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Mitoxantrone, Prednisone Plus Sorafenib in Taxane-Refractory Metastatic Hormone Refractory Prostate Cancer (HRPC)

Phase 2
18 Years
Not Enrolling
Metastatic Prostate Cancer

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Trial Information

Mitoxantrone, Prednisone Plus Sorafenib in Taxane-Refractory Metastatic Hormone Refractory Prostate Cancer (HRPC)

The primary objective of this study is to test the hypothesis that the combination of
Mitoxantrone, Prednisone and Sorafenib in taxane-refractory patients with metastatic hormone
refractory prostate cancer (mHRPC) will result in an improvement of the median time to
progression (TTP). Since the median (i.e 50% of patients) TTP for Mitoxantrone/Prednisone is
3 months, our hypothesis is that 70% will have not progressed at 3 months with this
investigational combination. Progression will be assessed by radiologic imaging criteria.

The early stopping point is 21 subjects. If 10 or fewer subjects with tumor favorable
response are observed when 21 subjects are accrued then the null hypothesis is accepted and
the trial is terminated. If 16 or more subjects with tumor favorable response are observed
when 21 subjects are accrued then the alternative hypothesis is accepted and the trial is
terminated. The probability of early stopping under the null is 0.51, and under the
alternative is 0.39. If the trial progresses until 42 subjects are evaluated and 24 or more
subjects with favorable response are observed then the null hypothesis is rejected. This
design minimizes the average sample number under the null, which is 31.2.

Inclusion Criteria:

- Voluntary written informed consent

- Histopathologic diagnosis of prostatic adenocarcinoma with evidence of progression
despite adequate castration (testosterone < 50 ng/dL)

- Progressive disease after taxane-based chemotherapy (docetaxel or paclitaxel, single
agent or combination regimens, weekly or every 21 day schedules)

- Patients who discontinued taxane- based chemotherapy because of toxicity will be
eligible as long as there is evidence of progressive disease

- Minimum of 4 weeks period from last chemotherapy infusion to registration (this does
not apply to steroid use which is permitted). Estramustine needs to be discontinued
at least 6 weeks prior to first day of treatment on protocol

- A minimum of 4 weeks off bicalutamide, nilutamide, megestrol acetate ketoconazole,
diethylstilbestrol (DES). Minimum of 2 weeks off flutamide

- Reductase inhibitors will be allowed if initiated at least 2 months prior to

- No concurrent investigational therapy

- Complementary and Alternative Medicine (CAM) products will be permitted as long as
patients have been receiving them for at least 2 months. Initiation of new CAM
products while on protocol will be discouraged.

- Ongoing androgen deprivation therapy (orchiectomy, gonadotropin-releasing hormone
(GnRH) agonist or antagonist)

- Adequate bone marrow, liver and renal function as assessed by the following:

- Hemoglobin ≥ 9.0 g/dl

- Absolute neutrophil count (ANC) ≥ 1,500/mm3

- Platelet count ≥ 100,000/mm3

- Total bilirubin ≤ 1.5 times upper limit of normal (ULN)

- ALT and AST ≤ 2.5 times the ULN ( ≤ 5 x ULN for patients with liver involvement)

- Creatinine ≤ 1.5 times the ULN

- International normalized ratio (INR) < 1.5 or a Prothrombin (PT)/Partial
thromboplastin time (PTT) within normal limits. Patients receiving anti-coagulation
treatment with an agent such as warfarin or heparin may be allowed to participate.
For patients on warfarin, the INR should be measured prior to initiation of sorafenib
and monitored at least weekly, or as defined by the local standard of care, until INR
is stable.

- ECOG performance status ≤ 2

- Baseline left ventricular ejection fraction (LVEF) ≥ 50%

- Life expectancy ≥ 3 months

- Patients must agree to use adequate contraception prior to study entry, during the
study and for at least three months after the last administration of sorafenib

Exclusion Criteria:

- More than one line of prior cytotoxic chemotherapy in the metastatic setting,
previous adjuvant chemotherapy will be allowed

- No active malignancy other than prostate cancer (except non-melanoma skin cancer)
within 5 years of enrollment

- Known brain metastases

- Cardiac disease: Congestive heart failure > class II New York Heart Association
(NYHA). Patients must not have unstable angina or new onset angina (began within the
last 3 months) or myocardial infarction within the past 6 months

- Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy

- Uncontrolled hypertension

- Active clinically serious infection > Common Terminology Criteria for Adverse Events
(CTCAE) Grade 2

- Thrombolic or embolic events such as a cerebrovascular accident including transient
ischemic attacks within the past 6 months

- Pulmonary hemorrhage/bleeding event ≥ CTCAE Grade 2 within 4 weeks of first dose of
study drug

- Any other hemorrhage/bleeding event ≥ CTCAE Grade 3 within 4 weeks of first dose of
study drug

- Poorly controlled hyperglycemia

- Treatment with radiotherapy within 4 weeks or treatment with radiopharmaceuticals
within past 8 weeks

- Patient has received other investigational drugs within 14 days before enrollment

- Serious medical or psychiatric illness likely to interfere with participation in this
clinical study

- Serious non-healing wound or ulcer

- Evidence or history of bleeding diathesis or coagulopathy

- Use of St. John's Wort or rifampin

- Known or suspected allergy to sorafenib or any agent given in the course of this

- Any condition that impairs patient's ability to swallow whole pills

- Any malabsorption problem

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Median Time to Progression (TTP) by Imaging

Outcome Description:

Time to progression is defined as the time from treatment start until objective tumor progression. The median time to progression is the parameter used to describe TTP.

Outcome Time Frame:

Radiologic imaging was repeated after every 4 cycles (approximately every 12 weeks) during study treatment.

Safety Issue:


Principal Investigator

Vasily Assikis, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Peachtree Hematology Oncology Consultants


United States: Institutional Review Board

Study ID:




Start Date:

May 2007

Completion Date:

January 2009

Related Keywords:

  • Metastatic Prostate Cancer
  • Prostate Cancer
  • Prostatic Neoplasms



Wilshire Oncology Medical Group, Inc. Rancho Cucamonga, California  91730
Mid-Ohio Oncology/Hematology, Inc. Columbus, Ohio  43222
Lancaster Cancer Center Lancaster, Pennsylvania  17604
The West Clinic Memphis, Tennessee  38120
Northwest Georgia Oncology Centers Marietta, Georgia  30060
Hematology Oncology Centers of the Northern Rockies, PC Billings, Montana  59101
Cancer Specialists of Tidewater Chesapeake, Virginia  
Central Georgia Cancer Care Macon, Georgia  31201
Peachtree Hematology Oncology Consultants Atlanta, Georgia  30309
Pennsylvania Oncology Hematmology Associates Philadelphia, Pennsylvania  19106