Clinical trial NCT01079793: Radiation Therapy and Ixabepilone in Treating Patients With High-Risk Stage III Prostate Cancer After Surgery
Official title: A Phase I/II Study of Adjuvant Prostate Irradiation and Ixabepilone For High Risk Prostate Cancer Post-Prostatectomy
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: Prostate Cancer
Keywords: adenocarcinoma of the prostate
stage III prostate cancer
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2010-03-03
Enrollment: 0
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: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Dose-limiting toxicity (phase I)
timeFrame: 3 years
measure: Maximum-tolerated dose (phase I)
timeFrame: 3 years
measure: Freedom from progression for 3 years (phase II)
timeFrame: 3 years
Secondary outcomes:
measure: Time to biochemical, local and distant failure (phase II)
timeFrame: 3 years
measure: Disease-specific survival (phase II)
timeFrame: 3 years
measure: Overall survival rate (phase II)
timeFrame: 3 years
measure: Adverse events as assessed by NCI CTCAE v. 4.0
timeFrame: 3 years
Other outcomes:
Locations:
city: Dallas
country: United States
facility: Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
state: Texas
Study officials:
affiliation: Simmons Cancer Center
name: David A. Pistenmaa, MD
role: PRINCIPAL_INVESTIGATOR
References: