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

• Sponsor: Jonsson Comprehensive Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00049257
• Collaborator: Bristol-Myers Squibb (Industry)
• Enrollment: 58
• Location: 1
• Arm: 1
• Duration (Months): 77
• Patients Per Site Per Month: 0.8

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Drug: carboplatin; Drug: paclitaxel	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 58 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Trial of Paclitaxel and Carboplatin in the Treatment of Hormone-Refractory Prostate Cancer (HRPC)
• Study Start Date: Oct 1, 2002
• Actual Primary Completion Date: Mar 1, 2009
• Actual Study Completion Date: Mar 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment Please see intervention descriptions	Drug: carboplatin; Administered Day 1 of each cycle. AUC=6.; Other Names: Paraplatin ; Drug: paclitaxel; administered Days 1, 8, and 15 of each cycle. 100mg/m2; Other Names: Taxol

Outcome Measures

Primary Outcome Measures

1. Prostate-specific Antigen (PSA) Response Rate [Evaluated 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.

2. Time to PSA Progression [Evaluated 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.

Secondary Outcome Measures

1. Objective Response Rate [Evaluated 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.

2. Overall Survival Rate [Assessed 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Jonsson Comprehensive Cancer Center at UCLA	Los Angeles	California	United States	90095-1781

Sponsors and Collaborators

• Jonsson Comprehensive Cancer Center
• Bristol-Myers Squibb

Investigators

• Principal Investigator: Fairooz F. Kabbinavar, MD, Jonsson Comprehensive Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jonsson Comprehensive Cancer Center
• ClinicalTrials.gov Identifier: NCT00049257
• Other Study ID Numbers: CDR0000258050; UCLA-0202092; BMS-UCLA-020209201; NCI-G02-2121
• First Posted: Jan 27, 2003
• Last Update Posted: Sep 1, 2020
• Last Verified: Aug 1, 2012

• Keywords provided by Jonsson Comprehensive Cancer Center: adenocarcinoma of the prostate; recurrent prostate cancer; stage IV prostate cancer
• Additional relevant MeSH terms: Prostatic Neoplasms; Paclitaxel; Carboplatin

Study Results

Participant Flow

Recruitment Details	Date of recruitment period: 10/02/2002- 5/25/2006. Types of location: Academic Medical clinics and community medical clinics. This study has 1 treatment arm; therefore randomization procedures were not utilized and all participants were enrolled to the same treatment regimen.

Arm/Group Title	Carboplatin, Paclitaxel
Arm/Group Description	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.
Period Title: Carboplatin, Paclitaxel
STARTED	58
COMPLETED	45
NOT COMPLETED	13
Period Title: Carboplatin, Paclitaxel
STARTED	45
COMPLETED	41
NOT COMPLETED	4

Baseline Characteristics

Arm/Group Title	Carboplatin, Paclitaxel
Arm/Group Description	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.
Overall Participants	58
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	71
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	58 100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	3 5.2%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	3 5.2%
White	52 89.7%
More than one race	0 0%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Prostate-specific Antigen (PSA) Response Rate
Description	PSA response is defined as a decline from the baseline value of >=50% confirmed by a second PSA value 4 or more weeks later.
Time Frame	Evaluated 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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Carboplatin, Paclitaxel
Arm/Group Description	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.
Measure Participants	58
Participants with PSA response	28 48.3%
Participants with no PSA response	30 51.7%

2. Primary Outcome

Title	Time to PSA Progression
Description	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.
Time Frame	Evaluated every 28 days during Treatment Period

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Carboplatin, Paclitaxel
Arm/Group Description	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.
Measure Participants	58
Median (Full Range) [days]	115

3. Secondary Outcome

Title	Objective Response Rate
Description	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.
Time Frame	Evaluated every 12 weeks during Treatment Period

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Carboplatin, Paclitaxel
Arm/Group Description	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.
Measure Participants	53
Participants with Complete Response	1 1.7%
Participants with Partial Response	12 20.7%
Participants with Stable Disease	33 56.9%
Participants with Progression of Disease	7 12.1%

4. Secondary Outcome

Title	Overall Survival Rate
Description	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.
Time Frame	Assessed every two months after completion of study treatment for 4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Carboplatin, Paclitaxel
Arm/Group Description	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.
Measure Participants	58
Deceased	46 79.3%
Alive	1 1.7%
Lost to Follow-up	1 1.7%
Withdrawal by subject	10 17.2%

Adverse Events

Time Frame	Adverse events collected between 11/12/2002 and 08/06/2007, therefore AE reporting period is 4.7 years or 4 years and 9 months, approximately
Adverse Event Reporting Description	Systemic adverse event assessment occurred every 28 days through investigator assessment during treatment period and once within 30 days after last administration of study treatment.
Arm/Group Title	Carboplatin, Paclitaxel
Arm/Group Description	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.
All Cause Mortality
	Carboplatin, Paclitaxel
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Carboplatin, Paclitaxel
	Affected / at Risk (%)	# Events
Total	14/58 (24.1%)
Blood and lymphatic system disorders
Subarachnoid Hemorrhage	1/58 (1.7%)
Cardiac disorders
Deep Verin Thrombosis with Pulmonary Embolism	1/58 (1.7%)
Angina	1/58 (1.7%)
Death secondary to cardiac arrest	1/58 (1.7%)
Gastrointestinal disorders
Dehydration	1/58 (1.7%)
Constipation	1/58 (1.7%)
Gall stones	1/58 (1.7%)
Immune system disorders
Anaphylaxix	1/58 (1.7%)
Infections and infestations
Febrile Neutropenia	2/58 (3.4%)
Metabolism and nutrition disorders
Hyperglycemia and diabetic management	1/58 (1.7%)
Musculoskeletal and connective tissue disorders
back pain	1/58 (1.7%)
Muscle weakness	1/58 (1.7%)
Nervous system disorders
Paresthesia	1/58 (1.7%)
spinal injury; inability to walk or stand ultimately caused death	1/58 (1.7%)
Renal and urinary disorders
Urinary retention with acute hematuria	1/58 (1.7%)
Other (Not Including Serious) Adverse Events
	Carboplatin, Paclitaxel
	Affected / at Risk (%)	# Events
Total	58/ (NaN)
Blood and lymphatic system disorders
Neutropenia	50/58 (86.2%)
anemia	46/58 (79.3%)
Thrombocytopenia	35/58 (60.3%)
Leukopenia	33/58 (56.9%)
Edema, limb	22/58 (37.9%)
hemorrhage pulmonary- nose	11/58 (19%)
Cardiac disorders
hypotension	5/58 (8.6%)
Eye disorders
blurred vision	4/58 (6.9%)
Gastrointestinal disorders
Diarrhea	33/58 (56.9%)
Anorexia	31/58 (53.4%)
Nausea	30/58 (51.7%)
constipation	21/58 (36.2%)
vomiting	16/58 (27.6%)
taste alteration	13/58 (22.4%)
dyspepsia	9/58 (15.5%)
dehydration	5/58 (8.6%)
dry mouth	4/58 (6.9%)
flatulence	3/58 (5.2%)
gastroenteritis	3/58 (5.2%)
mucositis-oral cavity	3/58 (5.2%)
General disorders
Fatigue	44/58 (75.9%)
Insomnia	23/58 (39.7%)
pain, extremity-lower	20/58 (34.5%)
Pain, Not otherwise specified	20/58 (34.5%)
pain, head	11/58 (19%)
fever	9/58 (15.5%)
cold symptoms	7/58 (12.1%)
pain, abdomen	6/58 (10.3%)
sweating	6/58 (10.3%)
pain, chest- non-cardiac	5/58 (8.6%)
sore throat	5/58 (8.6%)
weight loss	5/58 (8.6%)
cachexia	3/58 (5.2%)
pain-urination	3/58 (5.2%)
flu-like syndrome	3/58 (5.2%)
pain, bone	3/58 (5.2%)
pain, neck	3/58 (5.2%)
rigors/chills	3/58 (5.2%)
Immune system disorders
allergic rhinitis	6/58 (10.3%)
allergic reaction	5/58 (8.6%)
Infections and infestations
infection-upper airway not otherwise specified	9/58 (15.5%)
infection- urinary tract not otherwise specified	7/58 (12.1%)
Metabolism and nutrition disorders
hyperglycemia	12/58 (20.7%)
ALT, elevated	5/58 (8.6%)
hypocalcemia	5/58 (8.6%)
hypokalemia	5/58 (8.6%)
alkaline phosphatase, elevated	4/58 (6.9%)
AST, elevated	4/58 (6.9%)
hypoalbuminemia	4/58 (6.9%)
hyperkalemia	3/58 (5.2%)
hyperphosphatemia	3/58 (5.2%)
hypomagnesia	3/58 (5.2%)
hyponatremia	3/58 (5.2%)
Musculoskeletal and connective tissue disorders
pain, back	8/58 (13.8%)
pain, muscle	8/58 (13.8%)
pain, shoulder	8/58 (13.8%)
Muscle weakness	3/58 (5.2%)
Nervous system disorders
Neuropathy-sensory	34/58 (58.6%)
mood alteration-depression	16/58 (27.6%)
dizziness	12/58 (20.7%)
neuropathy-motor	11/58 (19%)
mood alteration- anxiety	7/58 (12.1%)
Renal and urinary disorders
hematuria	11/58 (19%)
urinary frequency	12/58 (20.7%)
Urinary retention	4/58 (6.9%)
Respiratory, thoracic and mediastinal disorders
cough	7/58 (12.1%)
congestion	6/58 (10.3%)
voice changes	3/58 (5.2%)
dyspnea	12/58 (20.7%)
Skin and subcutaneous tissue disorders
Alopecia	45/58 (77.6%)
rash	9/58 (15.5%)
pruritis	5/58 (8.6%)
nail changes	3/58 (5.2%)

Limitations/Caveats

The major weakness of the study is, it is a single-arm non-comparative study. With the small sample size of 58 participants who received treatment, the study does not have the statistical power to make categorical assessments or statements.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The obligations of confidentiality shall apply for a period of 5 yrs beyond termination of Agreement between Sponsor and Investigator,but do not apply to the extent information:is or later becomes known to public;is obtained from a third party without restriction who had a legal right to disclose;is possessed by Investigators,as demonstrated by recipient's written records predating receipt from Sponsor;is required to be disclosed pursuant to a subpoena, law, regulation or other legal proceeding.