Clinical trial NCT00452387: Mitoxantrone, Prednisone Plus Sorafenib in Taxane-Refractory Metastatic Hormone Refractory Prostate Cancer (HRPC)
Official title: Mitoxantrone, Prednisone Plus Sorafenib in Taxane-Refractory Metastatic Hormone Refractory Prostate Cancer (HRPC)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Metastatic Prostate Cancer
Keywords: Prostate Cancer
Lead sponsor: Accelerated Community Oncology Research Network
Sponsor class: OTHER
Collaborators: name: Bayer
First posted: 2007-03-27
Enrollment: 22
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this research study is to determine if the combination of mitoxantrone, prednisone and sorafenib will improve the time to progression of advanced stage metastatic hormone-refractory prostate cancer.

Detailed description: 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.

Eligibility criteria: 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 registration
* 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 trial
* Any condition that impairs patient's ability to swallow whole pills
* Any malabsorption problem

Primary outcomes:
measure: Median Time to Progression (TTP) by Imaging
timeFrame: Radiologic imaging was repeated after every 4 cycles (approximately every 12 weeks) during study treatment.
Secondary outcomes:
measure: Correlation of Biochemical Criteria (PSA, Prostate-specific Antigen) With Objective Imaging
timeFrame: PSA was evaluated on day 1 of every cycle (approximately every 3 weeks) during study treatment. Radiologic imaging was repeated after every 4 cycles (approximately every 12 weeks) during study treatment.
measure: Quality of Life (QoL)
timeFrame: The Patient Care Monitor questionnaire was administered on day 1 of every cycle (approximately every 3 weeks) during study treatment.
measure: Median Overall Survival (OS)
timeFrame: Overall survival was measured from day 1 of treatment until the end of treatment and then every 3 months thereafter until death.
Other outcomes:
Locations:
city: La Verne
country: United States
facility: Wilshire Oncology Medical Group, Inc.
state: California
city: Atlanta
country: United States
facility: Peachtree Hematology Oncology Consultants
state: Georgia
city: Macon
country: United States
facility: Central Georgia Cancer Care
state: Georgia
city: Marietta
country: United States
facility: Northwest Georgia Oncology Centers
state: Georgia
city: Billings
country: United States
facility: Hematology Oncology Centers of the Northern Rockies, PC
state: Montana
city: Columbus
country: United States
facility: Mid-Ohio Oncology/Hematology, Inc.
state: Ohio
city: Lancaster
country: United States
facility: Lancaster Cancer Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Pennsylvania Oncology Hematmology Associates
state: Pennsylvania
city: Memphis
country: United States
facility: The West Clinic
state: Tennessee
city: Chesapeake
country: United States
facility: Cancer Specialists of Tidewater
state: Virginia
Study officials:
affiliation: Peachtree Hematology Oncology Consultants
name: Vasily Assikis, MD
role: PRINCIPAL_INVESTIGATOR
References: