Trial Outcomes & Findings for Treating Patients With Metastatic Prostate Cancer Not Responding to Hormone and Chemotherapy (NCT NCT00331344)
NCT ID: NCT00331344
Last Updated: 2017-10-31
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
100 participants
Primary outcome timeframe
Every 3 courses until cancer progression/excessive toxicity or death
Results posted on
2017-10-31
Participant Flow
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.
Participant milestones
| Measure |
Phase I Group I
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
|
Phase I Group II
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
|
Phase I Group III
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
|
Phase I Group IV
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
|
Phase I Group V
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
|
Phase I Group VI
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
|
Phase I Group Va
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
|
Phase I Group VIa
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
|
Phase II
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
|
|---|---|---|---|---|---|---|---|---|---|
|
Phase I
STARTED
|
3
|
3
|
3
|
6
|
6
|
5
|
4
|
6
|
0
|
|
Phase I
COMPLETED
|
3
|
3
|
3
|
5
|
4
|
3
|
4
|
5
|
0
|
|
Phase I
NOT COMPLETED
|
0
|
0
|
0
|
1
|
2
|
2
|
0
|
1
|
0
|
|
Phase II
STARTED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
6
|
52
|
|
Phase II
COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
6
|
48
|
|
Phase II
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
4
|
Reasons for withdrawal
| Measure |
Phase I Group I
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
|
Phase I Group II
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
|
Phase I Group III
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
|
Phase I Group IV
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
|
Phase I Group V
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
|
Phase I Group VI
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
|
Phase I Group Va
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
|
Phase I Group VIa
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
|
Phase II
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
|
|---|---|---|---|---|---|---|---|---|---|
|
Phase I
Adverse Event
|
0
|
0
|
0
|
1
|
2
|
2
|
0
|
1
|
0
|
|
Phase II
Death
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
4
|
Baseline Characteristics
Treating Patients With Metastatic Prostate Cancer Not Responding to Hormone and Chemotherapy
Baseline characteristics by cohort
| Measure |
Treatment (Combination Chemotherapy)
n=88 Participants
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
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
38 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
50 Participants
n=5 Participants
|
|
Age, Continuous
|
66.7 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
88 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
88 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Every 3 courses until cancer progression/excessive toxicity or deathDescriptive 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.
Outcome measures
| Measure |
Treatment (Combination Chemotherapy)
n=56 Participants
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
|
Phase Group II
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
|
Phase I Group III
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
|
Phase I Group IV
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
|
Phase I Group V
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
|
Phase I Group VI
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
|
Phase I Group Va
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
|
Phase I Group VIa
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
|
|---|---|---|---|---|---|---|---|---|
|
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)
|
25 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Every 21 days until cancer progression/excessive toxicity or deathPopulation: Phase I dose escalation study participants
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.
Outcome measures
| Measure |
Treatment (Combination Chemotherapy)
n=36 Participants
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
|
Phase Group II
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
|
Phase I Group III
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
|
Phase I Group IV
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
|
Phase I Group V
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
|
Phase I Group VI
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
|
Phase I Group Va
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
|
Phase I Group VIa
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
|
|---|---|---|---|---|---|---|---|---|
|
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)
|
62 Adverse Events (above threshold)
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Course 1 (first 21 days)Population: Dose escalation safety study (Phase I)
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.
Outcome measures
| Measure |
Treatment (Combination Chemotherapy)
n=3 Participants
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
|
Phase Group II
n=3 Participants
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
|
Phase I Group III
n=3 Participants
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
|
Phase I Group IV
n=6 Participants
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
|
Phase I Group V
n=6 Participants
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
|
Phase I Group VI
n=5 Participants
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
|
Phase I Group Va
n=4 Participants
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
|
Phase I Group VIa
n=6 Participants
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
|
|---|---|---|---|---|---|---|---|---|
|
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).
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
2 Participants
|
2 Participants
|
0 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Every 3 months until cancer progression/excessive toxicity or deathMeasured 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.
