Clinical trial NCT00225420: Docetaxel, Androgen Ablation, and External-Beam Radiation Therapy in Patients With High-Risk Localized Prostate Cancer
Official title: A Phase I/II Study of Concurrent Weekly Docetaxel (Taxotere®), Androgen Ablation, and Adaptive External Beam Radiotherapy for Localized High-Risk Adenocarcinoma of the Prostate
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Prostate Cancer
Keywords: adenocarcinoma of the prostate
stage I prostate cancer
stage II prostate cancer
stage III prostate cancer
stage IV prostate cancer
Lead sponsor: UNC Lineberger Comprehensive Cancer Center
Sponsor class: OTHER
Collaborators: name: Sanofi
First posted: 2005-09-23
Enrollment: 23
Sex: MALE
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Patients Experiencing Dose-Limiting Toxicities
timeFrame: Average follow up of 2 years
Secondary outcomes:
measure: Biochemical Progression-free Survival (PFS)
timeFrame: Average follow up of 2 years
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
state: North Carolina
city: Raleigh
country: United States
facility: Rex Cancer Center at Rex Hospital
state: North Carolina
Study officials:
affiliation: UNC Lineberger Comprehensive Cancer Center
name: Young Whang, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: