Clinical trial NCT00669162: Postoperative Radiation Therapy, Hormonal Therapy and Concurrent Docetaxel for High Risk Pathologic Prostate Cancer
Official title: A Phase I/II Trial of Post-Prostatectomy Radiation Therapy, Hormonal Therapy and Concurrent Docetaxel for High Risk Pathologic T2-T3NO (Tumor-3, Node-0) Prostate Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Prostate Cancer
Lead sponsor: University of Kansas Medical Center
Sponsor class: OTHER
First posted: 2008-04-29
Enrollment: 27
Sex: MALE
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Following a radical prostatectomy and lymph node sampling, eligible patients will undergo post-operative radiation therapy, concurrent weekly docetaxel chemotherapy , and hormonal therapy (Casodex daily and Zoladex every 3 months for 2 times or Lupron 22.5 mg im every 3 months for 2 times).

Detailed description: After consent, laboratory and radiologic tests will be done and a baseline questionnaire will be completed. Participants will then be started on the protocol specific hormonal therapy for a total of 6 months. After 2 months of hormone therapy the participants will begin radiation therapy and concurrent docetaxel chemotherapy treatments.

The radiation therapy will be delivered to a total dose of 66.0 Gy at 2.0 Gy/fraction (fx) once daily over 7 weeks, using either a 3-D conformal technique and/or intensity modulated radiation therapy (IMRT).

Participants will receive docetaxel once a week for a total of 7 infusions with concurrent radiation therapy treatments. The weekly dose of docetaxel will be 20 mg/m2. Docetaxel will be given as an intravenous (IV) infusion over 30 minutes within ≤6 hours prior to the radiotherapy treatments.

Eligibility criteria: Inclusion Criteria:

* Only those patients with adenocarcinoma of the prostate who have undergone a radical prostatectomy with pelvic lymph node sampling and found to have high risk non-metastatic disease with undetectable, persistent or decreasing post-operative Prostate Specific Antigen (PSA) levels, or who have subsequently experienced a rise in PSA, will be eligible for the trial as described below in the inclusion and exclusion criteria
* Histologically documented adenocarcinoma of the prostate.
* Status post radical prostatectomy with sampling of the pelvic lymph nodes with histologically confirmed adenocarcinoma of the prostate, with the patients falling into either the "adjuvant high risk group" or the "salvage high risk group" as follows:

  * a) "Adjuvant High Risk Group" (undetectable, persistent or decreasing PSA levels before starting therapy) who have NO evidence of metastatic disease (i.e. no clinical symptoms or radiologic evidence) who MUST be able to start RT treatments within 6 months of radical prostatectomy with at least one of the 3 disease features:

    1. Pathologic tumor 2-node 0 (T2N0) disease with positive margins and Gleason score ≥8, or
    2. Pathologic tumor 3a-node 0 T3aN0 disease with extracapsular extension and Gleason Score ≥ 8, or
    3. Pathologic tumor 3b-node 0 T3bN0 disease with any Gleason Score
  * b) "Salvage High Risk Group" are those patients with PSA biochemical failure defined by 2 consecutive increases over baseline PSA levels at least one month apart, who have NO other evidence of metastatic disease (i.e. no clinical symptoms or radiologic evidence), and WITH AT LEAST ONE of the high risk disease features as defined below:

    1. Pathologic T3bN0 disease with any Gleason score, or
    2. Pathologic T2-3aN0 disease with Gleason score ≥ 8,
    3. Pathologic T2-3aN0 disease with PSA doubling time ≤10 months, or
    4. Pathologic T2-3aN0 disease with Pre-radiation therapy PSA level ≥1.0 ng/ml
* Neoadjuvant hormonal therapy prior to radical prostatectomy is allowed, and post-prostatectomy hormonal therapy is allowed as long as it is not within 6 months of protocol treatment
* No prior chemotherapy, or pelvic irradiation
* Karnofsky Performance Status ≥70
* Hematologic parameters must be within the following limits:

  * white blood cell count (WBC) ≥ 3,000
  * Platelet Count ≥ 130,000/ mm3
  * Hemoglobin level ≥ 11.0 g/dl
  * Creatinine ≤ 2.5 g/dl
* Normal liver function defined as the following: Total bilirubin below the upper limit of normal AND AST, ALT, and Alkaline Phosphatase must be within a defined range of eligibility as noted below:

  * Alkaline Phosphatase

    * ≤ ULN - eligible
    * \> 1x but ≤1.5x ULN - eligible
    * \> 2.5x but ≤ 5x ULN - eligible
    * \> 5x ULN - ineligible
  * aspartate aminotransferase (AST) or Alanine Aminotransferase (ALT)

    * ≤ upper limit of normal (ULN) - eligible
    * \> 1x but ≤1.5x ULN - eligible
    * \> 2.5x but ≤ 5x ULN - ineligible
    * \> 5x ULN - ineligible
* Patients with a history of an invasive malignancy within the last 5 years are not eligible for the protocol. Patients with history of benign tumors such as a pituitary macroadenomas, meningiomas, or craniopharyngiomas are eligible as long as the benign tumor is under local control regardless of the time frame. Patients with concurrent adequately treated basal cell or squamous cell carcinoma of the skin are also eligible for the protocol.
* Patients must be informed of the investigative nature of the treatment, must give appropriate informed consent to protocol procedures and must sign an Informed Consent Documentation Form.
* Must not have concomitant medical, psychological or social circumstances which would interfere with compliance with the protocol treatment and follow-up.
* Age ≥ 18 years
* Men of childbearing potential must be willing to consent to using effective contraception while on treatment and for a reasonable period thereafter, which should be for at least 6 months after the completion of protocol therapy

Exclusion Criteria:

* Patients who have received prior chemotherapy, pelvic irradiation or post-prostatectomy androgen ablation within 6 months of protocol therapy.
* Any coexisting medical condition precluding full compliance with the study.
* Patients with active infections or known infection with HIV.
* Psychological, familiar, sociological or geographical conditions which would not permit compliance with the study protocol.
* Known contraindication to dexamethasone (allergic reaction or systemic fungal infection)
* Pre-existing Grade ≥ 1 peripheral neuropathy
* Patients with a history of a hypersensitivity reaction to products containing Polysorbate 80 (Tween 80)

Primary outcomes:
measure: Percentage of Patients Who Can Safely Tolerate and Complete Adjuvant Hormonal Therapy, Radiation Therapy and Docetaxel After a Radical Prostatectomy
timeFrame: 8 Months
Secondary outcomes:
Other outcomes:
Locations:
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
Study officials:
affiliation: University of Kansas Medical Center
name: Xinglei Shen, MD
role: PRINCIPAL_INVESTIGATOR
References: