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Treating Patients With Metastatic Prostate Cancer Not Responding to Hormone and Chemotherapy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00331344
Recruitment Status : Completed
First Posted : May 31, 2006
Results First Posted : October 31, 2017
Last Update Posted : October 31, 2017
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Study Type Interventional
Study Design Intervention Model: Sequential Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Adenocarcinoma of the Prostate
Recurrent Prostate Cancer
Stage IV Prostate Cancer
Interventions Drug: mitoxantrone hydrochloride
Drug: ixabepilone
Drug: prednisone
Enrollment 100
Recruitment Details Patients (incl. currently followed in these practices, as well as those referred from outside providers) will be screened for interest and eligibility by medical oncologists from UCSF Urologic Oncology Practice CCC, UCSF-VA Medical Cntr, OHSU Cancer Inst., MD Anderson Cancer Cntr, UMich Comprehensive Cancer Cntr and the Portland VA Medical Cntr.
Pre-assignment Details  
Arm/Group Title Phase I Group I Phase I Group II Phase I Group III Phase I Group IV Phase I Group V Phase I Group VI Phase I Group Va Phase I Group VIa Phase II
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Patients receive mitoxantrone hydrochloride 8mg/m2 IV over 30 minutes and ixabepilone 20mg/m2 IV over 3 hours on day 1 and oral prednisone 5mg twice daily on days 1-21. Treatment repeats every 21 days for ≥ 3 courses in the absence of disease progression or unacceptable toxicity.

mitoxantrone hydrochloride: Given IV

ixabepilone: Given IV

prednisone: Given orally

Patients receive mitoxantrone hydrochloride 8mg/m2 IV over 30 minutes and ixabepilone 25mg/m2 IV over 3 hours on day 1 and oral prednisone 5mg twice daily on days 1-21. Treatment repeats every 21 days for ≥ 3 courses in the absence of disease progression or unacceptable toxicity.

mitoxantrone hydrochloride: Given IV

ixabepilone: Given IV

prednisone: Given orally

Patients receive mitoxantrone hydrochloride 10mg/m2 IV over 30 minutes and ixabepilone 25mg/m2 IV over 3 hours on day 1 and oral prednisone 5mg twice daily on days 1-21. Treatment repeats every 21 days for ≥ 3 courses in the absence of disease progression or unacceptable toxicity.

mitoxantrone hydrochloride: Given IV

ixabepilone: Given IV

prednisone: Given orally

Patients receive mitoxantrone hydrochloride 10mg/m2 IV over 30 minutes and ixabepilone 30mg/m2 IV over 3 hours on day 1 and oral prednisone 5mg twice daily on days 1-21. Treatment repeats every 21 days for ≥ 3 courses in the absence of disease progression or unacceptable toxicity.

mitoxantrone hydrochloride: Given IV

ixabepilone: Given IV

prednisone: Given orally

Patients receive mitoxantrone hydrochloride 12mg/m2 IV over 30 minutes and ixabepilone 30mg/m2 IV over 3 hours on day 1 and oral prednisone 5mg twice daily on days 1-21. Treatment repeats every 21 days for ≥ 3 courses in the absence of disease progression or unacceptable toxicity.

mitoxantrone hydrochloride: Given IV

ixabepilone: Given IV

prednisone: Given orally

Patients receive mitoxantrone hydrochloride 12mg/m2 IV over 30 minutes and ixabepilone 35mg/m2 IV over 3 hours on day 1 and oral prednisone 5mg twice daily on days 1-21. Treatment repeats every 21 days for ≥ 3 courses in the absence of disease progression or unacceptable toxicity.

mitoxantrone hydrochloride: Given IV

ixabepilone: Given IV

prednisone: Given orally

Patients receive mitoxantrone hydrochloride 12mg/m2 IV over 30 minutes and ixabepilone 30mg/m2 IV over 3 hours on day 1 and pegfilgrastim 6mg SC on day 2 and oral prednisone 5mg twice daily on days 1-21. Treatment repeats every 21 days for ≥ 3 courses in the absence of disease progression or unacceptable toxicity.

mitoxantrone hydrochloride: Given IV

ixabepilone: Given IV

pegfilgrastim: Given SC

prednisone: Given orally

Patients receive mitoxantrone hydrochloride 12mg/m2 IV over 30 minutes and ixabepilone 35mg/m2 IV over 3 hours on day 1 and pegfilgrastim 6mg SC on day 2 and oral prednisone 5mg twice daily on days 1-21. Treatment repeats every 21 days for ≥ 3 courses in the absence of disease progression or unacceptable toxicity.

mitoxantrone hydrochloride: Given IV

ixabepilone: Given IV

pegfilgrastim: Given SC

prednisone: Given orally

Patients receive mitoxantrone hydrochloride 12mg/m2 IV over 30 minutes and ixabepilone 30mg/m2 IV over 3 hours on day 1 and pegfilgrastim 6mg SC on day 2 and oral prednisone 5mg twice daily on days 1-21. Treatment repeats every 21 days for ≥ 3 courses in the absence of disease progression or unacceptable toxicity.

mitoxantrone hydrochloride: Given IV

ixabepilone: Given IV

pegfilgrastim: Given SC

prednisone: Given orally

Period Title: Phase I
Started 3 3 3 6 6 5 4 6 [1] 0
Completed 3 3 3 5 [2] 4 [3] 3 [3] 4 5 [2] 0
Not Completed 0 0 0 1 2 2 0 1 0
Reason Not Completed
Adverse Event             0             0             0             1             2             2             0             1             0
[1]
1 participant who was enrolled died prior to initiating protocol therapy.
[2]
1 participant reached dose limiting toxicity
[3]
2 participants reached dose limiting toxicity
Period Title: Phase II
Started 0 0 0 0 0 0 0 6 [1] 52 [2]
Completed 0 0 0 0 0 0 0 6 48
Not Completed 0 0 0 0 0 0 0 0 4
Reason Not Completed
Death             0             0             0             0             0             0             0             0             4
[1]
6 patients in Phase I Group VIa continued to the Phase II period.
[2]
Protocol enrollment (63) minus 11 ineligible prior to receiving treatment.
Arm/Group Title Treatment (Combination Chemotherapy)
Hide Arm/Group Description

Patients receive mitoxantrone hydrochloride IV over 30 minutes and ixabepilone IV over 3 hours on day 1 and oral prednisone twice daily on days 1-21. Treatment repeats every 21 days for ≥ 3 courses in the absence of disease progression or unacceptable toxicity.

mitoxantrone hydrochloride: Given IV

ixabepilone: Given IV

prednisone: Given orally

Overall Number of Baseline Participants 88
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 88 participants
<=18 years
0
   0.0%
Between 18 and 65 years
38
  43.2%
>=65 years
50
  56.8%
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 88 participants
66.7
(39 to 83)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 88 participants
Female
0
   0.0%
Male
88
 100.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 88 participants
88
 100.0%
1.Primary Outcome
Title Proportion Responding to Treatment With of the Combination of Ixabepilone and Mitoxantrone Hydrochloride With Prednisone in Hormone Refractory Prostate Cancer Patients Who Have Had Prior Taxane Chemotherapy Based Upon a PSA Decline of > 50% (Phase II)
Hide Description

Descriptive statistics will be calculated to characterize the disease and treatment factors including the proportion responding with a 95% confidence interval. If accrual is completed and more than 15 of 58 patients show > 50% Prostate Specific Antigen (PSA) declines after 3 courses, then the null hypothesis of a 20% response proportion will be rejected. PSA declines for individual patients will be plotted in the form of a waterfall diagram of maximal PSA declines.

58 patients were enrolled for phase II, two were ineligible so 56 patients were analyzed.

Time Frame Every 3 courses until cancer progression/excessive toxicity or death
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment (Combination Chemotherapy)
Hide Arm/Group Description:

Patients receive mitoxantrone hydrochloride 12mg/m2 IV over 30 minutes and ixabepilone 35mg/m2 IV over 3 hours on day 1 and pegfilgrastim 6mg SC on day 2 and oral prednisone twice daily on days 1-21. Treatment repeats every 21 days for ≥ 3 courses in the absence of disease progression or unacceptable toxicity.

mitoxantrone hydrochloride: Given IV

ixabepilone: Given IV

pegfilgrastim: Given SC

prednisone: Given orally

Overall Number of Participants Analyzed 56
Measure Type: Count of Participants
Unit of Measure: Participants
25
  44.6%
2.Primary Outcome
Title Safety of the Combination of Ixabepilone, Mitoxantrone Hydrochloride, and Prednisone in Patients With Hormone-refractory Metastatic Prostate Cancer That Progressed During or After Taxane-based Chemotherapy (Phase I)
Hide Description This study will utilize the Common Terminology Criteria for Adverse Events (CTCAE) v3.0 for adverse event monitoring and reporting. The cumulative grade 3 or higher adverse events for all dose levels are noted below and in the table of adverse events.
Time Frame Every 21 days until cancer progression/excessive toxicity or death
Hide Outcome Measure Data
Hide Analysis Population Description
Phase I dose escalation study participants
Arm/Group Title Phase I Treatment (Groups I-VIa)
Hide Arm/Group Description:

