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Paclitaxel and Carboplatin in Treating Patients With Metastatic Prostate Cancer That Has Not Responded to Hormone Therapy

Phase 2
Completed
Conditions
Prostate Cancer
Interventions
Registration Number
NCT00049257
Lead Sponsor
Jonsson Comprehensive Cancer Center
Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combining paclitaxel with carboplatin in treating patients who have metastatic prostate cancer that has not responded to hormone therapy.

Detailed Description

OBJECTIVES:

* Determine the prostate-specific antigen (PSA) response rate and time to PSA progression in patients with metastatic hormone-refractory prostate cancer treated with paclitaxel and carboplatin.

* Determine the objective response rate, time to measurable or evaluable disease progression, and overall survival in patients treated with this regimen.

* Determine the safety and toxicity of this regimen in these patients.

OUTLINE: This is an open-label study.

Patients receive paclitaxel IV on days 1, 8, and 15 and carboplatin IV on day 1. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Patients are followed every 4 weeks for 12 weeks and then every 2 months thereafter.

PROJECTED ACCRUAL: Approximately 60 patients will be accrued for this study.

Recruitment & Eligibility

Status
COMPLETED
Sex
Male
Target Recruitment
58
Inclusion Criteria
  • Patients must be informed of investigational nature of the study and written informed consent must be obtained prior to study entry

  • Patients >18 years of age

  • Patients with a histologic diagnosis of adenocarcinoma of the prostate

  • Patients must have metastatic disease with progression despite androgen ablation. Patients who have not undergone orchiectomy must continue LHRH analogues. For patients receiving LHRH analogues their testosterone level must be < 50ng/dL

  • Patients with bidimensionally measurable disease or bone metastases that is not progressive but who have a rising PSA are eligible

  • Patients with an ECOG performance status <2

  • Patients must have discontinued flutamide or nilutamide at least 4 weeks prior to the first day of treatment with evidence of progressive disease. Patients must have discontinued bicalutamide at least 6 weeks prior to registration with evidence of progressive disease

  • Patients with adequate hematological, renal, and hepatic function as defined by the following required laboratory values:

    • While blood cell count: > 3,000/mm3
    • Absolute granulocyte count: > 1,500/mm3
    • Platelets: > 100,000/mm3
    • Hemoglobin: > 8.5 g/dL
    • Total bilirubin: < 1.5 mg/dL
    • Serum creatinine: < 2.5 mg/dL
    • AST or ALT: < 2.5 x institutional upper limit of normal
  • Patients may have received prior radiation therapy, provided at least 4 weeks have elapsed since the conclusion of radiation therapy

Exclusion Criteria
  • Patients with biochemical only progression
  • Patients who have received any prior chemotherapy for cancer of the prostate
  • Patients who received antiandrogen therapy within 4 weeks prior to the first day of treatment after cessation of flutamide or nilutamide, and or within 6 weeks prior to registration after cessation of bicalutamide
  • Patients receiving concomitant chemotherapy, biologic therapy, or radiation therapy
  • Patients who have received Strontium 89 or other radioisotope therapies
  • Patients with decreasing PSA levels following antiandrogen withdrawal
  • Patients with > grade 1 peripheral sensory or motor neuropathy
  • Patients with known carcinomatous meningitis or brain metastases are excluded
  • Patients with past or current histories of neoplasm other than entry diagnosis except for in-situ carcinoma of any site, non-melanoma skin cancer, or other malignancy treated by surgery or radiation with a disease-free survival longer than 5 years
  • Patients who have undergone major surgery < 3 weeks prior to registration, except for biopsy or placement of a venous access device. Patients must have fully recovered from all effects of any prior surgery
  • Patients with histories of serious cardiac disease not adequately controlled: documented myocardial infarction within the last 6 months preceding registration, congestive heart failure, unstable angina, valvular disease with documented ventricular compromise, uncontrolled hypertension, arrhythmia uncontrolled by medication, clinically significant pericardial effusion
  • Patients with active serious infections or other serious underlying medical conditions that would otherwise impair their ability to receive protocol treatments
  • Patients with dementia or significantly altered mental status that would prohibit the understanding and/or giving of informed consent
  • Patients receiving other investigational therapy
  • Use of any investigational agent within 30 days of first day of treatment and use of Ketoconazole, hydrocortisone, glucocorticoids, or megace within 30 days of first day of treatment or other concomitant medications

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
TreatmentcarboplatinPlease see intervention descriptions
TreatmentpaclitaxelPlease see intervention descriptions
Primary Outcome Measures
NameTimeMethod
Time to PSA ProgressionEvaluated every 28 days during Treatment Period

In patients whose PSA has not decreased, progressive disease is a 25% increase over the baseline value and an increase in the absolute value PSA level by \>=5ng/ml, confirmed by a second value at \>=4 week intervals. In patients whose PSA has decreased but has not reached response criteria, progressive disease is defined as an increase in PSA by 25% over the nadir, provided that the increase is \>=5ng/ml and is confirmed by a second value at \>=4 week intervals.

Prostate-specific Antigen (PSA) Response RateEvaluated every 28 days during Treatment Period. Number of completed cycles among 58 treated patients range from 1 to 24 cycles with a median of 4.5 cycles. one cycle = 28 days.

PSA response is defined as a decline from the baseline value of \>=50% confirmed by a second PSA value 4 or more weeks later.

Secondary Outcome Measures
NameTimeMethod
Objective Response RateEvaluated every 12 weeks during Treatment Period

Complete response:Complete disappearance of all clinically detectable malignant disease for at least 4 weeks.Partial Response:Definite improvement in evaluable disease estimated to be in excess of 50% and agreed upon by 2 investigators. Response must last for at least 4 weeks.Stable disease:No significant change in disease for at least 4 weeks. Includes an estimated decrease of \<50% and lesions with an estimated increase of \<25%.Progressive disease(PD):Definite increase in area of any malignant lesion estimated to be \>=25% or appearance of new lesions. Need for radiotherapy is considered PD.

Overall Survival RateAssessed every two months after completion of study treatment for 4 years

Complete response:Complete disappearance of all clinically detectable malignant disease for at least 4 weeks.Partial Response:Definite improvement in evaluable disease estimated to be in excess of 50% and agreed upon by 2 investigators. Response must last for at least 4 weeks.Stable disease:No significant change in disease for at least 4 weeks. Includes an estimated decrease of \<50% and lesions with an estimated increase of \<25%.Progressive disease(PD):Definite increase in area of any malignant lesion estimated to be \>=25% or appearance of new lesions. Need for radiotherapy is considered PD.

Trial Locations

Locations (1)

Jonsson Comprehensive Cancer Center at UCLA

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Los Angeles, California, United States

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