Intensity-Modulated Radiation Therapy, Docetaxel, and Hormone Therapy in Treating Patients With High-Risk Locally Advanced Prostate Cancer With Pelvic Lymph Node Metastasis

Phase I Study Evaluating Extended Field Intensity Modulated Radiation Therapy and Docetaxel in Patients With Prostate Cancer Associated With Pelvic Node Metastasis

RATIONALE: Specialized radiation therapy that delivers a high- dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. 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 goserelin and bicalutamide, may lessen the amount of androgens made by the body. Giving radiation therapy together with chemotherapy and hormone therapy may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of docetaxel when given together with intensity-modulated radiation therapy and hormone therapy in treating patients with high-risk locally advanced prostate cancer with pelvic lymph node metastasis.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: docetaxel; Drug: bicalutamide; Drug: goserelin; Radiation: intensity-modulated radiation therapy

Detailed Description

OBJECTIVES:

Primary

• Determine, preliminarily, the grade III or IV toxicity rate of concurrent extended-field intensity-modulated radiotherapy (IMRT), docetaxel, and androgen deprivation therapy in patients with high-risk, locally advanced prostate cancer with pelvic lymph node metastasis.

Secondary

• Determine, preliminarily, the progression-free survival of patients treated with this regimen.
• Determine the maximum tolerated dose of docetaxel when administered with concurrent IMRT in this patients.

OUTLINE: This is a dose-escalation study of docetaxel.

Patients receive combined androgen deprivation therapy (if not already on combined hormonal therapy) comprising goserelin acetate* subcutaneously once every 3 months for up to 2 years and oral bicalutamide once daily beginning on day 1 and continuing until the completion of radiotherapy. Beginning at approximately week 9 of androgen deprivation therapy, patients receive docetaxel IV over 1 hour once weekly for up to 9 weeks. Concurrently with chemotherapy, patients undergo intensity-modulated radiotherapy 5 days a week for up to 45 fractions (9 weeks).

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.

NOTE: *Not required for patients who have undergone bilateral orchiectomy

After completion of study therapy, patients are followed periodically for 5 years.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Nebraska
    • Omaha, Nebraska, United States, 68198-6805
      • UNMC Eppley Cancer Center at the University of Nebraska Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the prostate

  • Locally advanced disease (T1 -T3b, N1 or N2, M0) at high risk for recurrence

    • Biopsy-proven pelvic lymph node involvement
    • No T4 lesion

• Prior androgen suppression within the past 14 months is allowed provided the following criterion is met:

  • No biochemical evidence of PSA progression after androgen withdrawal

    • PSA progression, defined as 2 consecutive rising PSA values > 4.0 ng/mL taken ≥ 2 weeks apart

• No evidence of distant metastasis, including any of the following:

  • Bone metastasis
  • Pathologic or radiographic evidence of lymph node involvement above the L4 - L5 interspace

PATIENT CHARACTERISTICS:

• Karnofsky performance status 80-100%
• ANC ≥ 1,500/mm³
• Hemoglobin ≥ 10 g/dL
• Platelet count > 100,000/mm³
• Bilirubin normal
• Fertile patients must use effective contraception during and for ≥ 3 months after completion of study treatment

• Meets 1 of the following criteria:

  • Alkaline phosphatase (AP) normal AND AST or ALT ≤ 5 times upper limit of normal (ULN)
  • AP ≤ 2.5 times ULN AND AST or ALT ≤ 1.5 times ULN
  • AP ≤ 5 times ULN AND AST or ALT normal
• No peripheral neuropathy > grade 1
• No significant comorbidity that would preclude radiotherapy
• No other prior malignancy except nonmelanoma skin cancer or any other cancer for which the patient has been disease-free for the past 5 years
• No hypersensitivity to docetaxel or other drugs formulated with polysorbate 80
• No history of Crohn's disease, ulcerative colitis, or irritable bowel syndrome
• No unrepaired inguinal hernia

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No prior pelvic or abdominal radiotherapy or prostate brachytherapy implant
• No prior prostatectomy
• No prior pelvic or abdominal surgery that resulted in excessive amounts of small intestine located within the pelvis
• No other concurrent investigational agents

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Toxicity rate as assessed by NCI CTCAE v3.0	during therapy and follow-up visits to continue for 5 years after radiation is completed

Secondary Outcome Measures

Outcome Measure	Time Frame
Progression-free survival	time to Prostate Specific Antigen (PSA) failure
Maximum tolerated dose (MTD) of docetaxel	Trial stopped: dose below which excess DLT observed. If 3 patients treated at that dose, then added 3 should be entered, that process proceeds down, so MTD becomes highest dose where no more than 1 toxicity observed in 6 patients.

Collaborators and Investigators

• Sponsor: University of Nebraska
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Ralph Hauke, MD, University of Nebraska; Study Chair: Elizabeth C. Reed, MD, University of Nebraska

Study record dates

Study Major Dates

• Study Start: August 1, 2004
• Primary Completion (Actual): March 1, 2010
• Study Completion (Actual): March 1, 2010

Study Registration Dates

• First Submitted: June 4, 2007
• First Submitted That Met QC Criteria: June 4, 2007
• First Posted (Estimate): June 5, 2007

Study Record Updates

• Last Update Posted (Actual): February 26, 2018
• Last Update Submitted That Met QC Criteria: February 22, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Keywords: stage III prostate cancer; stage IV prostate cancer; recurrent prostate cancer; adenocarcinoma of the prostate; stage I prostate cancer; stage II prostate cancer
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Androgen Antagonists; Docetaxel; Goserelin; Bicalutamide
• Other Study ID Numbers: 195-04; P30CA036727 (U.S. NIH Grant/Contract); UNMC-19504