Prostate Cancer
Conditions
Keywords
adenocarcinoma of the prostate, stage I prostate cancer, stage II prostate cancer, stage III prostate cancer, stage IV prostate cancer
Brief summary
RATIONALE: Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Androgens can cause the growth of prostate cancer cells. Antihormone therapy, such as leuprolide, may lessen the amount of androgens made by the body. Radiation therapy uses high energy x-rays to kill tumor cells. Giving docetaxel together with androgen ablation therapy and external-beam radiation therapy may kill more tumor cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of docetaxel when given together with androgen ablation therapy and external-beam radiation therapy and to see how well they work in treating patients with high-risk localized prostate cancer.
Detailed description
OBJECTIVES: Primary * Determine the dose-limiting toxicity and maximum tolerated dose of docetaxel when administered in combination with androgen ablation therapy and adaptive external-beam radiotherapy in patients with high-risk localized adenocarcinoma of the prostate. Secondary * Determine the 2-year biochemical progression-free survival of patients treated with this regimen. OUTLINE: This is a multicenter, open-label, dose-escalation study of docetaxel. * Androgen ablation therapy: Patients receive leuprolide acetate or other luteinizing hormone-releasing hormone agonist beginning 2-3 months prior to the start of chemoradiotherapy and continuing for up to 2 years. * Chemoradiotherapy: Patients receive docetaxel IV over 1 hour on day 1 and high-dose external-beam radiotherapy on days 1-5. Treatment repeats every 7 days for 8 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of docetaxel until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. After completion of study treatment, patients are followed every 3 months.
Interventions
DRUGdocetaxel
Docetaxel will be administered per the designated cohort starting at 10 mg/m2 intravenously over 1 hour weekly for eight weeks, for a total of eight treatments.
DRUGleuprolide acetate
Leuprolide acetate will be administered at 22.5 mg IM and will be initiated 2 to 3 months prior to radiotherapy and chemotherapy with docetaxel.
RADIATIONradiation therapy
The total dose will be 7800 cGy in 200 centigray (cGy) per fraction for a total of 39 treatments.
Sponsors
Sanofi
UNC Lineberger Comprehensive Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
1. Histologically confirmed adenocarcinoma of the prostate with any of following clinical features: A) T3 or T4 B) T1-2 + Gleason Score 8-10 C) T1-2 + Gleason Score 7 + Prostate Specific Antigen (PSA) \>10 ng/mL D) T1-2 + Any Gleason Score + PSA \>20 ng/mL 2. No evidence of metastatic disease on chest x-ray, bone scan or CT scan of abdomen/pelvis. 3. Age \> 18 4. The Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 5. Peripheral neuropathy: must be \< grade 1 6. Hematologic parameters A) Absolute neutrophil count \> 1,500/mm3 B) Hemoglobin \> 8.0 g/dL C) Platelet count \> 100,000/mm3. 7. Hepatic parameters / Renal function A) Total Bilirubin must be ≤ 1.2 mg/dL B) Transaminases (AST and ALT) must be \< 1.5 x upper limit of normal (ULN) C) Alkaline phosphatase must be \< 2.5 x ULN D) Creatinine \< 1.5 x ULN ( \< 2.1 mg/dL) 8. No prior pelvic or prostate radiation or chemotherapy for prostate cancer. Androgen ablation therapy with one of the luteinizing hormone-releasing hormone (LH-RH) agonists prior to enrollment is acceptable as long as protocol treatment with radiotherapy and chemotherapy is started within 3 months of the initiation of androgen ablation. 9. Patient must be willing to consent to using effective contraception while on treatment and for at least 3 months thereafter.
Exclusion criteria
1. Documented metastases on staging studies 2. Life expectancy \<10 years secondary to co-morbid illness 3. Myocardial infarction or significant change in anginal pattern within one year prior to study entry or current congestive heart failure (New York Heart Association Class 2 or higher) 4. Patients with a history of severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80 5. History of invasive malignancy within the last five years prior to study entry except for carcinoma in situ or nonmelanoma skin cancer. 6. Psychiatric conditions which would prevent compliance with treatment or adequate informed consent. 7. Patients receiving another investigational agent during chemo- and radiotherapy 8. Uncontrolled intercurrent illness or other conditions that limit compliance with protocol treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Experiencing Dose-Limiting Toxicities | Average follow up of 2 years | Determine the number of patients experiencing dose-limiting toxicities (DLT) at each dose level. DLT was defined as grade 3-4 non-haematological or grade 4 haematological toxicity, using the Common Terminology Criteria for Adverse Events, version 3.0. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Biochemical Progression-free Survival (PFS) | Average follow up of 2 years | Measure of the activity of a treatment on a disease. In this study it is measured from the date of enrollment to the date on which the prostate cancer progresses or the date the patient dies. Survival curves were estimated using the Kaplan-Meier technique. Biochemical (PSA) failure is defined, in accordance to the American Society for Therapeutic Radiology and Oncology consensus definition, as three consecutive rise in PSA. The date of biochemical failure is considered to be the midpoint between the last non-rising PSA and the first rising PSA. |
Countries
United States
Participant flow
Recruitment details
Subjects with high-risk or locally advanced prostate cancer were recruited from 2 institutions between December 2005 and January 2010.
Pre-assignment details
Two patients were taken off the study due illness, two were removed because they were too large for the equipment, and one was removed due to CT screen failure.18 men with high-risk or locally advanced prostate cancer were enrolled. All 18 patients completed their radiation therapy and 16 completed all planned chemotherapy doses.
Participants by arm
| Arm | Count |
|---|---|
| Overall Study Single Arm Docetaxel: Docetaxel will be administered per the designated cohort starting at 10, 15 or 20 mg/m2 intravenously over 1 hour weekly for eight weeks, for a total of eight treatments.
leuprolide acetate: Leuprolide acetate will be administered at 22.5 mg IM and will be initiated 2 to 3 months prior to radiotherapy and chemotherapy with docetaxel.
radiation therapy: The total dose will be 7800 cGy in 200 cGy per fraction for a total of 39 treatments. | 18 |
| Total | 18 |
Baseline characteristics
| Characteristic | Overall Study |
|---|---|
| Age, Continuous | 62 years |
| Clinical Stage T1c-T2a | 9 Participants |
| Clinical Stage T2b-T2c | 5 Participants |
| Clinical Stage T3 | 4 Participants |
| Gleason Score Grade 7 | 3 Participants |
| Gleason Score Grade 8-10 | 15 Participants |
| PSA level, ng/mL >100 ng/mL | 3 Participants |
| PSA level, ng/mL 10-19 ng/mL | 4 Participants |
| PSA level, ng/mL <10 ng/mL | 6 Participants |
| PSA level, ng/mL 20-100 ng/mL | 5 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 14 Participants |
| Region of Enrollment United States | 18 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 18 |
| other Total, other adverse events | 18 / 18 |
| serious Total, serious adverse events | 0 / 18 |
Outcome results
Primary
Number of Patients Experiencing Dose-Limiting Toxicities
Determine the number of patients experiencing dose-limiting toxicities (DLT) at each dose level. DLT was defined as grade 3-4 non-haematological or grade 4 haematological toxicity, using the Common Terminology Criteria for Adverse Events, version 3.0.
Time frame: Average follow up of 2 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Docetaxel at 10 mg/m2 | Number of Patients Experiencing Dose-Limiting Toxicities | 1 Participants |
| Docetaxel 15 mg/m2 | Number of Patients Experiencing Dose-Limiting Toxicities | 1 Participants |
| Docetaxel 20 mg/m2 | Number of Patients Experiencing Dose-Limiting Toxicities | 0 Participants |
Secondary
Biochemical Progression-free Survival (PFS)
Measure of the activity of a treatment on a disease. In this study it is measured from the date of enrollment to the date on which the prostate cancer progresses or the date the patient dies. Survival curves were estimated using the Kaplan-Meier technique. Biochemical (PSA) failure is defined, in accordance to the American Society for Therapeutic Radiology and Oncology consensus definition, as three consecutive rise in PSA. The date of biochemical failure is considered to be the midpoint between the last non-rising PSA and the first rising PSA.
Time frame: Average follow up of 2 years
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Docetaxel at 10 mg/m2 | Biochemical Progression-free Survival (PFS) | 94 percentage of patients |