Outcome measures
| Measure |
Treatment (Combination Chemotherapy)
n=56 Participants
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
|
Phase Group II
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
|
Phase I Group III
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
|
Phase I Group IV
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
|
Phase I Group V
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
|
Phase I Group VI
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
|
Phase I Group Va
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
|
Phase I Group VIa
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
|
|---|---|---|---|---|---|---|---|---|
|
Time to Progression (Phase II)
|
4.4 months
Interval 3.5 to 5.6
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
Adverse Events
Phase I and Phase II (Cumulative)
Serious events: 19 serious events
Other events: 56 other events
Deaths: 29 deaths
Serious adverse events
| Measure |
Phase I and Phase II (Cumulative)
n=88 participants at risk
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
|
|---|---|
|
Endocrine disorders
Adrenal Insuffiency
|
3.4%
3/88
|
|
Cardiac disorders
Atrial fibrillation
|
3.4%
3/88
|
|
Cardiac disorders
Cardiac ischemia/infarction
|
2.3%
2/88
|
|
Endocrine disorders
Glucose intolerance
|
1.1%
1/88
|
|
Renal and urinary disorders
Infection (Prostate)
|
1.1%
1/88
|
|
Infections and infestations
Infection (limb)
|
1.1%
1/88
|
|
Metabolism and nutrition disorders
Renal Failure
|
2.3%
2/88
|
|
Infections and infestations
Pneumonia
|
1.1%
1/88
|
|
Renal and urinary disorders
Sepsis
|
1.1%
1/88
|
|
Cardiac disorders
Vasovagal episode
|
1.1%
1/88
|
|
Vascular disorders
Deep Vein Thrombosis
|
1.1%
1/88
|
|
Infections and infestations
Methicillin-resistant Staphylococcus aureus
|
1.1%
1/88
|
|
Blood and lymphatic system disorders
Leucocytes
|
3.4%
3/88
|
|
Blood and lymphatic system disorders
Neutrophil count decreased
|
4.5%
4/88
|
|
Blood and lymphatic system disorders
Platelet count decreased
|
1.1%
1/88
|
|
Blood and lymphatic system disorders
Febrile Neutropenia
|
1.1%
1/88
|
|
Metabolism and nutrition disorders
Dehydration
|
1.1%
1/88
|
|
Gastrointestinal disorders
Diarrhea
|
1.1%
1/88
|
Other adverse events
| Measure |
Phase I and Phase II (Cumulative)
n=88 participants at risk
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
|
|---|---|
|
Blood and lymphatic system disorders
Hemoglobin
|
4.5%
4/88
|
|
Blood and lymphatic system disorders
Leucocytes
|
19.3%
17/88
|
|
Blood and lymphatic system disorders
Lymphopenia
|
22.7%
20/88
|
|
Blood and lymphatic system disorders
Neutrophil count decreased
|
13.6%
12/88
|
|
Blood and lymphatic system disorders
Platelet count decreased
|
10.2%
9/88
|
|
Metabolism and nutrition disorders
Alanine aminotransferase increased
|
1.1%
1/88
|
|
Immune system disorders
Allergic Reaction
|
1.1%
1/88
|
|
Endocrine disorders
Adrenal insufficiency
|
9.1%
8/88
|
|
Cardiac disorders
Atrial tachycardia
|
1.1%
1/88
|
|
General disorders
Fatigue
|
18.2%
16/88
|
|
Gastrointestinal disorders
Nausea
|
5.7%
5/88
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
14.8%
13/88
|
|
Nervous system disorders
Dizziness
|
2.3%
2/88
|
|
Gastrointestinal disorders
Dehydration
|
2.3%
2/88
|
|
Infections and infestations
Infection, Colon
|
1.1%
1/88
|
|
Infections and infestations
Pneumonia
|
5.7%
5/88
|
|
Infections and infestations
Infection, Skin
|
4.5%
4/88
|
|
Respiratory, thoracic and mediastinal disorders
Pain, Chest
|
3.4%
3/88
|
|
General disorders
Pain, other
|
2.3%
2/88
|
|
General disorders
Pain, hip
|
1.1%
1/88
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
3.4%
3/88
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
2.3%
2/88
|
|
Metabolism and nutrition disorders
Hyponatremia
|
1.1%
1/88
|
|
Metabolism and nutrition disorders
Hyperbilirubinemia
|
1.1%
1/88
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
1.1%
1/88
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
1.1%
1/88
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
1.1%
1/88
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
1.1%
1/88
|
|
General disorders
Anorexia
|
1.1%
1/88
|
|
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Distress Syndrome
|
1.1%
1/88
|
|
Musculoskeletal and connective tissue disorders
Pain, bone
|
2.3%
2/88
|
|
Gastrointestinal disorders
Diarrhea
|
2.3%
2/88
|
|
Gastrointestinal disorders
Dyspepsia
|
1.1%
1/88
|
|
Blood and lymphatic system disorders
Edema, limb
|
1.1%
1/88
|
|
Infections and infestations
Fever
|
1.1%
1/88
|
|
Endocrine disorders
Hot Flashes
|
1.1%
1/88
|
|
Musculoskeletal and connective tissue disorders
Muscle Weakness
|
2.3%
2/88
|
|
Nervous system disorders
Peripheral Motor Neuropathy
|
2.3%
2/88
|
|
Infections and infestations
Phlebitis
|
1.1%
1/88
|
|
Respiratory, thoracic and mediastinal disorders
Pleural Effusion
|
1.1%
1/88
|
|
Nervous system disorders
Syncope
|
1.1%
1/88
|
|
Nervous system disorders
Taste Alteration
|
2.3%
2/88
|
|
Gastrointestinal disorders
Vomiting
|
3.4%
3/88
|
|
General disorders
Weight Loss
|
2.3%
2/88
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60