Radiation Therapy and Ixabepilone in Treating Patients With High-Risk Stage III Prostate Cancer After Surgery

Study Overview
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Brief Summary
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RATIONALE: Radiation therapy uses high energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as ixabepilone, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Ixabepilone may also make tumor cells more sensitive to radiation therapy. Giving radiation therapy with chemotherapy after surgery may kill any tumor cells that remain after surgery. PURPOSE: This phase I/II trial is studying the side effects and best dose of ixabepilone when given together with radiation therapy to see how well it works in treating patients with high-risk stage III prostate cancer after surgery.

Detailed Description
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OBJECTIVES: Primary To determine the maximum-tolerated dose and dose-limiting toxicity of ixabepilone in combination with concurrent intensity-modulated radiation therapy in patients with high-risk prostate cancer after prostatectomy. (Phase I) To determine the toxicity profile of this regimen in these patients. (Phase I) Secondary To assess freedom from progression in patients treated with this regimen. (Phase II) To assess biochemical failure, local failure, and distant failure in patients treated with this regimen. (Phase II) To assess disease-specific survival and overall survival of patients treated with this regimen. (Phase II) To evaluate acute and late toxicity of this regimen in these patients. OUTLINE: This is a phase I, dose-escalation study of ixabepilone followed by a phase II study. Patients undergo adjuvant intensity-modulated radiation therapy once daily, 5 days a week, for 7-9 weeks. Patients also receive concurrent ixabepilone IV over 1 hour on days 1 and 8. Treatment with ixabepilone repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. After completion of study therapy, patients are followed up every 3 months for 1 year, every 6 months for 3 years, and then annually for 6 years.

Official Title
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A Phase I/II Study of Adjuvant Prostate Irradiation and Ixabepilone For High Risk Prostate Cancer Post-Prostatectomy

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: ixabepilone
* Procedure: adjuvant therapy
* Radiation: intensity-modulated radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of adenocarcinoma of the prostate Must have undergone any common form of prostatectomy (e.g., open, perineal, laparoscopic, or robotic) within the past 2 years T3 disease or positive surgical margins Node negative (N0) and free of distant metastasis (M0) by a bone scan and CT scan or MRI of the pelvis within the past 90 days Considered high-risk disease Gleason score = 7 and post-operative PSA > 0 and ≤ 2 ng/mL OR Gleason score ≥ 8 and post-operative PSA ≥ 0 and ≤ 2 ng/mL Pre-prostatectomy PSA available Range of pre-prostatectomy PSA values not required PATIENT CHARACTERISTICS: Zubrod (ECOG) performance status 0-1 ANC ≥ 2,000/mm^3 Platelet count ≥ 100,000/mm^3 Hemoglobin ≥ 8 g/dL Total bilirubin < 1.5 times upper limit of normal (ULN) AST and ALT < 2.5 times ULN Alkaline phosphatase < 2.5 times ULN Fertile patients must use effective contraception during and for 4 weeks after completion of study therapy Patients with urinary incontinence waiting for stabilization of urinary function after prostatectomy allowed for up to 6 months No CTCv4 peripheral neuropathy (motor or sensory) ≥ grade 1 No history of inflammatory colitis including Crohn disease or ulcerative colitis No significant history of psychiatric illness No other invasive malignancy within the past 3 years except adequately treated nonmelanoma skin cancer or carcinoma in situ of the oral cavity No severe, active co-morbidity with any of the following: Unstable angina and/or congestive heart failure requiring hospitalization within the past 6 months Transmural myocardial infarction within the past 6 months Acute bacterial or fungal infection requiring IV antibiotics Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days Immunocompromised patients or AIDS based upon current CDC definition HIV testing not required No history of hypersensitivity reactions to agents containing Cremophor® EL or its derivatives (e.g., polyoxyethylated castor oil) PRIOR CONCURRENT THERAPY: See Disease Characteristics No prior pelvic radiotherapy or radiotherapy for another malignancy that encompasses ≥ 30% of major bone marrow-containing areas (e.g., pelvis or lumbar spine) No prior hormonal therapy for prostate cancer Prior hormonal agents, e.g., finasteride or dutasteride, for benign prostatic hypertrophy allowed No other concurrent adjuvant antineoplastic therapy planned while on this protocol, including the following: Cryotherapy Hormonal therapy Other chemotherapy for prostate cancer Prior chemotherapy for a different type of cancer allowed provided it was administered > 3 years ago

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ixabepilone<br>Adjuvant therapy | Drug: ixabepilone<br> <br> Procedure: adjuvant therapy<br> <br> Radiation: intensity-modulated radiation therapy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-limiting toxicity (phase I) | Dose-limiting toxicity (phase I) | 3 years | 
| Maximum-tolerated dose (phase I) | Maximum-tolerated dose (phase I) | 3 years | 
| Freedom from progression for 3 years (phase II) | Freedom from progression for 3 years (phase II) | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to biochemical, local and distant failure (phase II) | Time to biochemical, local and distant failure (phase II) | 3 years | 
| Disease-specific survival (phase II) | Disease-specific survival (phase II) | 3 years | 
| Overall survival rate (phase II) | Overall survival rate (phase II) | 3 years | 
| Adverse events as assessed by NCI CTCAE v. 4.0 | Adverse events as assessed by NCI CTCAE v. 4.0 | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adenocarcinoma of the prostate, stage III prostate cancer