, PR (a decline in PSA by at least 50%, confirmed by a second PSA value four or more weeks later) or stable disease (does not qualify for CR, PR, Progression or Symptomatic Deterioration, at least 6 weeks after registration) / total number of analyzable patients. |
| Overall Survival (OS) | Up to 60 months | OS is the amount of time in months from the date of registration to the date of death from any cause. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Hormone Refractory Prostate Cancer Patients Docetaxel 60 mg/m\^2 IV every 21 days + Imatinib 400 mg PO daily, or, for 10/21 days | 49 |
| Total | 49 |
Baseline characteristics
| Characteristic | Hormone Refractory Prostate Cancer Patients |
|---|---|
| Age, Continuous | 69 years |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 49 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 48 / 49 |
| serious Total, serious adverse events | 35 / 49 |
Outcome results
Primary
Overall Time To Progression (TTP)
TTP is the amount of time from date of registration to date of first documentation of progression or symptomatic deterioration. For progression, one or more of the following must occur: (1) 20% increase in the sum of longest diameters of target measurable lesions over smallest sum observed (over baseline if no decrease during therapy) using the same techniques as baseline. (2) Increase in PSA by at least 25% from baseline in patients whose PSA did not decrease, and of 50% from nadir in patients whose PSA decreased with a confirmation 3 weeks later. (3) Unequivocal progression of non-measurable disease in the opinion of the treating physician (an explanation must be provided). (4) Appearance of any new lesion/site. (5) Death due to disease without prior documentation of progression and without symptomatic deterioration, which is defined as global deterioration of health status requiring discontinuation of treatment without objective evidence of progression.
Time frame: Up to 24 months
Population: Patients with hormone refractory prostate cancer who received at least 1 cycle of Docetaxel + Imatinib
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Hormone Refractory Prostate Cancer Patients | Overall Time To Progression (TTP) | 6.4 months |
Secondary
Overall Survival (OS)
OS is the amount of time in months from the date of registration to the date of death from any cause.
Time frame: Up to 60 months
Population: Patients with hormone refractory prostate cancer who received at least 1 cycle of Docetaxel + Imatinib
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Hormone Refractory Prostate Cancer Patients | Overall Survival (OS) | 23.1 months |
Secondary
Prostate-Specific Antigen (PSA) Response Rate
PSA response rate is the number of participants who experienced a best response of: complete response, CR (PSA less than or equal to 0.2 ng/mL, documented two or more times, a minimum of four weeks apart), partial response, PR (a decline in PSA by at least 50%, confirmed by a second PSA value four or more weeks later) or stable disease (does not qualify for CR, PR, Progression or Symptomatic Deterioration, at least 6 weeks after registration) / total number of analyzable patients.
Time frame: Up to 12 months
Population: Patients with hormone refractory prostate cancer who received at least 1 cycle of Docetaxel + Imatinib
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Hormone Refractory Prostate Cancer Patients | Prostate-Specific Antigen (PSA) Response Rate | 72.4 percentage of patients |