Patients receive mitoxantrone hydrochloride 8-12mg/m2 IV over 30 minutes and ixabepilone 20-35mg/m2 IV over 3 hours on day 1 and oral prednisone twice daily on days 1-21. Patients in groups Va and VIa also received pegfilgrastim 6mg SC on day 2. Treatment repeats every 21 days for ≥ 3 courses in the absence of disease progression or unacceptable toxicity.

mitoxantrone hydrochloride: Given IV

ixabepilone: Given IV

pegfilgrastim: Given SC

prednisone: Given orally

Overall Number of Participants Analyzed 36
Measure Type: Number
Unit of Measure: Adverse Events (above threshold)
62
3.Primary Outcome
Title Dose Limiting Toxicities for Each Dose Level of Ixabepilone, Mitoxantrone Hydrochloride, and Prednisone in Patients With Hormone-refractory Metastatic Prostate Cancer That Progressed During or After Taxane-based Chemotherapy (Phase I).
Hide Description Cohorts of 3 patients will be enrolled at each dose level; if 1 dose limiting toxicity (DLT) is observed then the cohort will be expanded to 6 patients. If a second DLT is observed, the previous dose level will be considered the maximum tolerated dose (MTD). If all observed DLT are due to neuropathy (specific to ixabepilone), then we would consider the previous dose level of Ixabepilone the MTD for that drug, and escalate mitoxantrone hydrochloride as described above to a maximum dose of 12 mg/m^2. Toxicities will be tabulated by grade for each dose cohort and overall for all patients accrued to the phase I study.
Time Frame Course 1 (first 21 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Dose escalation safety study (Phase I)
Arm/Group Title Phase I Group I Phase Group II Phase I Group III Phase I Group IV Phase I Group V Phase I Group VI Phase I Group Va Phase I Group VIa
Hide Arm/Group Description:

Patients receive mitoxantrone hydrochloride 8 mg/m2 IV over 30 minutes and ixabepilone 20mg/m2 IV over 3 hours on day 1 and oral prednisone twice daily on days 1-21. Treatment repeats every 21 days for ≥ 3 courses in the absence of disease progression or unacceptable toxicity.

mitoxantrone hydrochloride: Given IV

ixabepilone: Given IV

prednisone: Given orally

Patients receive mitoxantrone hydrochloride 8 mg/m2 IV over 30 minutes and ixabepilone 25mg/m2 IV over 3 hours on day 1 and oral prednisone twice daily on days 1-21. Treatment repeats every 21 days for ≥ 3 courses in the absence of disease progression or unacceptable toxicity.

mitoxantrone hydrochloride: Given IV

ixabepilone: Given IV

prednisone: Given orally

Patients receive mitoxantrone hydrochloride 10 mg/m2 IV over 30 minutes and ixabepilone 25 mg/m2 IV over 3 hours on day 1 and oral prednisone twice daily on days 1-21. Treatment repeats every 21 days for ≥ 3 courses in the absence of disease progression or unacceptable toxicity.

mitoxantrone hydrochloride: Given IV

ixabepilone: Given IV

prednisone: Given orally

Patients receive mitoxantrone hydrochloride 10 mg/m2 IV over 30 minutes and ixabepilone 30mg/m2 IV over 3 hours on day 1 and oral prednisone twice daily on days 1-21. Treatment repeats every 21 days for ≥ 3 courses in the absence of disease progression or unacceptable toxicity.

mitoxantrone hydrochloride: Given IV

ixabepilone: Given IV

prednisone: Given orally

Patients receive mitoxantrone hydrochloride 12 mg/m2 IV over 30 minutes and ixabepilone 30mg/m2 IV over 3 hours on day 1 and oral prednisone twice daily on days 1-21. Treatment repeats every 21 days for ≥ 3 courses in the absence of disease progression or unacceptable toxicity.

mitoxantrone hydrochloride: Given IV

ixabepilone: Given IV

prednisone: Given orally

Patients receive mitoxantrone hydrochloride 12 mg/m2 IV over 30 minutes and ixabepilone 35mg/m2 IV over 3 hours on day 1 and oral prednisone twice daily on days 1-21. Treatment repeats every 21 days for ≥ 3 courses in the absence of disease progression or unacceptable toxicity.

mitoxantrone hydrochloride: Given IV

ixabepilone: Given IV

prednisone: Given orally

Patients receive mitoxantrone hydrochloride 12 mg/m2 IV over 30 minutes and ixabepilone 30mg/m2 IV over 3 hours on day 1 and pegfilgrastim 6mg SC on day 2 and oral prednisone twice daily on days 1-21. Treatment repeats every 21 days for ≥ 3 courses in the absence of disease progression or unacceptable toxicity.

mitoxantrone hydrochloride: Given IV

ixabepilone: Given IV

pegfilgrastim: Given SC

prednisone: Given orally

Patients receive mitoxantrone hydrochloride 12 mg/m2 IV over 30 minutes and ixabepilone 35mg/m2 IV over 3 hours on day 1 and pegfilgrastim 6mg SC on day 2 and oral prednisone twice daily on days 1-21. Treatment repeats every 21 days for ≥ 3 courses in the absence of disease progression or unacceptable toxicity.

mitoxantrone hydrochloride: Given IV

ixabepilone: Given IV

pegfilgrastim: Given SC

prednisone: Given orally

Overall Number of Participants Analyzed 3 3 3 6 6 5 4 6
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
0
   0.0%
1
  16.7%
2
  33.3%
2
  40.0%
0
   0.0%
1
  16.7%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Phase I Group I, Phase I Group III, Phase I Group IV, Phase I Group V, Phase I Group VI, Phase I Group Va, Phase I Group VIa
Comments Cohorts of 3 patients will be enrolled at each dose level; if 1 dose limiting toxicity (DLT) is observed then the cohort will be expanded to 6 patients. If a second DLT is observed, the previous dose level will be considered the MTD. If all observed DLT are due to neuropathy (specific to ixabepilone), then we would consider the previous dose level of Ixabepilone the MTD for that drug, and escalate mitoxantrone hydrochloride as described above to a maximum dose of 12 mg/m^2.
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Dose Level VIa
Estimated Value 1
Estimation Comments Dose level VIa (mitoxantrone hydrochloride 12 mg/m2 IV over 30 minutes, ixabepilone 30mg/m2 IV over 3 hours on day 1, pegfilgrastim 6mg SC on day 2, oral prednisone twice daily on days 1-21) was determined to be MTD, based on 1 event of DLT at VIa.
4.Secondary Outcome
Title Time to Progression (Phase II)
Hide Description Measured from the start of protocol therapy until RECIST (Response Evaluation Criteria In Solid Tumors Criteria) v1.0 progression. Progression is defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time Frame Every 3 months until cancer progression/excessive toxicity or death
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment (Combination Chemotherapy)
Hide Arm/Group Description:

Patients receive mitoxantrone hydrochloride 12mg/m2 IV over 30 minutes and ixabepilone 35mg/m2 IV over 3 hours on day 1 and pegfilgrastim 6mg SC on day 2 and oral prednisone twice daily on days 1-21. Treatment repeats every 21 days for ≥ 3 courses in the absence of disease progression or unacceptable toxicity.

mitoxantrone hydrochloride: Given IV

ixabepilone: Given IV

pegfilgrastim: Given SC

prednisone: Given orally

Overall Number of Participants Analyzed 56
Median (95% Confidence Interval)
Unit of Measure: months
4.4
(3.5 to 5.6)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Phase I and Phase II (Cumulative)
Hide Arm/Group Description

Patients in the Phase I period receive mitoxantrone hydrochloride 8-12mg/m2 IV over 30 minutes and ixabepilone 20-35mg/m2 IV over 3 hours on day 1 and oral prednisone twice daily on days 1-21. Patients in groups Va and VIa also received pegfilgrastim 6mg SC on day 2. Treatment repeats every 21 days for ≥ 3 courses in the absence of disease progression or unacceptable toxicity.

Patients in Phase II receive mitoxantrone hydrochloride 12mg/m2 IV over 30 minutes and ixabepilone 35mg/m2 IV over 3 hours on day 1 and pegfilgrastim 6mg SC on day 2 and oral prednisone twice daily on days 1-21. Treatment repeats every 21 days for ≥ 3 courses in the absence of disease progression or unacceptable toxicity.

Adverse Events below are reported cumulatively for the entire study.

mitoxantrone hydrochloride: Given IV

ixabepilone: Given IV

pegfilgrastim: Given SC

prednisone: Given orally

All-Cause Mortality
Phase I and Phase II (Cumulative)
Affected / at Risk (%)
Total   29/88 (32.95%) 
Show Serious Adverse Events Hide Serious Adverse Events
Phase I and Phase II (Cumulative)
Affected / at Risk (%)
Total   19/88 (21.59%) 
Blood and lymphatic system disorders   
Leucocytes  3/88 (3.41%) 
Neutrophil count decreased  4/88 (4.55%) 
Platelet count decreased  1/88 (1.14%) 
Febrile Neutropenia  1  1/88 (1.14%) 
Cardiac disorders   
Atrial fibrillation  3/88 (3.41%) 
Cardiac ischemia/infarction  2/88 (2.27%) 
Vasovagal episode  1/88 (1.14%) 
Endocrine disorders   
Adrenal Insuffiency  3/88 (3.41%) 
Glucose intolerance  1/88 (1.14%) 
Gastrointestinal disorders   
Diarrhea  1  1/88 (1.14%) 
Infections and infestations   
Infection (limb)  1/88 (1.14%) 
Pneumonia  1/88 (1.14%) 
Methicillin-resistant Staphylococcus aureus  1/88 (1.14%) 
Metabolism and nutrition disorders   
Renal Failure  2/88 (2.27%) 
Dehydration  1  1/88 (1.14%) 
Renal and urinary disorders   
Infection (Prostate)  1/88 (1.14%) 
Sepsis  1/88 (1.14%) 
Vascular disorders   
Deep Vein Thrombosis  1/88 (1.14%) 
1
Term from vocabulary, CTCAE v3.0
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Phase I and Phase II (Cumulative)
Affected / at Risk (%)
Total   56/88 (63.64%) 
Blood and lymphatic system disorders   
Hemoglobin  4/88 (4.55%) 
Leucocytes  17/88 (19.32%) 
Lymphopenia  20/88 (22.73%) 
Neutrophil count decreased  12/88 (13.64%) 
Platelet count decreased  9/88 (10.23%) 
Edema, limb  1  1/88 (1.14%) 
Cardiac disorders   
Atrial tachycardia  1/88 (1.14%) 
Endocrine disorders   
Adrenal insufficiency  8/88 (9.09%) 
Hot Flashes  1  1/88 (1.14%) 
Gastrointestinal disorders   
Nausea  5/88 (5.68%) 
Dehydration  2/88 (2.27%) 
Diarrhea  1  2/88 (2.27%) 
Dyspepsia  1  1/88 (1.14%) 
Vomiting  1  3/88 (3.41%) 
General disorders   
Fatigue  16/88 (18.18%) 
Pain, other  2/88 (2.27%) 
Pain, hip  1/88 (1.14%) 
Anorexia  1  1/88 (1.14%) 
Weight Loss  1  2/88 (2.27%) 
Immune system disorders   
Allergic Reaction  1/88 (1.14%) 
Infections and infestations   
Infection, Colon  1/88 (1.14%) 
Pneumonia  5/88 (5.68%) 
Infection, Skin  4/88 (4.55%) 
Fever  1  1/88 (1.14%) 
Phlebitis  1  1/88 (1.14%) 
Metabolism and nutrition disorders   
Alanine aminotransferase increased  1/88 (1.14%) 
Hypocalcemia  2/88 (2.27%) 
Hyponatremia  1/88 (1.14%) 
Hyperbilirubinemia  1/88 (1.14%) 
Hyperkalemia  1/88 (1.14%) 
Hypoalbuminemia  1/88 (1.14%) 
Hypophosphatemia  1/88 (1.14%) 
Musculoskeletal and connective tissue disorders   
Pain, bone  1  2/88 (2.27%) 
Muscle Weakness  1  2/88 (2.27%) 
Nervous system disorders   
Peripheral sensory neuropathy  13/88 (14.77%) 
Dizziness  2/88 (2.27%) 
Peripheral Motor Neuropathy  1  2/88 (2.27%) 
Syncope  1  1/88 (1.14%) 
Taste Alteration  1  2/88 (2.27%) 
Respiratory, thoracic and mediastinal disorders   
Pain, Chest  3/88 (3.41%) 
Dyspnea  3/88 (3.41%) 
Hypoxia  1/88 (1.14%) 
Acute Respiratory Distress Syndrome  1  1/88 (1.14%) 
Pleural Effusion  1  1/88 (1.14%) 
1
Term from vocabulary, CTCAE v3.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Andrea Harzstark, M.D.
Organization: Oakland Medical Center
Phone: 510-752-6789
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00331344     History of Changes
Obsolete Identifiers: NCT01648374
Other Study ID Numbers: NCI-2009-00155
055513
CDR0000481121 ( Registry Identifier: PDQ (Physician Data Query) )
N01CM62202 ( U.S. NIH Grant/Contract )
First Submitted: May 30, 2006
First Posted: May 31, 2006
Results First Submitted: June 2, 2017
Results First Posted: October 31, 2017
Last Update Posted: October 31, 2017